Nothing Special   »   [go: up one dir, main page]

CN103555722B - 利用不对称双链rna特异性抑制kras的方法和组合物 - Google Patents

利用不对称双链rna特异性抑制kras的方法和组合物 Download PDF

Info

Publication number
CN103555722B
CN103555722B CN201310485274.XA CN201310485274A CN103555722B CN 103555722 B CN103555722 B CN 103555722B CN 201310485274 A CN201310485274 A CN 201310485274A CN 103555722 B CN103555722 B CN 103555722B
Authority
CN
China
Prior art keywords
seq
kras
target
rna
chain
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Active
Application number
CN201310485274.XA
Other languages
English (en)
Other versions
CN103555722A (zh
Inventor
B·D·布朗
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Dicerna Pharmaceuticals Inc
Original Assignee
Dicerna Pharmaceuticals Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from PCT/US2009/005214 external-priority patent/WO2010033225A2/en
Priority claimed from US12/642,371 external-priority patent/US8513207B2/en
Priority claimed from US12/642,264 external-priority patent/US20100173973A1/en
Priority claimed from US12/704,256 external-priority patent/US20100249214A1/en
Application filed by Dicerna Pharmaceuticals Inc filed Critical Dicerna Pharmaceuticals Inc
Publication of CN103555722A publication Critical patent/CN103555722A/zh
Application granted granted Critical
Publication of CN103555722B publication Critical patent/CN103555722B/zh
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • C12N15/1135Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against oncogenes or tumor suppressor genes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/70Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088Compounds having three or more nucleosides or nucleotides
    • A61K31/713Double-stranded nucleic acids or oligonucleotides
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K48/00Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
    • A61K48/005Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy characterised by an aspect of the 'active' part of the composition delivered, i.e. the nucleic acid delivered
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • A61P35/02Antineoplastic agents specific for leukemia
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07HSUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H21/00Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids
    • C07H21/02Compounds containing two or more mononucleotide units having separate phosphate or polyphosphate groups linked by saccharide radicals of nucleoside groups, e.g. nucleic acids with ribosyl as saccharide radical
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N15/00Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
    • C12N15/09Recombinant DNA-technology
    • C12N15/11DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
    • C12N15/113Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/10Type of nucleic acid
    • C12N2310/14Type of nucleic acid interfering N.A.
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/32Chemical structure of the sugar
    • C12N2310/3212'-O-R Modification
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/32Chemical structure of the sugar
    • C12N2310/3222'-R Modification
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/34Spatial arrangement of the modifications
    • C12N2310/342Hemimers, i.e. of the type ====----
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/30Chemical structure
    • C12N2310/34Spatial arrangement of the modifications
    • C12N2310/344Position-specific modifications, e.g. on every purine, at the 3'-end
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2310/00Structure or type of the nucleic acid
    • C12N2310/50Physical structure
    • C12N2310/53Physical structure partially self-complementary or closed
    • C12N2310/533Physical structure partially self-complementary or closed having a mismatch or nick in at least one of the strands
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12NMICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N2320/00Applications; Uses
    • C12N2320/50Methods for regulating/modulating their activity
    • C12N2320/52Methods for regulating/modulating their activity modulating the physical stability, e.g. GC-content

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Genetics & Genomics (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Biomedical Technology (AREA)
  • Biotechnology (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Zoology (AREA)
  • General Engineering & Computer Science (AREA)
  • Wood Science & Technology (AREA)
  • Biophysics (AREA)
  • Plant Pathology (AREA)
  • Physics & Mathematics (AREA)
  • Microbiology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Oncology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Epidemiology (AREA)
  • Hematology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Micro-Organisms Or Cultivation Processes Thereof (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Saccharide Compounds (AREA)

Abstract

本发明涉及通过使用具有不对称末端结构的Dicer底物siRNA(DsiRNA)试剂而用于降低KRAS靶RNA和蛋白质水平的化合物、组合物和方法。

Description

利用不对称双链RNA特异性抑制KRAS的方法和组合物
本发明为分案申请,原母案的申请号为201080024105.0,原案国际申请日为2010年4月5日,进入中国国家阶段日期为2011年11月30日,原案名称为:利用不对称双链RNA特异性抑制KRAS的方法和组合物。
相关申请的交叉引用
本申请依据美国法典第35篇第119条(e)款要求以下申请的优先权和权益:2009年4月3日提交的美国临时专利申请No.61/166,559;2009年4月3日提交的美国临时专利申请No.61/166,578;2009年4月30日提交的美国临时专利申请No.61/174,279;2009年4月30日提交的美国临时专利申请No.61/174,306;2009年11月3日提交的美国临时专利申请No.61/257,810;和2009年11月3日提交的美国临时专利申请No.61/257,820。本申请还要求以下申请的优先权:2010年2月11日提交的美国专利申请No.12/704,256;2009年12月18日提交的美国专利申请No.12/642,371;2009年12月18日提交的美国专利申请No.12/646,404;2009年12月18日提交的美国专利申请No.12/642,264;和2009年9月17日提交的PCT申请No.PCT/US2009/005214。本申请依据美国法典第35篇第119条(e)款要求以下申请的优先权和权益:2009年6月3日提交的美国临时专利申请No.61/183,815;2009年6月3日提交的美国临时专利申请No.61/183,818;2009年6月5日提交的美国临时专利申请No.61/184,735;2009年12月11日提交的美国临时专利申请No.61/285,925;和2010年3月1日提交的美国临时专利申请No.61/309,266。上述申请完整教导以引用的方式并入本文。
发明领域
本发明涉及用于研究、诊断和治疗响应KRAS基因表达和/或活性调节的特征、疾病和病况的化合物、组合物和方法。本发明还涉及与某些特征、疾病和病况有关的化合物、组合物和方法,这些特征、疾病和病况响应KRAS基因表达通路或介导此类特征、疾病和病况的维持或发展的其它细胞过程中所涉及基因的表达和/或活性调节。具体而言,本发明涉及能够由Dicer酶加工的小核酸分子,例如Dicer底物siRNA(DsiRNA),其能够介导针对KRAS基因表达的RNA干扰(RNAi)。这些抗KRAS DsiRNA可用于例如提供用于治疗可响应受试者体内KRAS调节的特征、疾病和病况(例如癌症和/或其它增生性疾病、病症或病况)的组合物。
发明背景
Ras信号传导调控异常会导致肿瘤生长和转移(Goodsell DS.Oncologist4:263-4)。据估计,所有人肿瘤中有20%-25%含有Ras激活突变;而且在特定肿瘤类型中,这一数字高达90%(Downward J.Nat Rev Cancer,3:11-22)。因此,Ras基因家族的成员是对于癌症治疗设计值得关注的分子靶。
三个人RAS基因编码高度相关的188至189个氨基酸的蛋白质,命名为H-Ras、N-Ras以及K-Ras4A(KRAS同种型a)和K-Ras4B(KRAS同种型b;这两种Kras蛋白由替代性基因剪接产生)。Ras蛋白可充当二元分子开关,用以控制细胞内信号传导网络。Ras调控的信号通路控制例如肌动蛋白细胞骨架完整性、增殖、分化、细胞粘附、细胞凋亡和细胞迁移等过程。在癌症中,Ras和Ras相关蛋白通常失调,导致侵袭和转移增加以及细胞凋亡减少。Ras激活许多通路,但对于肿瘤发生来说特别重要的一条通路似乎是丝裂原激活蛋白(MAP)激酶,这些MAP激酶本身会将信号向下游传导到其它蛋白激酶和基因调控蛋白(Lodish等,MolecularCell Biology(第4版).San Francisco:W.H.Freeman,第25章,“Cancer”)。
具有链长度为25至35个核苷酸的双链RNA(dsRNA)试剂曾被描述为哺乳动物细胞中靶基因表达的有效抑制剂(Rossi等,美国专利申请No.2005/0244858和US2005/0277610)。认为这种长度的dsRNA试剂由RNA干扰(RNAi)通路的Dicer酶加工,使得此类试剂被称为“Dicer底物siRNA”(“DsiRNA”)试剂。先前也曾描述过DsiRNA试剂的其它修饰结构(Rossi等,美国专利申请No.2007/0265220)。
发明概述
本发明涉及含有双链RNA(“dsRNA”)的组合物及其制备方法。本发明的dsRNA能够在体外或哺乳动物受试者体内降低细胞中靶KRas基因的表达。更具体来说,本发明涉及优选的Dicer底物siRNA(“DsiRNA”),其结构和修饰模式经过优化以用作有效且高效的KRAS抑制剂,任选地具有延长的抑制作用持续时间。此类DsiRNA中绝大多数的靶特异性抑制效力和功效相对于针对相同靶RNA的21个核苷酸的siRNA都意外地增强。虽然不希望受理论束缚,但这一增强的活性可能反映了DsiRNA试剂的固有益处,该DsiRNA试剂在RNAi通路中处于较短siRNA试剂参与RNAi通路的点的上游的点处参与该通路。
一方面,本发明提供一种分离的双链核糖核酸(dsRNA),其包含第一和第二核酸链以及具有至少25个碱基对的双链体区,其中所述dsRNA的第二条链在其3'末端包含1-5个单链核苷酸,其中当将所述双链核酸引入哺乳动物细胞中时,该第二寡核苷酸链沿第二寡核苷酸链长度的至少19个核苷酸且最多35个核苷酸与选自由SEQ ID NO:141-186组成的组的靶KRAS cDNA序列充分互补,以降低KRAS靶基因表达。
在一个实施方案中,从第一寡核苷酸链3'末端的第一个核苷酸(1位)开始,用经过修饰的核苷酸取代1位、2位和/或3位。在某些实施方案中,第一条链3'末端的经过修饰的核苷酸残基是脱氧核糖核苷酸、无环核苷酸或荧光分子。在相关实施方案中,第一寡核苷酸链3'末端的1位是脱氧核糖核苷酸。
在另一实施方案中,第一条链的3'末端与第二条链的5'末端形成平端。
在另一实施方案中,第一条链的长度为25个核苷酸,而第二条链的长度为27个核苷酸。
在一个实施方案中,第二条链包括序列SEQ ID NO:11-50和135-140。
在另一实施方案中,第一条链包括序列SEQ ID NO:5、8和91-134。
在另一实施方案中,dsRNA包括第一条链/第二条链的序列对,该序列对是SEQ IDNO:5/SEQ ID NO:14、SEQ ID NO:8/SEQ ID NO:43、SEQ ID NO:132/SEQ ID NO:138、SEQ IDNO:91/SEQ ID NO:11、SEQ ID NO:129/SEQ ID NO:135、SEQ ID NO:92/SEQ ID NO:12、SEQID NO:130/SEQ ID NO:136、SEQ ID NO:93/SEQ ID NO:13、SEQ ID NO:131/SEQ ID NO:137、SEQ ID NO:94/SEQ ID NO:15、SEQ ID NO:133/SEQ ID NO:139、SEQ ID NO:95/SEQ IDNO:16、SEQ ID NO:96/SEQ ID NO:17、SEQ ID NO:97/SEQ ID NO:18、SEQ ID NO:98/SEQ IDNO:19、SEQ ID NO:99/SEQ ID NO:20、SEQ ID NO:100/SEQ ID NO:21、SEQ ID NO:101/SEQID NO:22、SEQ ID NO:102/SEQ ID NO:23、SEQ ID NO:103/SEQ ID NO:24、SEQ ID NO:104/SEQ ID NO:25、SEQ ID NO:105/SEQ ID NO:26、SEQ ID NO:106/SEQ ID NO:27、SEQ ID NO:107/SEQ ID NO:28、SEQ ID NO:108/SEQ ID NO:29、SEQ ID NO:109/SEQ ID NO:30、SEQ IDNO:110/SEQ ID NO:31、SEQ ID NO:111/SEQ ID NO:32、SEQ ID NO:112/SEQ ID NO:33、SEQID NO:113/SEQ ID NO:34、SEQ ID NO:114/SEQ ID NO:35、SEQ ID NO:115/SEQ ID NO:36、SEQ ID NO:116/SEQ ID NO:37、SEQ ID NO:117/SEQ ID NO:38、SEQ ID NO:118/SEQ IDNO:39、SEQ ID NO:119/SEQ ID NO:40、SEQ ID NO:134/SEQ ID NO:140、SEQ ID NO:120/SEQ ID NO:41、SEQ ID NO:121/SEQ ID NO:42、SEQ ID NO:122/SEQ ID NO:44、SEQ ID NO:123/SEQ ID NO:45、SEQ ID NO:124/SEQ ID NO:46、SEQ ID NO:125/SEQ ID NO:47、SEQ IDNO:126/SEQ ID NO:48、SEQ ID NO:127/SEQ ID NO:49或SEQ ID NO:128/SEQ ID NO:50。
在一个实施方案中,第一条链和第二条链各自的长度是至少26个核苷酸。
在另一实施方案中,3'突出的核苷酸包括经过修饰的核苷酸。任选地,3'突出的经过修饰的核苷酸为2'-O-甲基核糖核苷酸。在相关实施方案中,3'突出的所有核苷酸都是经过修饰的核苷酸。
在另一实施方案中,第一和第二寡核苷酸链中的一者或两者包含5'磷酸。
在另一实施方案中,dsRNA的经过修饰的核苷酸残基是2'-O-甲基、2'-甲氧基乙氧基、2'-氟、2'-烯丙基、2'-O-[2-(甲基氨基)-2-氧代乙基]、4'-硫代、4'-CH2-O-2'-桥、4'-(CH2)2-O-2'-桥、2'-LNA、2'-氨基或2'-O-(N-甲基氨基甲酸酯)。
在一个实施方案中,dsRNA的3'突出的长度为1-3个核苷酸。任选地,该3'突出的长度为1-2个核苷酸。在相关实施方案中,3'突出的长度是两个核苷酸,并且3'突出的经过修饰的核苷酸是2'-O-甲基修饰的核糖核苷酸。
在另一实施方案中,从第二条链的与第一寡核苷酸链5'末端核苷酸残基互补的核苷酸残基开始,第二寡核苷酸链包含交替的经过修饰和未修饰的核苷酸残基。在另一实施方案中,从第二条链的与第一寡核苷酸链5'末端核苷酸残基互补的核苷酸残基开始,第二寡核苷酸链在从18位至第二寡核苷酸链5'末端的所有位置包含未修饰的核苷酸残基。
在另一实施方案中,第一条链和第二条链各自的长度为至少26个且最多30个核苷酸。
在一个实施方案中,dsRNA在细胞中由Dicer内源性裂解。
在另一实施方案中,在细胞环境中,足以降低靶基因表达的分离的双链核酸的量是1纳摩尔或更低、200皮摩尔或更低、100皮摩尔或更低、50皮摩尔或更低、20皮摩尔或更低、10皮摩尔或更低、5皮摩尔或更低、2皮摩尔或更低或1皮摩尔或更低。
在另一实施方案中,当在体外于哺乳动物细胞中测定时,在细胞环境中有效浓度为1纳摩尔或更低、200皮摩尔或更低、100皮摩尔或更低、50皮摩尔或更低、20皮摩尔或更低、10皮摩尔或更低、5皮摩尔或更低、2皮摩尔或更低或者1皮摩尔或更低时,分离的dsRNA在降低靶KRAS基因表达方面比针对靶KRAS cDNA的同样至少19个核苷酸的分离的21mersiRNA具有更强的效力。
在另一实施方案中,当将分离的dsRNA引入哺乳动物细胞中时,该双链核酸与靶KRAS cDNA序列充分互补,以使KRAS靶基因表达降低至少10%、至少50%、至少80-90%、至少95%、至少98%或至少99%。
在另一实施方案中,第一条链与第二条链通过化学连接子连结。在相关实施方案中,第一条链的3'末端与第二条链的5'末端通过化学连接子连结。
在一个实施方案中,用引导Dicer裂解定向的经过修饰的核苷酸取代第二条链或第一条链的核苷酸。
在另一实施方案中,dsRNA具有的经过修饰的核苷酸是脱氧核糖核苷酸、双脱氧核糖核苷酸、无环核苷酸、3'-脱氧腺苷(虫草素(cordycepin))、3'-叠氮基-3'-脱氧胸苷(AZT)、2',3'-双脱氧肌苷(ddI)、2',3'-双脱氧-3'-硫代胞苷(3TC)、2',3'-双脱氢-2',3'-双脱氧胸苷(d4T)、3'-叠氮基-3'-脱氧胸苷(AZT)的单磷酸核苷酸、2',3'-双脱氧-3'-硫代胞苷(3TC)和2',3'-双脱氢-2',3'-双脱氧胸苷(d4T)的单磷酸核苷酸、4-硫尿嘧啶、5-溴尿嘧啶、5-碘尿嘧啶、5-(3-氨基烯丙基)-尿嘧啶、2'-O-烷基核糖核苷酸、2'-O-甲基核糖核苷酸、2'-氨基核糖核苷酸、2'-氟核糖核苷酸或锁核酸。
在另一实施方案中,dsRNA具有磷酸酯、硫代磷酸酯或磷酸三酯磷酸骨架修饰。
在一个实施方案中,本发明提供一种用于降低哺乳动物细胞中靶KRAS基因表达的方法,该方法包括使哺乳动物细胞在体外与足以降低细胞中靶KRAS基因表达的量的所述分离的dsRNA接触。
在一个实施方案中,将靶KRAS基因表达降低至少10%、至少50%或至少80-90%。在另一实施方案中,在细胞与dsRNA接触后至少8天,将靶KRASmRNA水平降低至少90%。在另一实施方案中,在细胞与dsRNA接触后至少10天,将KRAS mRNA水平降低至少70%。
在另一实施方案中,本发明提供一种通过对哺乳动物施用足以降低哺乳动物体内靶KRAS基因表达的量的所述分离的dsRNA来降低哺乳动物体内靶KRAS基因表达的方法。
在一个实施方案中,分离的dsRNA以每天每公斤哺乳动物1微克至5毫克、每公斤100微克至0.5毫克、每公斤0.001至0.25毫克、每公斤0.01至20微克、每公斤0.01至10微克、每公斤0.10至5微克或每公斤0.1至2.5微克的剂量施用。
在另一实施方案中,当在体外于哺乳动物细胞中测定时,在细胞环境中有效浓度为1纳摩尔或更低时,分离的dsRNA在降低靶KRAS基因表达方面比针对靶KRAS cDNA的同样至少19个核苷酸的分离的21mer siRNA的具有更强的效力。
在另一实施方案中,施用步骤包括静脉内注射、肌肉内注射、腹腔内注射、输注、皮下注射、透皮递送、气雾剂递送、直肠递送、阴道递送、局部递送、口服递送或吸入递送。
在另一实施方案中,本发明提供一种通过使细胞与足以抑制所述细胞生长的量的所述分离的dsRNA接触来选择性抑制细胞生长的方法。
在一个实施方案中,所述细胞是受试者的肿瘤细胞。任选地,所述细胞为体外肿瘤细胞。在相关实施方案中,所述细胞是人细胞。
在另一实施方案中,本发明提供一种制剂,其包含所述分离的dsRNA,其中当在体外将dsRNA引入哺乳动物细胞中时,dsRNA的存在量可以将靶KRAS RNA水平有效降低至少10%、至少50%或至少80-90%,且其中当在体外于哺乳动物细胞中测定时,在细胞环境中有效浓度为1纳摩尔或更低时,dsRNA在降低靶KRAS RNA水平方面比针对靶KRAS cDNA的同样至少19个核苷酸的分离的21mer siRNA具有更强的效力。
在一个实施方案中,在细胞环境中,有效量是1纳摩尔或更低、200皮摩尔或更低、100皮摩尔或更低、50皮摩尔或更低、20皮摩尔或更低、10皮摩尔或更低、5皮摩尔或更低、2皮摩尔或更低或者1皮摩尔或更低。
在另一实施方案中,本发明提供一种制剂,其包含所述分离的dsRNA,其中当将dsRNA引入哺乳动物受试者的细胞中时,dsRNA的存在量将靶RNA水平有效降低至少10%、至少50%或至少80-90%,且其中当在体外于哺乳动物细胞中测定时,在细胞环境中有效浓度为1纳摩尔或更低时,dsRNA在降低靶KRAS RNA水平方面比针对靶KRAS cDNA的同样至少19个核苷酸的分离的21mer siRNA具有更强的效力。
在一个实施方案中,有效量是每天每公斤受试者1微克至5毫克、每公斤100微克至0.5毫克、每公斤0.001至0.25毫克、每公斤0.01至20微克、每公斤0.01至10微克、每公斤0.10至5微克或每公斤0.1至2.5微克的剂量。
在另一实施方案中,本发明提供一种哺乳动物细胞,其含有所述分离的dsRNA。
本发明的另一实施方案提供一种药物组合物,其包含所述分离的dsRNA和药学上可接受的载体。本发明另一实施方案提供一种试剂盒,该试剂盒具有所述分离的dsRNA和其使用说明。
另一方面,本发明提供一种具有KRAS抑制活性的组合物,该组合物实质上由分离的双链核糖核酸(dsRNA)组成,该分离的dsRNA包含第一和第二核酸链以及至少25个碱基对的双链体区,其中所述dsRNA的第二条链在其3'末端包含1-5个单链核苷酸,其中当将所述双链核酸引入哺乳动物细胞中时,第二寡核苷酸链沿第二寡核苷酸链长度的至少19个核苷酸且最多35个核苷酸与选自由SEQ ID NO:141-186组成的组的靶KRAS cDNA序列充分互补,以降低KRAS靶基因表达。
在另一方面中,本发明提供一种分离的双链核糖核酸(dsRNA),该dsRNA包含第一和第二核酸链以及具有至少25个碱基对的双链体区,其中所述dsRNA的第二条链在其3'末端包含1-5个单链核苷酸,其中当将双链核酸引入哺乳动物细胞中时,第二寡核苷酸链沿第二寡核苷酸链长度的至少19个核苷酸且最多35个核苷酸与选自由SEQ ID NO:1595-2297和3704-4406组成的组的靶KRAS cDNA序列充分互补,以降低KRAS靶基因表达。
在一个实施方案中,第二条链包括序列SEQ ID NO:189-891和2298-3000。
在另一实施方案中,第一条链包括序列SEQ ID NO:892-1594和3001-3703。
在另一实施方案中,dsRNA包括选自由表4-5中所示的DsiRNA试剂组成的组的DsiRNA试剂。
另一方面,本发明提供一种具有KRAS抑制活性的组合物,该组合物实质上由分离的双链核糖核酸(dsRNA)组成,该分离的dsRNA包含第一和第二核酸链以及具有至少25个碱基对的双链体区,其中dsRNA的第二条链在其3'末端包含1-5个单链核苷酸,其中当将所述双链核酸引入哺乳动物细胞中时,第二寡核苷酸链沿第二寡核苷酸链长度的至少19个核苷酸且最多35个核苷酸与选自由SEQ ID NO:1595-2297和3704-4406组成的组的靶KRAS cDNA序列充分互补,由此降低KRAS靶基因表达。
附图简述
示出靶向KRAS RNA中的本文称为“KRAS-355”靶位点的位点的示例性DsiRNA试剂的结构。与所示的21mer siRNA构建体相比较测试25/27mer和27/27mer DsiRNA试剂(任选地,具有平端/断裂(fray)设计)的KRas抑制功效。大写字母=未修饰的RNA,小写字母=DNA,粗体=错配碱基对核苷酸;箭头表示预计的Dicer酶裂解位点;虚线表示对应于靶KRas序列内预计的Argonaute2(Ago2)裂解位点的有义链(上链)序列。
示出图1所示试剂当以1纳摩尔的浓度转化到培养的细胞中时的抗KRAS抑制功效。“优化的”=图1中的25/27mer DsiRNA和21mer siRNA;平端/平端和平端/断裂试剂如图1所示;“Veh”=媒介物处理的对照物;“Un”=未处理的对照物。
示出图1所示试剂当以100皮摩尔的浓度转化到培养的细胞中时的抗KRAS抑制功效。“优化的”=图1中的25/27mer DsiRNA和21mer siRNA;平端/平端和平端/断裂试剂如图1所示;“Veh”=媒介物处理的对照物;“Un”=未处理的对照物。
示出靶向KRAS RNA中的本文称为“KRAS-940”靶位点的位点的示例性DsiRNA试剂的结构。测试25/27mer和27/27mer DsiRNA试剂(任选地,具有平端/断裂设计)的KRAS抑制功效,并与所示的21mer siRNA构建体相比较。大写字母=未修饰的RNA,小写字母=DNA,粗体=错配碱基对核苷酸;箭头表示预计的Dicer酶裂解位点;虚线表示对应于靶KRAS序列内预计的Argonaute2(Ago2)裂解位点的有义链(上链)序列。
示出图4所示试剂当以1纳摩尔的浓度转化到培养的细胞中时的抗KRAS抑制功效。“优化的”=图4中的25/27mer DsiRNA和21mer siRNA;平端/平端和平端/断裂试剂如图4所示;“Veh”=媒介物处理的对照物;“Un”=未处理的对照物。
示出图4所示试剂当以100皮摩尔的浓度转化到培养的细胞中时的抗KRAS抑制功效。“优化的”=图4中的25/27mer DsiRNA和21mer siRNA;平端/平端和平端/断裂试剂如图4所示;“Veh”=媒介物处理的对照物;“Un”=未处理的对照物。
示出测试的DsiRNA和其Dicer加工产物与针对相同的确切KRAS靶序列的同源21mer siRNA的示意性比较。2'-O-甲基修饰以空心圆指示;实心圆指示脱氧核糖核苷酸;实心三角形指示25/27mer试剂内的Dicer酶裂解位点;空心三角形指示反义链上对应于靶RNA内的Argonaute2(Ago2)裂解位点的位置。当与其同源siRNA试剂相比较时,40种测试的DsiRNA试剂的这些位点相同。
示出抗KRAS DsiRNA25/27mer与其同源21mer siRNA之间抑制功效的比较图。该图是按25/27mer DsiRNA试剂针对KRAS靶基因的抑制%的等级次序布置。箭头指示观察的DsiRNA试剂与相应siRNA试剂之间功效差异。正方形指示siRNA抑制结果;圆圈指示DsiRNA抑制结果。
示出按DsiRNA试剂与其同源siRNA之间抑制作用差异量的等级次序布置的抑制结果的图。以5nM(实心方形)和1nM(实心三角形)施用后24小时时以及以5nM(空心方形)和1nM(空心三角形)施用后48小时时测试DsiRNA和siRNA。实心区指示观察到DsiRNA与同源siRNA之间存在统计学显著差异的试剂。对于40种测试的抗KRAS DsiRNA试剂中的26种,与40种siRNA试剂中仅6种优于DsiRNA试剂形成相比,观察到统计学显著的DsiRNA优越性。
示出所观察的所述人KRAS靶向的DsiRNA的IC-50曲线。
示出所观察的所述DsiRNA的人KRAS抑制功效的柱形图。“P1”指示第1阶段,而“P2”指示第2阶段。在第1阶段中,在HeLa细胞环境中以1nM测试DsiRNA。在第2阶段中,在HeLa细胞环境中以1nM和0.1nM(以0.1nM进行两次重复实验)测试DsiRNA。单独条形表示三次重复中观察到的平均人KRAS水平,同时示出了标准误差。将人KRAS水平针对HPRT和SFRS9水平归一化。
示出所观察的所述DsiRNA的小鼠KRAS抑制功效的柱形图。P1”指示第1阶段,而“P2”指示第2阶段。在第1阶段中,在小鼠Hepa1-6细胞中以1nM测试DsiRNA。在第2阶段中,在小鼠Hepa1-6细胞中以1nM和0.1nM(以0.1nM进行两次重复实验)测试DsiRNA。单独条形表示三次重复中观察到的平均小鼠KRAS水平,同时显示了标准误差。将小鼠KRAS水平针对HPRT和Rpl23水平归一化。
详细说明
本发明涉及含有双链RNA(“dsRNA”)的组合物及其制备方法,所述组合物能够在体内或体外降低KRAS基因的水平和/或表达。dsRNA的一条链含有长度为19至35个核苷酸的核苷酸序列区,该核苷酸序列区可以引导靶KRAS转录物破坏和/或翻译抑制。
定义
除非另外定义,否则本文所述所有科技术语都具有本发明所属领域技术人员通常了解的含义。以下参考文献将向技术人员提供本发明所用许多术语的一般定义:Singleton等,Dictionary of Microbiology and Molecular Biology(第2版,1994);The CambridgeDictionary of Science and Technology(Walker编辑,1988);The Glossary ofGenetics,第5版,R.Rieger等(编辑),Springer Verlag(1991);以及Hale和Marham,TheHarper Collins Dictionary of Biology(1991)。除非另外详细说明,本文中所用的以下术语具有下文所述定义。
本发明的特征是一个或多个可调节(例如,抑制)KRAS表达的DsiRNA分子。本发明的DsiRNA可任选地结合与KRAS错误调控相关疾病或病症的保持或发展(例如,肿瘤形成和/或生长等)有关的其它基因和/或基因产物调节剂来使用。本发明的DsiRNA试剂调节KRASRNA,例如对应于GenBank登录号NM_033360和NM_004985所提到的cDNA序列的那些,这些序列将于下文叙述且在本文中一般称为“KRAS”。
参考示例性的KRAS RNA而提供本发明各个方面和实施方案的以下说明,该示例性的KRAS RNA在本文中一般称为KRAS。然而,这样的参考只是意在示例性的,并且本发明各个方面和实施方案也针对替代性的KRASRNA,例如突变KRAS RNA或其它KRAS剪接变体。某些方面和实施方案还针对KRAS通路中所涉及的其它基因,包括其错误调控与KRAS的错误调控联合而起作用(或者受KRAS调控影响或影响KRAS调控)以产生可作为治疗靶的表型效应(例如,肿瘤形成和/或生长等)的基因。可以使用DsiRNA和本文所述的使用KRAS靶向性DsiRNA的方法靶向这些另外的基因。因此,所述另外的基因的抑制和这种抑制的效应可如本文所述进行。
术语“KRAS”是指编码KRas蛋白质、肽或多肽(例如,KRAS转录物,例如KRASGenbank登录号NM_033360.2和NM_004985.3的序列)的核酸序列。在某些实施方案中,术语“KRAS”也意在包括其它KRAS编码序列,例如其它KRAS同种型、突变KRAS基因、KRAS基因的剪接变体和KRAS基因多态性。术语“Kras”用于指KRAS基因/转录物的多肽基因产物,例如Kras蛋白质、肽或多肽,例如KRAS Genbank登录号NM_033360.2和NM_004985.3所编码者。
本文中使用的“KRAS相关疾病或病症”是指本领域中已知与改变的KRAS表达、水平和/或活性相关的疾病或病症。值得注意的是,“KRAS相关疾病或病症”包括癌症和/或增生性疾病、病况或病症。
如本领域已知,本文中使用的“增生性疾病”或“癌症”是指以不受调控的细胞生长或复制为特征的疾病、病况、特征、基因型或表型;包括白血病,例如急性骨髓性白血病(AML)、慢性骨髓性白血病(CML)、急性淋巴细胞性白血病(ALL)和慢性淋巴细胞性白血病;AIDS相关癌症,例如卡波西氏肉瘤(Kaposi's sarcoma);乳腺癌;骨癌,例如骨肉瘤、软骨肉瘤、尤文氏肉瘤(Ewing's sarcoma)、纤维肉瘤、巨细胞瘤、釉质瘤和脊索瘤;脑瘤,例如脑膜瘤、成胶质细胞瘤、低级别星形细胞瘤、少突胶质细胞瘤、垂体瘤、神经鞘瘤和转移性脑瘤;头颈癌症,包括各种淋巴瘤,例如套细胞淋巴瘤、非霍奇金氏淋巴瘤(non-Hodgkinslymphoma)、腺瘤、鳞状细胞癌、喉癌、胆囊和胆管癌、视网膜癌(例如视网膜母细胞瘤)、食道癌、胃癌、多发性骨髓瘤、卵巢癌、子宫癌、甲状腺癌、睾丸癌、子宫内膜癌、黑色素瘤、结肠直肠癌、肺癌、膀胱癌、前列腺癌、肺癌(包括非小细胞肺癌)、胰腺癌、肉瘤、威尔姆氏肿瘤(Wilms'tumor)、宫颈癌、头颈癌、皮肤癌、鼻咽癌、脂肪肉瘤、上皮肿瘤、肾细胞癌、胆囊腺癌、腮腺腺癌、子宫内膜肉瘤、多重耐药性癌;以及增生性疾病和病况,例如与肿瘤血管生成有关的新血管形成、黄斑变性(例如,湿性/干性AMD)、角膜新血管形成、糖尿病视网膜病变、新血管性青光眼、近视性变性,以及其它增生性疾病和病况,例如再狭窄和多囊性肾病,和可单独或与其它疗法组合响应细胞或组织中疾病相关基因表达调节的其它癌症或者增生性疾病、病况、特征、基因型或表型。
在某些实施方案中,评估DsiRNA介导的KRAS靶序列抑制。在这些实施方案中,通过本领域公认的方法(例如,RT-PCR、RNA印迹(Northern blot)、表达阵列等),任选经由比较在本发明抗KRAS DsiRNA存在下与不存在这一抗KRAS DsiRNA情况下的KRAS水平,来评估KRAS RNA水平。在某些实施方案中,将在抗KRAS DsiRNA存在下的KRAS水平与在单独媒介物存在下、在针对不相关靶RNA的DsiRNA存在下或在不存在任何处理的情况下所观察到的KRAS水平相比较。同样公认的是,可以评估Kras蛋白质的水平以用于指示KRAS RNA水平和/或DsiRNA抑制KRAS表达的程度,因此也可以采用本领域公认的评估KRAS蛋白质水平的方法(例如,蛋白质印迹法(Western blot)、免疫沉淀法、其它基于抗体的方法等)来检查本发明DsiRNA的抑制作用。如果当将本发明的抗KRAS DsiRNA施用于体系(例如,无细胞体外体系)、细胞、组织或生物体时,观察到KRAS RNA或蛋白质水平与适当的对照物相比存在统计显著降低,那么本发明的抗KRAS DsiRNA被认为具有“KRAS抑制活性”。实验值和所进行的重复试验次数的分布将易于决定被认为是统计学显著(如通过本领域中已知的确定统计显著性的标准方法所评估)的KRAS RNA或蛋白质降低水平(以%或以绝对项表示)的参数。然而,在某些实施方案中,“KRAS抑制活性”是根据体系、细胞、组织或生物体中KRAS水平降低的百分数或绝对水平来定义。例如,在某些实施方案中,如果观察到在本发明的DsiRNA存在下KRAS RNA相对于在适合对照物所观察到的KRAS水平存在至少5%降低或至少10%降低,那么认为本发明的DsiRNA具有KRAS抑制活性。(例如,在某些实施方案中,如果观察到KRAS水平相对于对照物存在例如5%或10%降低,那么可认为组织和/或受试者的体内KRAS水平受本发明的DsiRNA试剂抑制。)在某些其它实施方案中,如果观察到KRAS RNA水平相对于适当的对照物降低至少15%、相对于适当的对照物降低至少20%、相对于适当的对照物降低至少25%、相对于适当的对照物降低至少30%、相对于适当的对照物降低至少35%、相对于适当的对照物降低至少40%、相对于适当的对照物降低至少45%、相对于适当的对照物降低至少50%、相对于适当的对照物降低至少55%、相对于适当的对照物降低至少60%、相对于适当的对照物降低至少65%、相对于适当的对照物降低至少70%、相对于适当的对照物降低至少75%、相对于适当的对照物降低至少80%、相对于适当的对照物降低至少85%、相对于适当的对照物降低至少90%、相对于适当的对照物降低至少95%、相对于适当的对照物降低至少96%、相对于适当的对照物降低至少97%、相对于适当的对照物降低至少98%或相对于适当的对照物降低至少99%,那么认为本发明的DsiRNA具有KRAS抑制活性。在一些实施方案中,对于被认为具有KRAS抑制活性的DsiRNA,KRAS的完全抑制是必需的。在某些模型(例如,细胞培养物)中,如果观察到KRAS水平相对于合适的对照物降低至少50%,那么认为DsiRNA具有KRAS抑制活性。在某些其它实施方案中,如果观察到KRAS水平相对于合适的对照物降低至少80%,那么认为DsiRNA具有KRAS抑制活性。
也可以随时间(持续时间)以及随浓度范围(效力)来评估KRAS抑制活性,同时评估具有KRAS抑制活性的DsiRNA的构成,所述KRAS抑制活性根据施用浓度和施用后持续时间来调整。因此,在某些实施方案中,如果施用后在2小时、5小时、10小时、1天、2天、3天、4天、5天、6天、7天、8天、9天、10天或更长的持续时间观察到KRAS活性降低至少50%,那么认为本发明的DsiRNA具有KRAS抑制活性。在其它实施方案中,如果在细胞环境中,在1nM或更低、500pM或更低、200pM或更低、100pM或更低、50pM或更低、20pM或更低、10pM或更低、5pM或更低、2pM或更低或者甚至1pM或更低的浓度下观察到KRAS抑制活性(例如,在某些实施方案中,KRAS的至少50%抑制),那么认为本发明的DsiRNA是有效的KRAS抑制剂。
在某些实施方案中,在提到本发明的抗KRAS DsiRNA时使用了短语“实质上由……组成”。在一些此类实施方案中,“实质上由……组成”是指包含具有至少一定水平的KRAS抑制活性(例如,至少50%KRAS抑制活性)的本发明的DsiRNA,并且也包含一种或多种不显著影响该DsiRNA的KRAS抑制活性的其它组分和/或修饰的组合物。例如,在某些实施方案中,组合物“实质上由本发明的DsiRNA组成”,其中该组合物中本发明DsiRNA的修饰和/或DsiRNA相关组分不会使KRAS抑制活性(任选地包括KRAS抑制活性的效力或持续时间)相对于分离的本发明DsiRNA改变超过3%、超过5%、超过10%、超过15%、超过20%、超过25%、超过30%、超过35%、超过40%、超过45%或超过50%。在某些实施方案中,即使在其它组分或修饰存在下KRAS抑制活性发生较显著的降低(例如,功效、持续时间和/或效力降低80%、降低90%等),而其中在其它组分或修饰存在下KRAS抑制活性未显著升高(例如,观察到的KRAS抑制活性水平小于所观察的本发明分离的DsiRNA的抑制活性水平的10%),那么认为组合物实质上由本发明的DsiRNA组成。
本文中使用的的术语“核酸”是指呈单链或双链形式的脱氧核糖核苷酸、核糖核苷酸或经过修饰的核苷酸和其聚合物。该术语涵盖含有已知核苷酸类似物或经过修饰的骨架残基或键联的核酸,这些核酸是合成的、天然的且非天然的,具有与参考核酸类似的结合性质,而且按照与参考核苷酸类似的方式代谢。这些类似物的实例包括但不限于,硫代磷酸酯、氨基磷酸酯、甲基磷酸酯、手性甲基磷酸酯、2-O-甲基核糖核苷酸、肽-核酸(PNA)。
如本领域中公认的,本文中使用的“核苷酸”用于包括本领域众所周知的天然碱基(标准)和经过修饰的碱基的核苷酸。这些碱基一般位于核苷酸糖部分的1'位。核苷酸一般包含碱基、糖和磷酸基。核苷酸的糖、磷酸和/或碱基部分可以是未修饰的或经过修饰的,(也可互换称为核苷酸类似物、经过修饰的核苷酸、非天然核苷酸、非标准核苷酸等;参见例如Usman和McSwiggen,同上文;Eckstein等,国际PCT公开No.WO92/07065;Usman等,国际PCT公开No.WO93/15187;Uhlman和Peyman,同上文,全部在此以引用的方式并入本文)。本领域中已知若干经过修饰的核酸碱基的实例,如Limbach等,Nucleic Acids Res.22:2183,1994中所概述。可以引入核酸分子中的碱基修饰的一些非限制性实例包括次黄嘌呤、嘌呤、吡啶-4-酮、吡啶-2-酮、苯基、假尿嘧啶、2,4,6-三甲氧基苯、3-甲基尿嘧啶、二氢尿苷、萘基、氨基苯基、5-烷基胞苷(例如,5-甲基胞苷)、5-烷基尿苷(例如,核糖胸腺嘧啶)、5-卤代尿苷(例如,5-溴尿苷)或者6-氮杂嘧啶或6-烷基嘧啶(例如,6-甲基尿苷)、丙炔等(Burgin,等,Biochemistry35:14090,1996;Uhlman和Peyman,同上文)。在这一方面中,“经过修饰的碱基”是指在1'位除腺嘌呤、鸟嘌呤、胞嘧啶和尿嘧啶外的核苷酸碱基或其等效物。
本文中使用的“经过修饰的核苷酸”是指在核苷、核碱基、戊糖环或磷酸基中具有一种或多种修饰的核苷酸。例如,经过修饰的核苷酸不包括含有单磷酸腺苷、单磷酸鸟苷、单磷酸尿苷和单磷酸胞苷的核糖核苷酸,以及含有单磷酸脱氧腺苷、单磷酸脱氧鸟苷、单磷酸脱氧胸苷和单磷酸脱氧胞苷的脱氧核糖核苷酸。修饰包括由修饰核苷酸的酶(例如甲基转移酶)修饰产生的天然修饰。经过修饰的核苷酸还包括合成或非天然的核苷酸。核苷酸中合成或非天然修饰包括具有2'修饰(例如2'-甲氧基乙氧基、2'-氟、2'-烯丙基、2'-O-[2-(甲基氨基)-2-氧代乙基]、4'-硫代、4'-CH2-O-2'-桥、4'-(CH2)2-O-2'-桥、2'-LNA和2'-O-(N-甲基氨基甲酸酯))的修饰或包含碱基类似物的修饰。与本公开所述的2'-修饰的核苷酸相关,“氨基”是指2'-NH2或2'-O-NH2,其可以是经过修饰的或未修饰的。这些经过修饰的基团描述于例如Eckstein等,美国专利No.5,672,695,以及Matulic-Adamic等,美国专利No.6,248,878中。
关于本公开的核酸分子,修饰可根据这些试剂的模式而存在于双链核糖核酸(dsRNA)的一条或两条链上。本文中使用的“交替位置”是指每隔一个核苷酸是经过修饰的核苷酸或在指定长度的链dsRNA上每一经过修饰的核苷酸之间有一个未修饰的核苷酸(例如,未修饰的核糖核苷酸)的模式(例如,5'-MNMNMN-3';3'-MNMNMN-5';其中M是经过修饰的核苷酸,且N是未修饰的核苷酸)。根据位置编号的惯例,修饰模式是从5'或3'末端的第一核苷酸位置开始,例如,如本文所述(在某些实施方案中,1位是在本发明DsiRNA试剂的预计Dicer裂解事件之后根据链的末端残基而指定;因此,1位并不总是构成加工前本发明试剂的3'末端或5'末端残基)。在交替位置处经过修饰的核苷酸的模式可出现在整个链长度上,但在某些实施方案中分别包括含有至少2、3、4、5、6或7个经过修饰的核苷酸的至少4、6、8、10、12、14个核苷酸。本文中使用的“交替位置对”是指在指定长度的链dsRNA上两个连续的经过修饰的核苷酸由两个连续的未修饰的核苷酸分隔开的模式(例如,5'-MMNNMMNNMMNN-3';3'-MMNNMMNNMMNN-5';其中M是经过修饰的核苷酸且N是未修饰的核苷酸)。根据位置编号的惯例,修饰模式是从5'或3'末端的第一核苷酸位置开始,例如本文所述者。在交替位置处经过修饰的核苷酸的模式可出现在整个链长度上,但在某些实施方案中分别优选地包括含有至少4、6、8、10、12或14个经过修饰的核苷酸的至少8、12、16、20、24、28个核苷酸。应强调的是,上述修饰模式是示例性的,且不旨在限制本发明的范围。
本文中使用的“碱基类似物”是指位于可并入核酸双链体中的经过修饰的核苷酸中核苷酸糖部分的1'位(或可并入核酸双链体中的核苷酸糖部分取代物的等效位置)的杂环部分。在本发明dsRNA中,碱基类似物一般为嘌呤或嘧啶碱基,不包括常见碱基:鸟嘌呤(G)、胞嘧啶(C)、腺嘌呤(A)、胸腺嘧啶(T)和尿嘧啶(U)。碱基类似物可与dsRNA中的其它碱基或碱基类似物形成双链体。碱基类似物包括可用于本发明化合物和方法中的碱基类似物,例如,Benner的美国专利No.5,432,272和No.6,001,983以及Manoharan的美国专利公开No.20080213891中所公开的那些,这些专利以引用的方式并入本文。碱基的非限制性实例包括次黄嘌呤(I)、黄嘌呤(X)、3β-D-呋喃核糖基-(2,6-二氨基嘧啶)(K)、3-β-D-呋喃核糖基-(1-甲基-吡唑并[4,3-d]嘧啶-5,7(4H,6H)-二酮)(P)、异胞嘧啶(iso-C)、异鸟嘌呤(iso-G)、1-β-D-呋喃核糖基-(5-硝基吲哚)、1-β-D-呋喃核糖基-(3-硝基吡咯)、5-溴尿嘧啶、2-氨基嘌呤、4-硫代-dT、7-(2-噻吩基)-咪唑并[4,5-b]吡啶(Ds)和吡咯-2-甲醛(Pa)、2-氨基-6-(2-噻吩基)嘌呤(S)、2-氧代吡啶(Y)、二氟甲苯基、4-氟-6-甲基苯并咪唑、4-甲基苯并咪唑、3-甲基羟基异喹啉基、5-甲基羟基异喹啉基和3-甲基-7-丙炔基羟基异喹啉基、7-氮杂吲哚基、6-甲基-7-氮杂吲哚基、咪唑并吡啶基、9-甲基-咪唑并吡啶基、吡咯并吡嗪基、羟基异喹啉基、7-丙炔基羟基异喹啉基、丙炔基-7-氮杂吲哚基、2,4,5-三甲基苯基、4-甲基吲哚基、4,6-二甲基吲哚基、苯基、萘基、蒽基、菲基、芘基、茋基(stilbenzyl)、并四苯基、并五苯基和其结构衍生物(Schweitzer等,J.Org.Chem.,59:7238-7242(1994);Berger等,Nucleic Acids Research,28(15):2911-2914(2000);Moran等,J.Am.Chem.Soc.,119:2056-2057(1997);Morales等,J.Am.Chem.Soc.,121:2323-2324(1999);Guckian等,J.Am.Chem.Soc.,118:8182-8183(1996);Morales等,J.Am.Chem.Soc.,122(6):1001-1007(2000);McMinn等,J.Am.Chem.Soc.,121:11585-11586(1999);Guckian等,J.Org.Chem.,63:9652-9656(1998);Moran等,Proc.Natl.Acad.Sci.,94:10506-10511(1997);Das等,J.Chem.Soc.,Perkin Trans.,1:197-206(2002);Shibata等,J.Chem.Soc.,Perkin Trans.,1:1605-1611(2001);Wu等,J.Am.Chem.Soc.,122(32):7621-7632(2000);O'Neill等,J.Org.Chem.,67:5869-5875(2002);Chaudhuri等,J.Am.Chem.Soc.,117:10434-10442(1995);和美国专利No.6,218,108.)。碱基类似物还可以是通用碱基。
本文中使用的“通用碱基”是指位于经过修饰的核苷酸中核苷酸糖部分的1'位或核苷酸糖部分取代物中等效位置的杂环部分,该杂环部分当存在于核酸双链体中时,可与一种以上碱基相对定位,同时不改变双螺旋结构(例如,磷酸骨架的结构)。此外,通用碱基不会破坏其所驻留的单链核酸与靶核酸形成双链体的能力。含有通用碱基的单链核酸与靶核酸形成双链体的能力可通过本领域技术人员显而易见的方法测定(例如,UV吸光度、圆二色性、凝胶迁移法、单链核酸酶敏感性等)。另外,可以改变能观察到双链体形成的条件,以确定双链体稳定性或形成,例如,温度,如解链温度(Tm),与核酸双链体稳定性相关。相较于与靶核酸精确互补的参考单链核酸,含有通用碱基的单链核酸与靶核酸形成的双链体的Tm低于与互补核酸形成的双链体。然而,与其中通用碱基被碱基置换而产生单一错配的参考单链核酸相比较,含有通用碱基的单链核酸与靶核酸形成的双链体的Tm高于用具有错配碱基的核酸形成的双链体。
一些通用碱基能够通过在通用碱基与所有碱基鸟嘌呤(G)、胞嘧啶(C)、腺嘌呤(A)、胸腺嘧啶(T)和尿嘧啶(U)在碱基配对条件下形成氢键,来实现碱基配对。通用碱基不是只与单一互补碱基形成碱基对的碱基。在双链体中,通用碱基可与双链体相对链上与之相对的G、C、A、T和U中每一者不形成氢键、形成一个氢键或形成一个以上氢键。优选地,通用碱基不与双链体相对链上与之相对的碱基相互作用。在双链体中,与通用碱基之间发生的碱基配对不会改变磷酸骨架的双螺旋结构。通用碱基也可以借助堆叠相互作用与相同核酸链上的相邻核苷酸中的碱基相互作用。这种堆叠相互作用可使双链体稳定,尤其是在通用碱基不与双链体相对链上与之相对定位的碱基形成任何氢键的情形中。通用结合核苷酸的非限制性实例包括肌苷、1-β-D-呋喃核糖基-5-硝基吲哚和/或1-β-D-呋喃核糖基-3-硝基吡咯(Quay等的美国专利申请公开No.20070254362;Van Aerschot等,An acyclic5-nitroindazole nucleoside analogue as ambiguous nucleoside.Nucleic AcidsRes.1995年11月;23(21):4363-70;Loakes等,3-Nitropyrrole and5-nitroindole asuniversal bases in primers for DNA sequencing and PCR.Nucleic Acids Res.1995年7月11日;23(13):2361-6;Loakes和Brown,5-Nitroindole as an universal baseanalogue.Nucleic Acids Res.1994年10月11日;22(20):4039-43)。
本文中使用的“环”是指由核酸的单一链形成的结构,在该结构中,侧接特定单链核苷酸区的互补区按使互补区之间的单链核苷酸区被排除在双链体形成或Watson-Crick碱基配对外的方式杂交。环是任何长度的单链核苷酸区。环的实例包括例如发夹(hairpin)、茎环或延伸环等结构中存在的未配对核苷酸。
在有关dsRNA的上下文中,本文中使用的“延伸环”是指单链环以及侧接该环的另外1、2、3、4、5、6或多达20个碱基对或双链体。在延伸环中,在5'侧侧接该环的核苷酸与在3'侧侧接该环的核苷酸形成双链体。延伸环可形成发夹或茎环。
在有关dsRNA的上下文中,本文中使用的“四核苷酸环”是指由四个核苷酸组成的环(单链区),该环形成稳定的二级结构,有助于使相邻Watson-Crick杂交的核苷酸稳定。在不受理论限制的情况下,四核苷酸环可通过堆叠相互作用使相邻Watson-Crick碱基对稳定。此外,四核苷酸环中四个核苷酸间的相互作用包括但不限于,非Watson-Crick碱基配对、堆叠相互作用、氢键和接触相互作用(Cheong等,Nature1990年8月16日;346(6285):680-2;Heus和Pardi,Science1991年7月12日;253(5016):191-4)。四核苷酸环使相邻双链体的解链温度(Tm)升高,其高于所预期的由四个随机碱基组成的简易模型环序列的Tm。例如,在10mM NaHPO4中,四核苷酸环可使包含长度为至少2个碱基对的双链体的发夹的解链温度为至少55℃。四核苷酸环可以含有核糖核苷酸、脱氧核糖核苷酸、经过修饰的核苷酸和其组合。RNA四核苷酸环的实例包括UNCG家族四核苷酸环(例如,UUCG)、GNRA家族四核苷酸环(例如,GAAA)和CUUG四核苷酸环。(Woese等,Proc Natl Acad Sci U S A.1990年11月;87(21):8467-71;Antao等,Nucleic Acids Res.1991年11月11日;19(21):5901-5)。DNA四核苷酸环的实例包括d(GNNA)家族四核苷酸环(例如,d(GTTA))、d(GNRA)家族四核苷酸环、d(GNAB)家族四核苷酸环、d(CNNG)家族四核苷酸环、d(TNCG)家族四核苷酸环(例如,d(TTCG))。(Nakano等,Biochemistry,41(48),14281-14292,2002.;SHINJI等,NipponKagakkai Koen Yokoshu第78卷;第2期;第731页(2000)。)
本文中使用的术语“siRNA”是指其中每条链都包含RNA、RNA类似物或RNA和DNA的双链核酸。siRNA包含介于19个与23个之间核苷酸,或包含21核苷酸。siRNA通常在每条链的3'端具有2bp突出,以致siRNA中的双链体区包含17-21个核苷酸或19个核苷酸。通常,siRNA的反义链与KRAS基因/RNA的靶序列充分互补。
本发明的抗KRAS DsiRNA的链长度为至少25个核苷酸。因此,抗KRASDsiRNA含有一个寡核苷酸序列,即第一序列,其长度为至少25个核苷酸且不超过35个或多至50个核苷酸。这一RNA序列的长度可介于26与35个、26与34个、26与33个、26与32个、26与31个、26与30个以及26与29个核苷酸之间。这一序列的长度可以是27或28个核苷酸或27个核苷酸。DsiRNA试剂的第二序列可以是在生物条件下(例如在真核细胞细胞质内)与第一序列退火的序列。一般说来,第二寡核苷酸序列中至少有19个碱基对与第一寡核苷酸序列互补,更通常第二寡核苷酸序列中有21或更多个碱基对或者25或更多个碱基对与第一寡核苷酸序列互补。在一个实施方案中,第二序列的长度与第一序列相同,且DsiRNA试剂为平端。在另一实施方案中,DsiRNA试剂末端具有一个或多个突出。
在某些实施方案中,DsiRNA试剂的第一和第二寡核苷酸序列存在于单独的寡核苷酸链上,这些寡核苷酸链可以是且通常是化学合成的。在一些实施方案中,两条链的长度在26与35个核苷酸之间。在其它实施方案中,两条链的长度在25与30个或26与30个核苷酸之间。在一个实施方案中,两条链的长度为27个核苷酸,完全互补并且具有平端。在本发明某些实施方案中,抗KRAS DsiRNA的第一和第二序列存在于单独RNA寡核苷酸(链)上。在一个实施方案中,一条或两条寡核苷酸链能够用作Dicer的底物。在其它实施方案中,存在至少一种修饰,用以促进Dicer按照使双链RNA结构抑制基因表达的功效最大的定向结合于双链RNA结构。在本发明某些实施方案中,抗KRAS DsiRNA试剂包含长度不同的两条寡核苷酸链,其中抗KRAS DsiRNA在第一条链(有义链)的3'末端具有平端且在第二条链(反义链)的3'末端具有3'突出。DsiRNA也可含有一个或多个脱氧核糖核酸(DNA)碱基取代。
含有两个单独寡核苷酸的适合DsiRNA组合物可通过化学连接基团以化学方式在其退火区外部连接。本领域中已知并可使用许多适合的化学连接基团。适合的基团不会阻断Dicer对DsiRNA的活性,并且不会干扰由靶基因转录的RNA的定向破坏。或者,两个单独寡核苷酸可以通过第三寡核苷酸连接,以致在构成DsiRNA组合物的两个寡核苷酸退火后产生发夹结构。发夹结构不会阻断Dicer对DsiRNA的活性,并且不会干扰靶RNA的定向破坏。
本文中使用的具有与靶RNA或cDNA序列(例如,KRAS mRNA)“充分互补”的序列的dsRNA(例如,DsiRNA或siRNA)是指dsRNA具有的序列足以触发由RNAi机构(例如,RISC复合物)或过程引起的靶RNA破坏(在叙述cDNA序列情况下,RNA序列对应于所述的cDNA序列)。可将dsRNA分子设计成使反义链的每一残基都与靶分子中的残基互补。或者,可在该分子内进行取代,以增加所述分子的稳定性和/或增强其加工活性。取代可以在链内进行,或者可以对链末端的残基进行。在某些实施方案中,取代和/或修饰是在DsiRNA试剂内的特定残基处进行。所述取代和/或修饰可以包括例如,当从DsiRNA试剂有义链的3'末端位置开始编号时,在1、2和3位的一个或多个残基处的脱氧修饰;以及在DsiRNA试剂反义链的3'末端残基处引入2'-O-烷基(例如,2'-O-甲基)修饰,其中这样的修饰也在反义链3'部分的突出位置进行和在DsiRNA试剂的加工形成活性siRNA试剂的区域内包括的DsiRNA反义链替代残基处进行。前述修饰都是作为示例提供,并且不旨在以任何方式进行限制。有关优选DsiRNA试剂结构的其它考虑,包括可对本发明抗KRAS DsiRNA试剂进行的修饰和取代的其它说明,可见于下文中。
短语“双链体区”是指两个互补或基本上互补的寡核苷酸中的区域,所述两个互补或基本上互补的寡核苷酸通过Watson-Crick碱基配对或使互补或基本上互补的寡核苷酸链之间形成双链体的其它方式相互间形成碱基对。例如,具有21个核苷酸单位的寡核苷酸链可与另一具有21个核苷酸单位的寡核苷酸碱基配对,而每条链上只有19个碱基互补或基本上互补,以致“双链体区”由19个碱基对组成。其余碱基对可例如作为5'和3'突出存在。此外,在双链体区内,不需要100%互补;在双链体区内允许出现基本上互补。基本上互补是指各链之间的互补性使其能够在生物条件下退火。本领域众所周知凭经验确定两条链是否能够在生物条件下退火的技术。或者,可以合成两条链,并在生物条件下加在一起,以确定其是否相互退火。
单链核酸在多个碱基内碱基配对称为“杂交”。杂交通常在生理或生物相关条件(例如,分子内:pH7.2,140mM钾离子;细胞外:pH7.4,145mM钠离子)下确定。杂交条件一般含有单价阳离子和生物学上可接受的缓冲液,并且可以含有或可不含有二价阳离子、复合阴离子(例如葡糖酸钾中的葡糖酸根)、不带电荷物质(例如蔗糖)和用以降低样品中水的活性的惰性聚合物(例如PEG)。这样的条件包括可形成碱基对的条件。
杂交是通过解离形成双链体的单链核酸所需的温度(即,解链温度;Tm)而度量。杂交条件也是可以形成碱基对的条件。可以使用各种严格度条件来测定杂交(参见例如,Wahl,G.M.和S.L.Berger(1987)Methods Enzymol.152:399;Kimmel,A.R.(1987)MethodsEnzymol.152:507)。严格的温度条件将通常包括至少约30℃,更优选至少约37℃且最优选至少约42℃的温度。预期长度小于50个碱基对的杂交物的杂交温度应比该杂交物的解链温度(Tm)低5-10℃,其中Tm是根据以下等式确定。对于长度小于18个碱基对的杂交物,Tm(℃)=2(A+T碱基的数量)+4(G+C碱基的数量)。对于长度介于18与49个碱基对之间的杂交物,Tm(℃)=81.5+16.6(log10[Na+])+0.41(%G+C)-(600/N),其中N是杂交物中碱基的数目,且[Na+]是杂交缓冲液中钠离子的浓度(对于1×SSC,[Na+]=0.165M)。例如,杂交测定缓冲液示出在表1中。
表1.
杂交条件的有用变化对本领域技术人员将是显而易见的。本领域技术人员熟知杂交技术,并描述于例如以下文献中:例如,Benton和Davis(Science196:180,1977);Grunstein和Hogness(Proc.Natl.Acad.Sci.,USA72:3961,1975);Ausubel等(CurrentProtocols in Molecular Biology,Wiley Interscience,New York,2001);Berger和Kimmel(Antisense to Molecular Cloning Techniques,1987,Academic Press,NewYork);以及Sambrook等,Molecular Cloning:A Laboratory Manual,Cold Spring HarborLaboratory Press,New York。
本文中使用的“寡核苷酸链”是单链核酸分子。寡核苷酸可包含核糖核苷酸、脱氧核糖核苷酸、经过修饰的核苷酸(例如,具有2'修饰的核苷酸、合成碱基类似物等)或其组合。这种经过修饰的寡核苷酸优于天然形式,因为其具有例如增强的细胞吸收且在核酸酶存在下具有增强的稳定性等性质。
本文中使用的术语“核糖核苷酸”涵盖天然和合成、未修饰的和经过修饰的核糖核苷酸。修饰包括寡核苷酸中糖部分、碱基部分和/或核糖核苷酸之间键联的变化。本文中使用的术语“核糖核苷酸”尤其不包括脱氧核糖核苷酸,其在2'核糖环位置具有单一质子基团。
本文中使用的术语“脱氧核糖核苷酸”涵盖天然和合成、未修饰的和经过修饰的脱氧核糖核苷酸。修饰包括寡核苷酸中糖部分、碱基部分和/或脱氧核糖核苷酸之间键联的变化。本文中使用的术语“脱氧核糖核苷酸”还包括不允许dsRNA试剂的Dicer裂解的经过修饰的核糖核苷酸,例如2'-O-甲基核糖核苷酸、硫代磷酸修饰的核糖核苷酸残基等,这些核糖核苷酸都不允许在此类残基的键合处发生Dicer裂解。
本文中使用的术语“PS-NA”是指硫代磷酸修饰的核苷酸残基。因此,术语“PS-NA”涵盖硫代磷酸酯修饰的核糖核苷酸(“PS-RNA”)和硫代磷酸修饰的脱氧核糖核苷酸(“PS-DNA”)。
本文中使用的“Dicer”是指RNase III家族中将dsRNA或含dsRNA分子(例如双链RNA(dsRNA)或微RNA(miRNA)前体)裂解成长度为19-25个核苷酸,通常在3'端具有两个碱基的突出的双链核酸片段的内切核糖核酸酶。对于本发明的dsRNA而言,由本发明试剂的dsRNA区形成的双链体可被Dicer识别,并且在双链体至少一条链上是Dicer底物。Dicer催化RNA干扰通路中的第一步,随后引起靶RNA降解。人Dicer的蛋白质序列提供于NCBI数据库中,登录号为NP_085124,以引用的方式并入本文。
Dicer“裂解”按如下测定(例如,参见Collingwood等,Oligonucleotides18:187–200(2008))。在Dicer裂解测定中,37℃下,在存在或不存在1单位重组人Dicer(Stratagene,La Jolla,CA)的20μL20mM Tris pH8.0、200mM NaCl、2.5mM MgCl2中孵育RNA双链体(100pmol)18到24小时。使用Performa SR96孔板(Edge Biosystems,Gaithersburg,MD)使样品脱盐。使用由ThermoFinnigan TSQ7000、Xcalibur数据系统、ProMass数据处理软件和Paradigm MS4HPLC(Michrom BioResources,Auburn,CA)组成的Oligo HTCS系统(Novatia,Princeton,NJ;Hail等,2004),在用Dicer处理前和处理后对双链体RNA进行电喷雾电离液相色谱质谱分析(ESI-LCMS)。在本测定中发生Dicer裂解,其中至少5%、10%、20%、30%、40%、50%、60%、70%、80%、90%、95%或甚至100%的Dicer底物dsRNA(即,25-30bp dsRNA,优选26-30bp dsRNA)被裂解成较短dsRNA(例如19-23bp dsRNA,优选21-23bp dsRNA)。
本文中使用的“Dicer裂解位点”是指Dicer裂解dsRNA(例如,本发明DsiRNA试剂的dsRNA区)的位点。Dicer含有两个RNase III域,其通常裂解dsRNA的有义链和反义链。RNaseIII域与PAZ域之间的平均距离决定其所产生的短双链核酸片段的长度,并且这一距离可变化(Macrae I等(2006)."Structural basis for double-stranded RNA processing byDicer".Science311(5758):195–8.)。如图1和图4中所示,预计Dicer裂解本发明的某些双链核糖核酸,这些双链核糖核酸具有的反义链为在远离反义链的3'末端的第21位与第22位核苷酸之间的位点以及在远离有义链5'末端的第21位与第22位核苷酸之间的相应位点具有2个核苷酸的3'突出。与图1和图4所描述的dsRNA分子不同的dsRNA分子的预计和/或主要Dicer裂解位点可通过本领域公认的方法(包括Macrae等所述的方法)以类似方式鉴定。虽然图1和图4中所描述的Dicer裂解事件产生21个核苷酸的siRNA,但应注意,dsRNA(例如DsiRNA)的Dicer裂解可导致产生长度为19至23个核苷酸的经过Dicer加工的siRNA长度。实际上,在某些实施方案中,双链DNA区可包括在dsRNA内,以达到引导Dicer主要切除通常非优选的19mer或20mer siRNA而非21mer的目的。
在dsRNA的5'末端或3'末端具有一个或多个游离端的双链体的情况下,本文中使用的“突出”是指未配对的核苷酸。在某些实施方案中,突出是在反义链或有义链上的3'或5'突出。在一些实施方案中,突出是长度介于1个与6个核苷酸之间,任选1至5个、1至4个、1至3个、1至2个、2至6个、2至5个、2至4个、2至3个、3至6个、3至5个、3至4个、4至6个、4至5个、5至6个核苷酸,或1、2、3、4、5或6个核苷酸的3'突出。
本文中使用的术语“RNA加工”是指由siRNA、miRNA或RNase H通路的组分(例如,Drosha、Dicer、Argonaute2或其它RISC内切核糖核酸酶和RNaseH)所进行的加工活动,下文将更为详细地描述(参见下文的“RNA加工”一节)。本术语明显不同于RNA5'加帽的转录后加工以及经由非RISC介导的过程或非RNase H介导的过程的RNA降解。所述RNA的“降解”可采用数种形式,例如脱腺苷化(除去3'多聚腺苷酸尾)和/或借助数种内切核酸酶或外切核酸酶(例如RNase III、RNase P、RNase T1、RNase A(1、2、3、4/5)、寡核苷酸酶等)中的一种或多种进行的部分或全部RNA主体的核酸酶消化。
所谓“同源序列”是指一个或多个多核苷酸序列(例如基因、基因转录物和/或非编码多核苷酸)共有的核苷酸序列。例如,同源序列可以是两个或更多个编码相关但不同的蛋白质的基因共有的核苷酸序列,例如某一基因家族的不同成员、不同蛋白质表位、不同蛋白质同种型或完全不同的基因,例如细胞因子和其相应受体。同源序列可以是两个或更多个非编码多核苷酸,例如非编码DNA或RNA、调控序列、内含子和转录控制或调控位点共有的核苷酸序列。同源序列还可以包括一个以上多核苷酸序列共有的保守序列区。同源性无需为完全同源(例如,100%),部分同源的序列也涵盖于本发明中(例如,99%、98%、97%、96%、95%、94%、93%、92%、91%、90%、89%、88%、87%、86%、85%、84%、83%、82%、81%、80%等)。事实上,本发明DsiRNA试剂的设计和使用涵盖使用这种DsiRNA试剂的可能性,该DsiRNA试剂不仅针对KRAS中与当前所述DsiRNA试剂完全互补的的靶RNA,而且还针对序列与所述DsiRNA试剂例如仅99%、98%、97%、96%、95%、94%、93%、92%、91%、90%、89%、88%、87%、86%、85%、84%、83%、82%、81%、80%等互补的靶KRAS RNA。类似地,预期技术人员可容易地改变当前所述的本发明DsiRNA试剂,以增强所述DsiRNA试剂与靶KRAS RNA(例如KRAS特定等位基因变体(例如,增强治疗影响的等位基因))之间的互补程度。事实上,相对于靶KRAS序列具有插入、缺失和单点突变的DsiRNA试剂序列对抑制也是有效的。或者,具有核苷酸类似物取代或插入的DsiRNA试剂序列对抑制是有效的。
序列同一性可以通过本领域中已知的序列比较和比对算法测定。为了测定两个核酸序列(或两个氨基酸序列)的同一性百分比,出于最佳比较的目的,将序列进行比对(例如,为实现最佳比对,可在第一序列或第二序列中引入空位)。随后比较相应核苷酸(或氨基酸)位置的核苷酸(或氨基酸残基)。当占据第一序列某一位置的残基与第二序列相应位置的残基相同时,则分子在该位置相同。两个序列之间的同一性百分比是这两个序列共有相同位置的数量的函数(即,同一性%=相同位置的数量/位置总数×100),任选对引入的空位数量和/或引入的空位长度进行罚分。
序列比较和两个序列之间同一性百分比的测定可以使用数学算法完成。在一个实施方案中,比对是在所比对序列具有足够同一性的某一部分上发生,而不是在具有低同一性程度的部分上发生(即,局部比对)。用于比较序列的局部比对算法的优选的非限制性实例是如Karlin和Altschul(1990)Proc.Natl.Acad.Sci.USA87:2264-68的算法,如Karlin和Altschul(1993)Proc.Natl.Acad.Sci.USA90:5873-77中修改的算法。此类算法被并入Altschul等(1990)J.Mol.Biol.215:403-10的BLAST程序(2.0版)中。
在另一个实施方案中,通过引入适当适合空位而对比对进行优化,并测定比对序列长度上的同一性百分比(即,空位比对)。为获得空位比对以达到比较的目的,可以利用如Altschul等,(1997)Nucleic Acid Res.25(17):3389-3402中所述的Gapped BLAST。在另一个实施方案中,通过引入适当的空位而对比对进行优化,并测定比对序列的整个长度上的同一性百分比(即,整体比对)。用于序列的整体比较的数学算法的优选的非限制性实例为Myers和Miller,CABIOS(1989)的算法。这一算法被并入ALIGN程序(2.0版)中,该程序是GCG序列算法软件包的一部分。当利用ALIGN程序来比较氨基酸序列时,可以使用PAM120权重残基表、空位长度罚分12和空位罚分4。
优选DsiRNA反义链与KRAS RNA序列部分之间具有超过80%序列同一性,例如具有80%、81%、82%、83%、84%、85%、86%、87%、88%、89%、90%、91%、92%、93%、94%、95%、96%、97%、98%、99%或甚至100%序列同一性。作为另外的选择,DsiRNA可在功能上定义为能够与KRAS RNA的一部分杂交的核苷酸序列(或寡核苷酸序列)(例如,400mM NaCl、40mMPIPES pH6.4、1mMEDTA、50℃或70℃杂交,12-16小时;随后洗涤)。其它优选的杂交条件包括70℃下在1×SSC或50℃下在1×SSC、50%甲酰胺中杂交,随后70℃下在0.3×SSC中洗涤;或70℃下在4×SSC或50℃下在4×SSC、50%甲酰胺中杂交,随后在67℃下于1×SSC中洗涤。预期长度小于50个碱基对的杂交物的杂交温度应比该杂交物的解链温度(Tm)低5-10℃,其中Tm是根据以下等式确定。对于长度小于18个碱基对的杂交物,Tm(℃)=2(A+T碱基的数量)+4(G+C碱基的数量)。对于长度介于18与49个碱基对之间的杂交物,Tm(℃)=81.5+16.6(log10[Na+])+0.41(%G+C)-(600/N),其中N是杂交物中碱基的数目,且[Na+]是杂交缓冲液中钠离子的浓度(对于1×SSC,[Na+]=0.165M)。对于多核苷酸杂交的严格度条件的其它实例提供于Sambrook,J.,E.F.Fritsch和T.Maniatis,1989,Molecular Cloning:A Laboratory Manual,ColdSpring Harbor Laboratory Press,Cold Spring Harbor,N.Y.,第9和第11章,以及Current Protocols in Molecular Biology,1995,F.M.Ausubel等编辑,John Wiley &Sons,Inc.,第2.10和第6.3-6.4节中。相同核苷酸序列的长度可为至少10、12、15、17、20、22、25、27或30个碱基。
所谓“保守序列区”是指多核苷酸中一个或多个区的核苷酸序列在后代之间或从一个生物体系、受试者或生物体到另一个生物体系、受试者或生物体不发生显著变化。多核苷酸可包括编码和非编码DNA和RNA。
所谓“有义区”是指DsiRNA分子中与DsiRNA分子的反义区具有互补性的核苷酸序列。此外,DsiRNA分子的有义区可包含与靶核酸序列具有同源性的核酸序列。
所谓“反义区”是指DsiRNA分子中与靶核酸序列具有互补性的核苷酸序列。此外,DsiRNA分子的反义区包含与DsiRNA分子的有义区具有互补性的核酸序列。
本文中使用的“反义链”是指具有与靶RNA序列互补的序列的单链核酸分子。当反义链含有具有碱基类似物的经过修饰的核苷酸时,该反义链在其整个长度上未必互补,但必须至少与靶RNA杂交。
本文中使用的“有义链”是指具有与反义链序列互补的序列的单链核酸分子。当反义链含有具有碱基类似物的经过修饰的核苷酸时,有义链无需在反义链的整个长度上互补,但必须至少与反义链形成双链体。
本文中使用的“引导链”是指dsRNA或含dsRNA分子的单链核酸分子,其序列与靶RNA序列充分互补,由此引起RNA干扰。在由Dicer裂解该dsRNA或含dsRNA分子后,引导链的片段保持与RISC相关联,结合作为RISC复合物的组分的靶RNA,并促进RISC裂解靶RNA。本文中使用的引导链未必指连续的单链核酸,并且可以包含不连续性,优选在Dicer裂解的位点具有不连续性。引导链是反义链。
本文中使用的“过客链(passenger strand)”是指dsRNA或含dsRNA分子的寡核苷酸链,其序列与引导链的序列互补。本文中使用的过客链未必指连续的单链核酸,并且可以包含不连续性,优选在Dicer裂解的位点具有不连续性。过客链是有义链。
“靶核酸”是指表达、水平或活性需加以调节的核酸序列。靶核苷酸可以是DNA或RNA。对于靶向KRAS的试剂,在某些实施方案中,靶核酸是KRASRNA。KRAS RNA靶位点也可以与相应的cDNA序列互换引用。也可以通过靶向KRAS的上游效应子来靶向KRAS水平,或者还可以通过靶向Ras信号传导通路中KRAS下游的分子来调节经过调节或错误调节的KRAS的作用。
所谓“互补”是指,核酸可通过传统的Watson-Crick或其它非传统类型与另一核酸序列形成氢键。就本发明核酸分子来说,核酸分子与其互补序列的结合自由能足以使核酸能够履行相关功能,例如RNAi活性。对核酸分子的结合自由能的测定是本领域熟知的(参见例如,Turner等,1987,CSH Symp.Quant.Biol.LII,第123-133页;Frier等,1986,Proc.Nat.Acad.Sci.USA83:9373-9377;Turner等,1987,J.Am.Chem.Soc.109:3783-3785)。互补性百分比指示某一核酸分子中可与另一核酸序列形成氢键(例如,Watson-Crick碱基配对)的连续残基的百分数(例如,第一寡核苷酸的总共10个核苷酸中有5、6、7、8、9或10个核苷酸与具有10个核苷酸的第二核酸序列碱基配对分别表示50%、60%、70%、80%、90%和100%互补)。“完全互补”是指某一核酸序列的所有连续残基将与另一核酸序列中相同数量的连续残基形成氢键。在一个实施方案中,本发明的DsiRNA分子包含19至30个(例如,19、20、21、22、23、24、25、26、27、28、29或30或更多个)与一个或多个靶核酸分子或其一部分互补的核苷酸。
在一个实施方案中,使用下调或降低KRAS基因表达的本发明DsiRNA分子来治疗、预防或减轻受试者或生物体的KRAS相关性疾病或病症(例如,癌症)。
在本发明一个实施方案中,本发明DsiRNA分子的每一个序列的长度独立地为25至35个核苷酸,在具体实施方案中长度为25、26、27、28、29、30、31、32、33、34或35个核苷酸。在另一实施方案中,本发明的DsiRNA双链体独立地包含25至30个碱基对(例如,25、26、27、28、29或30个)。在另一实施方案中,本发明DsiRNA分子的一条或多条链独立地包含19至35个与靶(KRAS)核酸分子互补的核苷酸(例如,19、20、21、22、23、24、25、26、27、28、29、30、31、32、33、34或35个)。在某些实施方案中,本发明DsiRNA分子具有的双链核苷酸长度介于25与34个核苷酸之间(例如,长度为25、26、27、28、29、30、31、32、33或34个核苷酸;任选地,所有这些核苷酸都与相对链的同源核苷酸碱基配对)。(本发明示例性的DsiRNA分子示出在图1和图4以及下文中。
本文中使用的“细胞”的含义是其通常的生物含义,而且并不指完整的多细胞生物体,例如,具体说来不是指人。细胞可存在于生物体中,例如鸟类、植物和哺乳动物,例如人、牛、羊、猿、猴、猪、狗和猫。细胞可以是原核的(例如,细菌细胞)或真核的(例如,哺乳动物或植物细胞)。细胞可以是体细胞系或生殖系来源、全能或多能、分裂或非分裂的。细胞还可以来源于或者可以包含配子或胚胎、干细胞或完全分化的细胞。在某些方面内,术语“细胞”特指含有一个或多个本公开的分离的dsRNA分子的哺乳动物细胞,例如人细胞。在特定方面,细胞加工dsRNA或含dsRNA分子,引起靶核酸的RNA干扰,并且含有RNAi所需的蛋白质和蛋白质复合物,例如Dicer和RISC。
本发明的DsiRNA分子可直接加入靶细胞或组织,或可以与阳离子脂质形成复合物,包装在脂质体内或以其它方式递送到靶细胞或组织。核酸或核酸复合物可离体或者在体内通过直接皮肤应用、透皮应用或注射而局部施用于相关组织,在此过程中,其可以并入或不并入生物聚合物中。在具体的实施方案中,本发明的核酸分子包含图1和图4以及以下示例性结构中所示出的序列。这些核酸分子的实例实质上由这些图和示例性结构中确定的序列组成。此外,在根据下文DsiRNA试剂的修饰模式的说明来修饰这些试剂的情况中,可以将图1和图4以及以下示例性结构中所述的以化学修饰形式的构建体用于对于图1和图4以及以下示例性结构所述的DsiRNA试剂的所有用途中。
在另一方面,本发明提供含有一个或多个本发明DsiRNA分子的哺乳动物细胞。可将所述一个或多个DsiRNA分子独立地靶向相同或不同位点。
所谓“RNA”是指包含至少一个核糖核苷酸残基的分子。所谓“核糖核苷酸”是指β-D-呋喃核糖部分的2'位具有羟基的核苷酸。这些术语包括双链RNA、单链RNA、分离的RNA,例如部分纯化的RNA、基本上纯的RNA、合成RNA、重组产生的RNA,以及因一个或多个核苷酸的添加、缺失、取代和/或改变而不同于天然RNA的改变的RNA。这些改变可包括例如向DsiRNA末端或内部,例如在RNA的一个或多个核苷酸处加入非核苷酸物质。本发明RNA分子中的核苷酸也可包括非标准核苷酸,例如非天然核苷酸或以化学合成的核苷酸或脱氧核苷酸。这些改变的RNA可称为类似物或天然RNA的类似物。
所谓“受试者”是指作为外植细胞的供体或受体的生物体或者细胞本身。“受试者”还指可以对其施用本发明的DsiRNA试剂的生物体。受试者可以是哺乳动物或哺乳动物细胞,包括人或人细胞。
短语“药学上可接受的载体”是指用于施用治疗剂的载体。示例性载体包括生理盐水、缓冲生理盐水、葡萄糖、水、丙三醇、乙醇和其组合。对于口服施用的药物,药学上可接受的载体包括但不限于,药学上可接受的赋形剂,例如惰性稀释剂、崩解剂、粘合剂、润滑剂、甜味剂、调味剂、着色剂和防腐剂。适合的惰性稀释剂包括碳酸钠和碳酸钙、磷酸钠和磷酸钙以及乳糖,而玉米淀粉和海藻酸是适合的崩解剂。粘合剂可包括淀粉和明胶,而润滑剂(如果存在的话)一般为硬脂酸镁、硬脂酸或滑石。必要时,片剂可涂有例如单硬脂酸甘油酯或二硬脂酸甘油酯等材料,以延缓胃肠道吸收。公开的dsRNA组合物的药学上可接受的载体可以是微胞结构,例如脂质体、衣壳、病毒壳粒、聚合纳米胶囊或聚合微胶囊。
聚合纳米胶囊或微胶囊有助于将封装或结合的dsRNA运输和释放到细胞中。其包括聚合和单体材料,尤其包括聚氰基丙烯酸丁酯。已经公开材料和制造方法的概述(参见Kreuter,1991)。在聚合反应/纳米粒子产生步骤中由单体和/或寡聚前体形成的聚合材料本身是在现有技术中已知的,聚合材料的分子量和分子量分布也是如此,其可以由纳米粒子制造领域的技术人员根据常用技术适当地选择。
本发明的各种方法包括涉及与“适合的对照物”(本文中可互换称为“适当的对照物”)比较值、水平、特征、特性、性质等的步骤。“适合的对照物”或“适当的对照物”是本领域一般技术人员熟悉的可用于比较目的的对照物或标准品。在一个实施方案中,“适合的对照物”或“适当的对照物”是在如本文所述进行RNAi方法前测定的值、水平、特征、特性、性质等。例如,可以在将本发明的RNA沉默试剂(silencing agent)(例如DsiRNA)引入细胞或生物体中之前,测定转录速率、mRNA水平、翻译速率、蛋白质水平、生物活性、细胞特性或性质、基因型、表型等。在另一实施方案中,“适合的对照物”或“适当的对照物”是在表现例如正常特征的细胞或生物体(例如,对照或正常细胞或生物体)中测定的值、水平、特征、特性、性质等。在另一实施方案中,“适合的对照物”或“适当的对照物”是预先确定的值、水平、特征、特性、性质等。
术语“体外”具有其本领域公认的含义,例如涉及纯化的试剂或提取物,例如细胞提取物。术语“体内”也具有其本领域公认的含义,例如涉及生物体中的活细胞,例如永生化细胞、原代细胞、细胞系和/或细胞。
本文中使用的“治疗(treatment)”或“治疗(treating)”定义为对患者应用或施用治疗剂(例如,DsiRNA试剂或载体,或者编码DsiRNA试剂或载体的转基因),或将治疗剂应用或施用于来自患有某一病症的患者的分离的组织或细胞系,以达到治疗、治愈、减轻、缓解、改变、补救、改善、改进或影响该疾病或病症,或者该疾病或病症的症状的目的。术语“治疗(treatment)”或“治疗(treating)”在本文中还用于预防地施用试剂的情形。术语“有效剂量(effective dose)”或“有效剂量(effective dosage)”定义为足以达到或至少部分达到期望效果的量。术语“治疗有效剂量”定义为足以治疗或至少部分停滞已患有某一疾病的患者的疾病和其并发症的量。术语“患者”包括接受预防性或治疗性治疗的人和其它哺乳动物受试者。
抗KRAS DsiRNA试剂的结构
在某些实施方案中,本发明的抗KRAS DsiRNA试剂可具有以下结构:
在一个此类实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基且“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体。在相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中"X"=RNA,"p"=磷酸基,"Y"是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且“D”=DNA。在一个实施方案中,上链是有义链,且下链是反义链。或者,下链是有义链且上链是反义链。
在另一实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且带下划线的残基是2'-O-甲基RNA单体。在相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXP-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且带下划线的残基是2'-O-甲基RNA单体,且“D”=DNA。上链是有义链,且下链是反义链。
在另一此类实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXP-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且带下划线的残基是2'-O-甲基RNA单体。在相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,带下划线的残基是2'-O-甲基RNA单体,且“D”=DNA。上链是有义链,且下链是反义链。
在另一此类实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且带下划线的残基是2'-O-甲基RNA单体。在相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,带下划线的残基是2'-O-甲基RNA单体,且“D”=DNA。上链是有义链,且下链是反义链。
在其它实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且带下划线的残基是2'-O-甲基RNA单体。在相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,带下划线的残基是2'-O-甲基RNA单体,且"D"=DNA。上链是有义链,且下链是反义链。在一个相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基且“X”=2'-O-甲基RNA。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,且“D”=DNA。上链是有义链,且下链是反义链。
在其它实施方案中,DsiRNA包含
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且带下划线的残基是2'-O-甲基RNA单体。在相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,带下划线的残基是2'-O-甲基RNA单体,且"D"=DNA。上链是有义链,且下链是反义链。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基且“X”=2'-O-甲基RNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,且“D”=DNA。上链是有义链,且下链是反义链。
在另一实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且带下划线的残基是2'-O-甲基RNA单体。上链是有义链,且下链是反义链。在相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,带下划线的残基是2'-O-甲基RNA单体,且"D"=DNA。上链是有义链,且下链是反义链。在一个相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基且“X”=2'-O-甲基RNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,且“D”=DNA。上链是有义链,且下链是反义链。
在其它实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且带下划线的残基是2'-O-甲基RNA单体。上链是有义链,且下链是反义链。在相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,带下划线的残基是2'-O-甲基RNA单体,且"D"=DNA。上链是有义链,且下链是反义链。在一个相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基且“X”=2'-O-甲基RNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,且“D”=DNA。上链是有义链,且下链是反义链。
在其它实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且带下划线的残基是2'-O-甲基RNA单体。上链是有义链,且下链是反义链。在相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,带下划线的残基是2'-O-甲基RNA单体,且"D"=DNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基且“X”=2'-O-甲基RNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,且“D”=DNA。上链是有义链,且下链是反义链。
在其它实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且带下划线的残基是2'-O-甲基RNA单体。上链是有义链,且下链是反义链。在一个相关实施方案中,DsiRNA包含:5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,带下划线的残基是2'-O-甲基RNA单体,且"D"=DNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基且“X”=2'-O-甲基RNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,且“D”=DNA。上链是有义链,且下链是反义链。
在其它实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且带下划线的残基是2'-O-甲基RNA单体。上链是有义链,且下链是反义链。在相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,带下划线的残基是2'-O-甲基RNA单体,且"D"=DNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基且“X”=2'-O-甲基RNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,且“D”=DNA。上链是有义链,且下链是反义链。
在其它实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且带下划线的残基是2'-O-甲基RNA单体。上链是有义链,且下链是反义链。在相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,带下划线的残基是2'-O-甲基RNA单体,且"D"=DNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基且“X”=2'-O-甲基RNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,且“D”=DNA。上链是有义链,且下链是反义链。
在其它实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且带下划线的残基是2'-O-甲基RNA单体。上链是有义链,且下链是反义链。在一个相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,带下划线的残基是2'-O-甲基RNA单体,且"D"=DNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基且“X”=2'-O-甲基RNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,且“D”=DNA。上链是有义链,且下链是反义链。
在其它实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且带下划线的残基是2'-O-甲基RNA单体。上链是有义链,且下链是反义链。在相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,带下划线的残基是2'-O-甲基RNA单体,且"D"=DNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基且“X”=2'-O-甲基RNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,且“D”=DNA。上链是有义链,且下链是反义链。
在其它实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且带下划线的残基是2'-O-甲基RNA单体。上链是有义链,且下链是反义链。在一个相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,带下划线的残基是2'-O-甲基RNA单体,且"D"=DNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基且“X”=2'-O-甲基RNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,且“D”=DNA。上链是有义链,且下链是反义链。
在其它实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且带下划线的残基是2'-O-甲基RNA单体。上链是有义链,且下链是反义链。在一个相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,带下划线的残基是2'-O-甲基RNA单体,且"D"=DNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基且“X”=2'-O-甲基RNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,且“D”=DNA。上链是有义链,且下链是反义链。
在其它实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且带下划线的残基是2'-O-甲基RNA单体。上链是有义链,且下链是反义链。在一个相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,带下划线的残基是2'-O-甲基RNA单体,且"D"=DNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基且“X”=2'-O-甲基RNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,且“D”=DNA。上链是有义链,且下链是反义链。
在其它实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且带下划线的残基是2'-O-甲基RNA单体。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,带下划线的残基是2'-O-甲基RNA单体,且"D"=DNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基且“X”=2'-O-甲基RNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,且“D”=DNA。上链是有义链,且下链是反义链。
在其它实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且带下划线的残基是2'-O-甲基RNA单体。上链是有义链,且下链是反义链。在一个相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,带下划线的残基是2'-O-甲基RNA单体,且"D"=DNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基且“X”=2'-O-甲基RNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,且“D”=DNA。上链是有义链,且下链是反义链。
在其它实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且带下划线的残基是2'-O-甲基RNA单体。上链是有义链,且下链是反义链。在一个相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,带下划线的残基是2'-O-甲基RNA单体,且"D"=DNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基且“X”=2'-O-甲基RNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,且“D”=DNA。上链是有义链,且下链是反义链。
在其它实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且带下划线的残基是2'-O-甲基RNA单体。上链是有义链,且下链是反义链。在相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-2′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,带下划线的残基是2'-O-甲基RNA单体,且"D"=DNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基且“X”=2'-O-甲基RNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,且“D”=DNA。上链是有义链,且下链是反义链。
在其它实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且带下划线的残基是2'-O-甲基RNA单体。上链是有义链,且下链是反义链。在一个相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,带下划线的残基是2'-O-甲基RNA单体,且"D"=DNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基且“X”=2'-O-甲基RNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,且“D”=DNA。上链是有义链,且下链是反义链。
在其它实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且带下划线的残基是2'-O-甲基RNA单体。上链是有义链,且下链是反义链。在一个相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,带下划线的残基是2'-O-甲基RNA单体,且"D"=DNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基且“X”=2'-O-甲基RNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-2'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,且“D”=DNA。上链是有义链,且下链是反义链。
在其它实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且带下划线的残基是2'-O-甲基RNA单体。上链是有义链,且下链是反义链。在一个相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,带下划线的残基是2'-O-甲基RNA单体,且"D"=DNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基且“X”=2'-O-甲基RNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,且“D”=DNA。上链是有义链,且下链是反义链。
在其它实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且带下划线的残基是2'-O-甲基RNA单体。上链是有义链,且下链是反义链。在一个相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,带下划线的残基是2'-O-甲基RNA单体,且"D"=DNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXXX-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“p”=磷酸基且“X”=2'-O-甲基RNA。上链是有义链,且下链是反义链。在另一相关实施方案中,DsiRNA包含:
5′-pXXXXXXXXXXXXXXXXXXXXXXXDD-3′
3′-XXXXXXXXXXXXXXXXXXXXXXXXXXXp-5'
其中“X”=RNA,“p”=磷酸基,“X”=2'-O-甲基RNA,且“D”=DNA。上链是有义链,且下链是反义链。
上述修饰模式也可以例如并入下文所述延伸的DsiRNA结构以及错配和/或断裂的DsiRNA结构中。
在另一实施方案中,DsiRNA包含具有相同长度的链,这些链具有1-3个用以使Dicer裂解定向的错配残基(具体说来,当第一条链与第二条链相互退火时,DsiRNA第一条链上的1位、2位或3位(当从3'末端残基编号时)中的一者或多者与第二条链上5'末端区域的相应残基错配)。具有两个末端错配残基的示例性27mer DsiRNA试剂如下所示:
其中“X”=RNA,“p”=磷酸基,“M”=当链退火时不与另一互补链的相应“M”残基碱基配对(形成氢键)的核酸残基(RNA、DNA或非天然或经过修饰的核酸)。此类试剂的任何残基可任选为2'-O-甲基RNA单体–如以上不对称试剂所示,从下(第二)链的3'-末端残基开始,2'-O-甲基RNA单体的交替定位也可用于上述“平端/断裂”DsiRNA试剂中。在一个实施方案中,上链是有义链,且下链是反义链。或者,下链是有义链,且上链是反义链。
在某些其它实施方案中,本发明提供用于RNA干扰(RNAi)的组合物,所述组合物在双链核糖核酸(dsRNA)的区域内具有一个或多个碱基配对的脱氧核糖核苷酸,该区域位于预计的有义链Dicer裂解位点的3'端以及预计的反义链Dicer裂解位点的相应5'端。本发明组合物包含作为前体分子的dsRNA,即,本发明的dsRNA在体内经过加工以产生活性小干扰核酸(siRNA)。dsRNA被Dicer加工成并入RISC中的活性siRNA。
在某些实施方案中,本发明的DsiRNA试剂可具有以下示例性结构(应注意,以下任一示例性结构可例如与具有上述结构的下链修饰模式组合,即,在一个特定实例中,上述任一结构中所示的下链修饰模式被应用于具有以下任一结构的下链的最多27个3'残基;在另一特定实例中,上述任一结构中所示有关下链最多23个3'残基的下链修饰模式被应用于具有以下任一结构的下链的最多23个3'残基):
在一个此类实施方案中,DsiRNA包含下列(示例性“右侧延伸”、“DNA延伸”的DsiRNA):
5′-XXXXXXXXXXXXXXXXXXXXXXXXN*DNDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXN*DNXX-5'
其中“X”=RNA,“Y”是包含0-10个任选为2'-O-甲基RNA单体的RNA单体的任选存在的突出域–在某些实施方案中,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,“D”=DNA,且“N”=1至50或更多,但任选为1-8或1-10。“N*”=0至15或更多,但任选为0、1、2、3、4、5或6。在一个实施方案中,上链是有义链,且下链是反义链。或者,下链是有义链,且上链是反义链。
在相关实施方案中,DsiRNA包含:
3′-YXXXXXXXXXXXXXXXXXXXXXXXXN*DNDD-5'
其中“X”=RNA,“Y”是包含0-10个任选为2'-O-甲基RNA单体的RNA单体的任选存在的突出域–在某些实施方案中,”Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,"D"=DNA,且“N”=1至50或更多,但任选为1-8或1-10。“N*”=0至15或更多,但任选为0、1、2、3、4、5或6。在一个实施方案中,上链是有义链,且下链是反义链。或者,下链是有义链,且上链是反义链。
在另一实施方案中,DsiRNA包含:
5′-XXXXXXXXXXXXXXXXXXXXXXXXN*DNDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXD*DNZZ-5′
其中“X”=RNA,“X”=2'-O-甲基RNA,“Y”是包含0-10个任选为2'-O-甲基RNA单体的RNA单体的任选存在的突出域–在某些实施方案中,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,“D”=DNA,“Z”=DNA或RNA,且“N”=1至50或更多,但任选为1-8或1-10。“N*”=0至15或更多,但任选为0、1、2、3、4、5或6。在一个实施方案中,上链是有义链,且下链是反义链。或者,下链是有义链,且上链是反义链,其中2'-O-甲基RNA单体位于沿上链而不是以上示意图中当前描绘的下链的交替残基上。
在另一此类实施方案中,DsiRNA包含:
5′-XXXXXXXXXXXXXXXXXXXXXXXXN*DNDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXN*DNZZ-5’
其中“X”=RNA,“X”=2'-O-甲基RNA,“Y”是包含0-10个任选为2'-O-甲基RNA单体的RNA单体的任选存在的突出域–在某些实施方案中,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,“D”=DNA,“Z”=DNA或RNA,且“N”=1至50或更多,但任选为1-8或1-10。“N*”=0至15或更多,但任选为0、1、2、3、4、5或6。在一个实施方案中,上链是有义链,且下链是反义链。或者,下链是有义链,且上链是反义链,其中2'-O-甲基RNA单体位于沿上链而不是以上示意图中当前描绘的下链的交替残基上。
在另一此类实施方案中,DsiRNA包含:
5′-XXXXXXXXXXXXXXXXXXXXXXXXN*DNDD-3′
其中“X”=RNA,“X”=2'-O-甲基RNA,“Y”是包含0-10个任选为2'-O-甲基RNA单体的RNA单体的任选存在的突出域–在某些实施方案中,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,“D”=DNA,“Z”=DNA或RNA,且“N”=1至50或更多,但任选为1-8或1-10。“N*”=0至15或更多,但任选为0、1、2、3、4、5或6。在一个实施方案中,上链是有义链,且下链是反义链。或者,下链是有义链,且上链是反义链,其中2'-O-甲基RNA单体位于沿上链而不是以上示意图中当前描绘的下链的交替残基上。
在另一实施方案中,DsiRNA包含:
5′-XXXXXXXXXXXXXXXXXXXXXXXXN*[X1/D1]NDD-3′
3′-YXXXXXXXXXXXXXXXXXXXXXXXXN*[X2/D2]NZZ-5’
其中“X”=RNA,“Y”是包含0-10个任选为2'-O-甲基RNA单体的RNA单体的任选存在的突出域–在某些实施方案中,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,“D”=DNA,“Z”=DNA或RNA,且“N”=1至50或更多,但任选为1-8或1-10,其中至少一个D1N存在于上链中,并与下链中的相应D2N碱基配对。任选地,D1N和D1N+1与相应D2N和D2N+1碱基配对;D1N、D1N+1和D1N+2与相应D2N、D1N+1和D1N+2等碱基配对。“N*”=0至15或更多,但任选为0、1、2、3、4、5或6。在一个实施方案中,上链是有义链,且下链是反义链。或者,下链是有义链,且上链是反义链,其中2'-O-甲基RNA单体位于沿上链而不是以上示意图中当前描绘的下链的交替残基上。
在本文所描绘的结构中,有义链或反义链中任一者的5'端可任选地包含磷酸基。
在另一实施方案中,DNA:DNA延伸的DsiRNA包含具有相同长度的链,这些链具有1-3个用以使Dicer裂解定向的错配残基(具体说来,当第一条链与第二条链相互退火时,DsiRNA第一条链上的1位、2位或3位(当从3'末端残基编号时)中的一者或多者与第二条链上5'末端区域的相应残基错配)。具有两个末端错配残基的示例性DNA:DNA延伸的DsiRNA试剂为如下所示:
其中“X”=RNA,“M”=当链退火时不与另一互补链的相应“M”残基碱基配对(形成氢键)的核酸残基(RNA、DNA或非天然或经过修饰的核酸),“D”=DNA且“N”=1至50或更多,但任选为1-8或1-10。“N*”=0至15或更多,但任选为0、1、2、3、4、5或6。此类试剂的任何残基可任选为2'-O-甲基RNA单体–从下(第二)链的3'末端残基开始,2'-O-甲基RNA单体的交替定位也可用于上述“平端/断裂”DsiRNA试剂中。在一个实施方案中,上链(第一链)是有义链,且下链(第二链)是反义链。或者,下链是有义链,且上链是反义链。类似于以上所示关于不对称/突出试剂的修饰和DNA:DNA延伸模式也可以并入所述“平端/断裂”试剂中。
在一个实施方案中,提供长度延伸的DsiRNA试剂,该DsiRNA试剂包含位于经过模拟以通过特异性引导Dicer裂解来起作用的位点的脱氧核糖核苷酸,而不需要在dsRNA结构中存在碱基配对的脱氧核糖核苷酸。此类分子的示例性结构如下所示:
5′-XXXXXXXXXXXXXXXXXXXDDXX-3′
3′-YXXXXXXXXXXXXXXXXXDDXXXX-5′
其中“X”=RNA,“Y”是包含0-10个任选为2'-O-甲基RNA单体的RNA单体的任选存在的突出域–在某些实施方案中,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且"D"=DNA。在一个实施方案中,上链是有义链,且下链是反义链。或者,下链是有义链,且上链是反义链。模拟上述结构以迫使Dicer在最低限度上裂解呈最初加工后形式的21mer双链体。在上述结构的下链是反义链的实施方案中,在反义链5'端最后一个和倒数第二个残基两个脱氧核糖核苷酸残基的定位很可能会减少脱靶效应(因为先前的研究已经显示至少从反义链5'末端倒数第二个位置的2'-O-甲基修饰会减少脱靶效应;参见例如,US2007/0223427)。
在一个实施方案中,DsiRNA包含下述(示例性“左侧延伸”、“DNA延伸的”DsiRNA):
5′-DNXXXXXXXXXXXXXXXXXXXXXXXXN*Y-3′
3′-DNXXXXXXXXXXXXXXXXXXXXXXXXN*-5’
其中“X”=RNA,“Y”是包含0-10个任选为2'-O-甲基RNA单体的RNA单体的任选存在的突出域–在某些实施方案中,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,"D"=DNA,且“N”=1至50或更多,但任选为1-8或1-10。“N*”=0至15或更多,但任选为0、1、2、3、4、5或6。在一个实施方案中,上链是有义链,且下链是反义链。或者,下链是有义链,且上链是反义链。
在相关实施方案中,DsiRNA包含:
5′-DNXXXXXXXXXXXXXXXXXXXXXXXXN*DD-3′
3′-DNXXXXXXXXXXXXXXXXXXXXXXXXN*XX-5'
其中“X”=RNA,任选为2'-O-甲基RNA单体,“D”=DNA,“N”=1至50或更多,但任选为1-8或1-10。“N*”=0至15或更多,但任选为0、1、2、3、4、5或6。在一个实施方案中,上链是有义链,且下链是反义链。或者,下链是有义链,且上链是反义链。
在另一实施方案中,DsiRNA包含:
5′-DNXXXXXXXXXXXXXXXXXXXXXXXXN*DD-3′
3′-DN XXXXXXXXXXXXXXXXXXXXXXXXN*ZZ-5'
其中“X”=RNA,任选为2'-O-甲基RNA单体,“D”=DNA,“N”=1至50或更多,但任选为1-8或1-10。“N*”=0至15或更多,但任选为0、1、2、3、4、5或6。“Z”=DNA或RNA。在一个实施方案中,上链是有义链,且下链是反义链。或者,下链是有义链,且上链是反义链,其中2'-O-甲基RNA单体位于沿上链而不是以上示意图中当前描绘的下链的交替残基上。
在另一此类实施方案中,DsiRNA包含:
5′-DNXXXXXXXXXXXXXXXXXXXXXXXXN*DD-3′
3′-DN XXXXXXXXXXXXXXXXXXXXXXXXN*ZZ-5'
其中“X”=RNA,任选为2'-O-甲基RNA单体,“D”=DNA,“N”=1至50或更多,但任选为1-8或1-10。“N*”=0至15或更多,但任选为0、1、2、3、4、5或6。“Z”=DNA或RNA。在一个实施方案中,上链是有义链,且下链是反义链。或者,下链是有义链,且上链是反义链,其中2'-O-甲基RNA单体位于沿上链而不是以上示意图中当前描绘的下链的交替残基上。
在另一此类实施方案中,DsiRNA包含:
5′-DNZZXXXXXXXXXXXXXXXXXXXXXXXXN*DD-3′
3′-DN XXXXXXXXXXXXXXXXXXXXXXXXXXN*ZZ-5’
其中“X”=RNA,“X”=2'-O-甲基RNA,“D”=DNA,“Z”=DNA或RNA,且“N”=1至50或更多,但任选为1-8或1-10。“N*”=0至15或更多,但任选为0、1、2、3、4、5或6。在一个实施方案中,上链是有义链,且下链是反义链。或者,下链是有义链,且上链是反义链,其中2'-O-甲基RNA单体位于沿上链而不是以上示意图中当前描绘的下链的交替残基上。
在另一此类实施方案中,DsiRNA包含:
5′-DNZZXXXXXXXXXXXXXXXXXXXXXXXXN*Y-3′
3′-DN XXXXXXXXXXXXXXXXXXXXXXXXXXN*-5’
其中“X”=RNA,“X”=2'-O-甲基RNA,“D”=DNA,“Z”=DNA或RNA,且“N”=1至50或更多,但任选为1-8或1-10。“N*”=0至15或更多,但任选为0、1、2、3、4、5或6。“Y”是包含0-10个任选为2'-O-甲基RNA单体的RNA单体的任选存在的突出域–在某些实施方案中,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体。在一个实施方案中,上链是有义链,且下链是反义链。或者,下链是有义链,且上链是反义链,其中2'-O-甲基RNA单体位于沿上链而不是以上示意图中当前描绘的下链的交替残基上。
在其它实施方案中,DsiRNA包含:
5′-[X1/D1]NXXXXXXXXXXXXXXXXXXXXXXXXN*DD-3′
3′-[X2/D2]NXXXXXXXXXXXXXXXXXXXXXXXXN*ZZ-5’
其中“X”=RNA,“D”=DNA,“Z”=DNA或RNA,且“N”=1至50或更多,但任选为1-8或1-10,其中至少一个D1N存在于上链中,并与下链中的相应D2N碱基配对。任选地,D1N和D1N+1与相应的D2N和D2N+1碱基配对;D1N、D1N+1和D1N+2与相应的D2N、D1N+1和D1N+2等碱基配对。“N*”=0至15或更多,但任选为0、1、2、3、4、5或6。在一个实施方案中,上链是有义链,且下链是反义链。或者,下链是有义链,且上链是反义链,其中2'-O-甲基RNA单体位于沿上链而不是以上示意图中当前描绘的下链的交替残基上。
在相关实施方案中,DsiRNA包含:
5′-[X1/D1]NXXXXXXXXXXXXXXXXXXXXXXXXN*Y-3′
3′-[X2/D2]NXXXXXXXXXXXXXXXXXXXXXXXXN*-5'
其中“X”=RNA,“D”=DNA,“Y”是包含0-10个任选为2'-O-甲基RNA单体的RNA单体的任选存在的突出域–在某些实施方案中,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且“N”=1至50或更多,但任选为1-8或1-10,其中至少一个D1N存在于上链中,并与下链中的相应D2N碱基配对。任选地,D1N和D1N+1与相应的D2N和D2N+1碱基配对;D1N、D1N+1和D1N+2与相应的D2N、D1N+1和D1N+2等碱基配对。“N*”=0至15或更多,但任选为0、1、2、3、4、5或6。在一个实施方案中,上链是有义链,且下链是反义链。或者,下链是有义链,且上链是反义链,其中2'-O-甲基RNA单体位于沿上链而不是以上示意图中当前描绘的下链的交替残基上。
在其它实施方案中,DNA:DNA延伸的DsiRNA包含具有相同长度的链,这些链具有1-3个用以使Dicer裂解定向的错配残基(具体说来,当第一条链与第二条链相互退火时,DsiRNA第一条链上的1位、2位或3位(当从3'末端残基编号时)中的一者或多者与第二条链上5'末端区域的相应残基错配)。具有两个末端错配残基的示例性DNA:DNA延伸的DsiRNA试剂如下所示:
其中“X”=RNA,“M”=当链退火时不与另一互补链的相应“M”残基碱基配对(形成氢键)的核酸残基(RNA、DNA或非天然或经过修饰的核酸),“D”=DNA且“N”=1至50或更多,但任选为1-8或1-10。“N*”=0至15或更多,但任选为0、1、2、3、4、5或6。此类试剂的任何残基可任选为2'-O-甲基RNA单体–从下(第二)链的3'末端残基开始,2'-O-甲基RNA单体的交替定位也可用于上述“平端/断裂”DsiRNA试剂中。在一个实施方案中,上链(第一链)是有义链,且下链(第二链)是反义链。或者,下链是有义链,且上链是反义链。类似于以上所示关于不对称/突出试剂的修饰和DNA:DNA延伸模式也可以并入所述“平端/断裂”试剂中。
在另一实施方案中,提供长度延伸的DsiRNA试剂,该DsiRNA试剂包含位于经过模拟以通过特异性引导Dicer裂解来起作用的位点的脱氧核糖核苷酸,而不需要在dsRNA结构中存在碱基配对的脱氧核糖核苷酸。此类分子的示例性结构如下所示:
5′-XXDDXXXXXXXXXXXXXXXXXXXXN*Y-3′
3′-DDXXXXXXXXXXXXXXXXXXXXXXN*-5′
其中“X”=RNA,“Y”是包含0-10个任选为2'-O-甲基RNA单体的RNA单体的任选存在的突出域–在某些实施方案中,“Y”是包含1-4个RNA单体的突出域,所述RNA单体任选为2'-O-甲基RNA单体,且“D”=DNA。“N*”=0至15或更多,但任选为0、1、2、3、4、5或6。在一个实施方案中,上链是有义链,且下链是反义链。或者,下链是有义链,且上链是反义链。模拟上述结构以迫使Dicer在最低限度上裂解呈最初加工后形式的21mer双链体。在上述结构的下链是反义链的实施方案中,在反义链5'端最后一个和倒数第二个残基的两个脱氧核糖核苷酸残基的定位很可能会减少脱靶效应(因为先前的研究已经显示至少在反义链5'末端倒数第二个位置的2'-O-甲基修饰会减少脱靶效应;参见例如,US2007/0223427)。
在某些实施方案中,上述结构的“D”残基包括至少一个PS-DNA或PS-RNA。任选地,上述结构的“D”残基包括至少一个抑制Dicer裂解的经过修饰的核苷酸。
虽然上述“DNA延伸的”DsiRNA试剂可归类为“左侧延伸的”或“右侧延伸的”,但也可以按本文关于“右侧延伸的”和“左侧延伸的”试剂所述类似的方式,产生和使用在单一试剂内同时包含左侧延伸的和右侧延伸的含DNA序列的DsiRNA试剂(例如,在核心dsRNA结构周围的两个侧翼都是dsDNA延伸)。
在一些实施方案中,本发明的DsiRNA进一步包含用以接合DNA:DNA延伸的DsiRNA试剂的有义链和反义链的连接部分或域。任选地,这样的连接部分域将有义链的3'端与反义链的5'端接合。连接部分可以是化学(非核苷酸)连接子,例如寡聚亚甲基二醇连接子、寡聚乙二醇连接子或其它本领域公认的连接部分。或者,连接子可以是核苷酸连接子,任选地包括延伸的环和/或四核苷酸环。
在一个实施方案中,DsiRNA试剂具有不对称结构,其中有义链的长度为25个碱基对,且反义链的长度为27个碱基对并具有1-4个碱基的3'-突出(例如,一个碱基的3'-突出、两个碱基的3'-突出、三个碱基的3'-突出或四个碱基的3'-突出)。在另一个实施方案中,此DsiRNA试剂具有不对称结构,其在有义链的3'端进一步含有2个脱氧核苷酸。
在另一实施方案中,DsiRNA试剂具有不对称结构,其中反义链的长度为25个碱基对,且有义链的长度为27个碱基对并具有1-4个碱基的3'-突出(例如,一个碱基的3'-突出、两个碱基的3'-突出、三个碱基的3'-突出或四个碱基的3'-突出)。在另一实施方案中,此DsiRNA试剂具有不对称结构,其在反义链的3'端进一步含有2个脱氧核苷酸。
本发明的示例性的KRAS靶向DsiRNA试剂包括下述:
KRAS-355靶位点
KRAS-940靶位点
KRAS-355*替代性(多形性)靶位点
本发明的其它示例性KRAS靶向DsiRNA试剂包括下述:
表2:抗KRAS DsiRNA试剂和同源siRNA试剂反义链
表3:示例性抗KRAS不对称DsiRNA试剂
5’-GUUGGAGCUGGUGGCGUAGGCAAga-3’(SEQ ID NO:91)
3’-AUCAACCUCGACCACCGCAUCCGUUCU-5’(SEQ ID NO:11)
KRAS-204靶:5'-TAGTTGGAGCTGGTGGCGTAGGCAAGA-3’(SEQ ID NO:141)
5’-GUUGGAGCUGUUGGCGUAGGCAAga-3’(SEQ ID NO:129)
3’-AUCAACCUCGACAACCGCAUCCGUUCU-5’(SEQ ID NO:135)
KRAS-204*靶:5'-TAGTTGGAGCTGTTGGCGTAGGCAAGA-3’(SEQ ID NO:142)
5’-UAUUCUCGACACAGCAGGUCAAGag-3’(SEQ ID NO:92)
3’-CUAUAAGAGCUGUGUCGUCCAGUUCUC-5’(SEQ ID NO:12)
KRAS-341靶:5'-GATATTCTCGACACAGCAGGTCAAGAG-3’(SEQ ID NO:143)
5’-UAUUCUCGACACAGCAGGUCAUGag-3’(SEQ ID NO:130)
3’-CUAUAAGAGCUGUGUCGUCCAGUACUC-5’(SEQ ID NO:136)
KRAS-341*靶:5'-GATATTCTCGACACAGCAGGTCATGAG-3’(SEQ ID NO:144)
5’-UUCUCGACACAGCAGGUCAAGAGga-3’(SEQ ID NO:93)
3’-AUAAGAGCUGUGUCGUCCAGUUCUCCU-5’(SEQ ID NO:13)
KRAS-343靶:5'-TATTCTCGACACAGCAGGTCAAGAGGA-3’(SEQ ID NO:145)
5’-UUCUCGACACAGCAGGUCAUGAGga-3’(SEQ ID NO:131)
3’-AUAAGAGCUGUGUCGUCCAGUACUCCU-5’(SEQ ID NO:137)
KRAS-343*靶:5'-TATTCTCGACACAGCAGGTCATGAGGA-3’(SEQ ID NO:146)
5’-CAGGUCAAGAGGAGUACAGUGCAat-3’(SEQ ID NO:5)
3’-UCGUCCAGUUCUCCUCAUGUCACGUUA-5’(SEQ ID NO:14)
KRAS-355靶:5'-AGCAGGTCAAGAGGAGTACAGTGCAAT-3’(SEQ ID NO:147)
5’-CAGGUCAUGAGGAGUACAGUGCAat-3’(SEQ ID NO:132)
3’-UCGUCCAGUACUCCUCAUGUCACGUUA-5’(SEQ ID NO:138)
KRAS-355*靶:5'-AGCAGGTCATGAGGAGTACAGTGCAAT-3’(SEQ ID NO:148)
5’-AAGAGGAGUACAGUGCAAUGAGGga-3’(SEQ ID NO:94)
3’-AGUUCUCCUCAUGUCACGUUACUCCCU-5’(SEQ ID NO:15)
KRAS-361靶:5'-TCAAGAGGAGTACAGTGCAATGAGGGA-3’(SEQ ID NO:149)
5’-AUGAGGAGUACAGUGCAAUGAGGga-3’(SEQ ID NO:133)
3’-AGUACUCCUCAUGUCACGUUACUCCCU-5’(SEQ ID NO:139)
KRAS-361*靶:5'-TCATGAGGAGTACAGTGCAATGAGGGA-3’(SEQ ID NO:150)
5’-CAGUGCAAUGAGGGACCAGUACAtg-3’(SEQ ID NO:95)
3’-AUGUCACGUUACUCCCUGGUCAUGUAC-5’(SEQ ID NO:16)
KRAS-371靶:5'-TACAGTGCAATGAGGGACCAGTACATG-3’(SEQ ID NO:151)
5’-UGGGGAGGGCUUUCUUUGUGUAUtt-3’(SEQ ID NO:96)
3’-UGACCCCUCCCGAAAGAAACACAUAAA-5’(SEQ ID NO:17)
KRAS-401靶:5'-ACTGGGGAGGGCTTTCTTTGTGTATTT-3’(SEQ ID NO:152)
5’-GGAGGGCUUUCUUUGUGUAUUUGcc-3’(SEQ ID NO:97)
3’-CCCCUCCCGAAAGAAACACAUAAACGG-5’(SEQ ID NO:18)
KRAS-404靶:5'-GGGGAGGGCTTTCTTTGTGTATTTGCC-3’(SEQ ID NO:153)
5’-AGGGCUUUCUUUGUGUAUUUGCCat-3’(SEQ ID NO:98)
3’-CCUCCCGAAAGAAACACAUAAACGGUA-5’(SEQ ID NO:19)
KRAS-406靶:5'-GGAGGGCTTTCTTTGTGTATTTGCCAT-3’(SEQ ID NO:154)
5’-CUUUCUUUGUGUAUUUGCCAUAAat-3’(SEQ ID NO:99)
3’-CCGAAAGAAACACAUAAACGGUAUUUA-5’(SEQ ID NO:20)
KRAS-410靶:5'-GGCTTTCTTTGTGTATTTGCCATAAAT-3’(SEQ ID NO:155)
5’-UUUGUGUAUUUGCCAUAAAUAAUac-3’(SEQ ID NO:100)
3’-AGAAACACAUAAACGGUAUUUAUUAUG-5’(SEQ ID NO:21)
KRAS-415靶:5'-TCTTTGTGTATTTGCCATAAATAATAC-3’(SEQ ID NO:156)
5’-UUGUGUAUUUGCCAUAAAUAAUAct-3’(SEQ ID NO:101)
3’-GAAACACAUAAACGGUAUUUAUUAUGA-5’(SEQ ID NO:22)
KRAS-416靶:5'-CTTTGTGTATTTGCCATAAATAATACT-3’(SEQ ID NO:157)
5’-UGUGUAUUUGCCAUAAAUAAUACta-3’(SEQ ID NO:102)
3’-AAACACAUAAACGGUAUUUAUUAUGAU-5’(SEQ ID NO:23)
KRAS-417靶:5'-TTTGTGTATTTGCCATAAATAATACTA-3’(SEQ ID NO:158)
5’-GUGUAUUUGCCAUAAAUAAUACUaa-3’(SEQ ID NO:103)
3’-AACACAUAAACGGUAUUUAUUAUGAUU-5’(SEQ ID NO:24)
KRAS-418靶:5'-TTGTGTATTTGCCATAAATAATACTAA-3’(SEQ ID NO:159)
5’-UGUAUUUGCCAUAAAUAAUACUAaa-3’(SEQ ID NO:104)
3’-ACACAUAAACGGUAUUUAUUAUGAUUU-5’(SEQ ID NO:25)
KRAS-419靶:5'-TGTGTATTTGCCATAAATAATACTAAA-3’(SEQ ID NO:160)
5’-GUAUUUGCCAUAAAUAAUACUAAat-3’(SEQ ID NO:105)
3’-CACAUAAACGGUAUUUAUUAUGAUUUA-5’(SEQ ID NO:26)
KRAS-420靶:5'-GTGTATTTGCCATAAATAATACTAAAT-3’(SEQ ID NO:161)
5’-AUAAAUAAUACUAAAUCAUUUGAag-3’(SEQ ID NO:106)
3’-GGUAUUUAUUAUGAUUUAGUAAACUUC-5’(SEQ ID NO:27)
KRAS-429靶:5'-CCATAAATAATACTAAATCATTTGAAG-3’(SEQ ID NO:162)
5’-UAAUACUAAAUCAUUUGAAGAUAtt-3’(SEQ ID NO:107)
3’-UUAUUAUGAUUUAGUAAACUUCUAUAA-5’(SEQ ID NO:28)
KRAS-434靶:5'-AATAATACTAAATCATTTGAAGATATT-3’(SEQ ID NO:163)
5’-ACUAAAUCAUUUGAAGAUAUUCAcc-3’(SEQ ID NO:108)
3’-UAUGAUUUAGUAAACUUCUAUAAGUGG-5’(SEQ ID NO:29)
KRAS-438靶:5'-ATACTAAATCATTTGAAGATATTCACC-3’(SEQ ID NO:164)
5’-UAAAUCAUUUGAAGAUAUUCACCat-3’(SEQ ID NO:109)
3’-UGAUUUAGUAAACUUCUAUAAGUGGUA-5’(SEQ ID NO:30)
KRAS-440靶:5'-ACTAAATCATTTGAAGATATTCACCAT-3’(SEQ ID NO:165)
5’-CAUUUGAAGAUAUUCACCAUUAUag-3’(SEQ ID NO:110)
3’-UAGUAAACUUCUAUAAGUGGUAAUAUC-5’(SEQ ID NO:31)
KRAS-445靶:5'-ATCATTTGAAGATATTCACCATTATAG-3’(SEQ ID NO:166)
5’-GAAGAUAUUCACCAUUAUAGAGAac-3’(SEQ ID NO:111)
3’-AACUUCUAUAAGUGGUAAUAUCUCUUG-5’(SEQ ID NO:32)
KRAS-450靶:5'-TTGAAGATATTCACCATTATAGAGAAC-3’(SEQ ID NO:167)
5’-AGAUAUUCACCAUUAUAGAGAACaa-3’(SEQ ID NO:112)
3’-CUUCUAUAAGUGGUAAUAUCUCUUGUU-5’(SEQ ID NO:33)
KRAS-452靶:5'-GAAGATATTCACCATTATAGAGAACAA-3’(SEQ ID NO:168)
5’-CUAUGGUCCUAGUAGGAAAUAAAtg-3’(SEQ ID NO:113)
3’-UGGAUACCAGGAUCAUCCUUUAUUUAC-5’(SEQ ID NO:34)
KRAS-508靶:5'-ACCTATGGTCCTAGTAGGAAATAAATG-3’(SEQ ID NO:169)
5’-GAUUUGCCUUCUAGAACAGUAGAca-3’(SEQ ID NO:114)
3’-CACUAAACGGAAGAUCUUGUCAUCUGU-5’(SEQ ID NO:35)
KRAS-534靶:5'-GTGATTTGCCTTCTAGAACAGTAGACA-3’(SEQ ID NO:170)
5’-GAUGAUGCCUUCUAUACAUUAGUtc-3’(SEQ ID NO:115)
3’-AACUACUACGGAAGAUAUGUAAUCAAG-5’(SEQ ID NO:36)
KRAS-760靶:5'-TTGATGATGCCTTCTATACATTAGTTC-3’(SEQ ID NO:171)
5’-CAUUAGUUCGAGAAAUUCGAAAAca-3’(SEQ ID NO:116)
3’-AUGUAAUCAAGCUCUUUAAGCUUUUGU-5’(SEQ ID NO:37)
KRAS-776靶:5'-TACATTAGTTCGAGAAATTCGAAAACA-3’(SEQ ID NO:172)
5’-AGAAAUUCGAAAACAUAAAGAAAag-3’(SEQ ID NO:117)
3’-GCUCUUUAAGCUUUUGUAUUUCUUUUC-5’(SEQ ID NO:38)
KRAS-786靶:5'-CGAGAAATTCGAAAACATAAAGAAAAG-3’(SEQ ID NO:173)
5’-AAAACAUAAAGAAAAGAUGAGCAaa-3’(SEQ ID NO:118)
3’-GCUUUUGUAUUUCUUUUCUACUCGUUU-5’(SEQ ID NO:39)
KRAS-795靶:5'-CGAAAACATAAAGAAAAGATGAGCAAA-3’(SEQ ID NO:174)
5’-AUAAAGAAAAGAUGAGCAAAGAUgg-3’(SEQ ID NO:119)
3’-UGUAUUUCUUUUCUACUCGUUUCUACC-5’(SEQ ID NO:40)
KRAS-800靶:5'-ACATAAAGAAAAGATGAGCAAAGATGG-3’(SEQ ID NO:175)
5’-AUAAAGAAAAGAUGAGCAAAGACgg-3’(SEQ ID NO:134)
3’-UGUAUUUCUUUUCUACUCGUUUCUGCC-5’(SEQ ID NO:140)
KRAS-800*靶:5'-ACATAAAGAAAAGATGAGCAAAGACGG-3’(SEQ ID NO:176)
5’-UUGUACAUUACACUAAAUUAUUAgc-3’(SEQ ID NO:120)
3’-AAAACAUGUAAUGUGAUUUAAUAAUCG-5’(SEQ ID NO:41)
KRAS-920靶:5'-TTTTGTACATTACACTAAATTATTAGC-3’(SEQ ID NO:177)
5’-AAUUAUUAGCAUUUGUUUUAGCAtt-3’(SEQ ID NO:121)
3’-AUUUAAUAAUCGUAAACAAAAUCGUAA-5’(SEQ ID NO:42)
KRAS-935靶:5'-TAAATTATTAGCATTTGTTTTAGCATT-3’(SEQ ID NO:178)
5’-UUAGCAUUUGUUUUAGCAUUACCta-3’(SEQ ID NO:8)
3’-AUAAUCGUAAACAAAAUCGUAAUGGAU-5’(SEQ ID NO:43)
KRAS-940靶:5'-TATTAGCATTTGTTTTAGCATTACCTA-3’(SEQ ID NO:179)
5’-AGUUUUUUUUUCCUCUAAGUGCCag-3’(SEQ ID NO:122)
3’-CUUCAAAAAAAAAGGAGAUUCACGGUC-5’(SEQ ID NO:44)
KRAS-1032靶:5'-GAAGTTTTTTTTTCCTCTAAGTGCCAG-3’(SEQ ID NO:180)
5’-AAGUGCCAGUAUUCCCAGAGUUUtg-3’(SEQ ID NO:123)
3’-GAUUCACGGUCAUAAGGGUCUCAAAAC-5’(SEQ ID NO:45)
KRAS-1048靶:5'-CTAAGTGCCAGTATTCCCAGAGTTTTG-3’(SEQ ID NO:181)
5’-GGUGUGAAACAAAUUAAUGAAGCtt-3’(SEQ ID NO:124)
3’-AACCACACUUUGUUUAAUUACUUCGAA-5’(SEQ ID NO:46)
KRAS-1188靶:5'-TTGGTGTGAAACAAATTAATGAAGCTT-3’(SEQ ID NO:182)
5’-AUUAAUUACUAAUUUCAGUUGAGac-3’(SEQ ID NO:125)
3’-CCUAAUUAAUGAUUAAAGUCAACUCUG-5’(SEQ ID NO:47)
KRAS-1256靶:5'-GGATTAATTACTAATTTCAGTTGAGAC-3’(SEQ ID NO:183)
5’-UAUAUUUACAUGCUACUAAAUUUtt-3’(SEQ ID NO:126)
3’-CGAUAUAAAUGUACGAUGAUUUAAAAA-5’(SEQ ID NO:48)
KRAS-1634靶:5'-GCTATATTTACATGCTACTAAATTTTT-3’(SEQ ID NO:184)
5’-UUUAACUAUUUUUGUAUAGUGUAaa-3’(SEQ ID NO:127)
3’-UAAAAUUGAUAAAAACAUAUCACAUUU-5’(SEQ ID NO:49)
KRAS-5134靶:5'-ATTTTAACTATTTTTGTATAGTGTAAA-3’(SEQ ID NO:185)
5’-CAGUGUGAUCCAGUUGUUUUCCAtc-3’(SEQ ID NO:128)
3’-ACGUCACACUAGGUCAACAAAAGGUAG-5’(SEQ ID NO:50)
KRAS-5208靶:5'-TGCAGTGTGATCCAGTTGTTTTCCATC-3’(SEQ ID NO:186)表4:其它优选的抗KRAS不对称DsiRNA试剂
5'-CUGAAAAUGACUGAAUAUAAACUtg-3'(SEQ ID NO:892)
3'-ACGACUUUUACUGACUUAUAUUUGAAC-5'(SEQ ID NO:189)
KRAS-174靶:5'-TGCTGAAAATGACTGAATATAAACTTG-3'(SEQ ID NO:1595)
5'-AUGACUGAAUAUAAACUUGUGGUag-3'(SEQ ID NO:893)
3'-UUUACUGACUUAUAUUUGAACACCAUC-5'(SEQ ID NO:190)
KRAS-180靶:5'-AAATGACTGAATATAAACTTGTGGTAG-3'(SEQ ID NO:1596)
5'-CUGAAUAUAAACUUGUGGUAGUUgg-3'(SEQ ID NO:894)
3'-CUGACUUAUAUUUGAACACCAUCAACC-5'(SEQ ID NO:191)
KRAS-184靶:5'-GACTGAATATAAACTTGTGGTAGTTGG-3'(SEQ ID NO:1597)
5'-CUAAUUCAGAAUCAUUUUGUGGAcg-3'(SEQ ID NO:895)
3'-UCGAUUAAGUCUUAGUAAAACACCUGC-5'(SEQ ID NO:192)
KRAS-246靶:5'-AGCTAATTCAGAATCATTTTGTGGACG-3'(SEQ ID NO:1598)
5'-GAAUAUGAUCCAACAAUAGAGGAtt-3'(SEQ ID NO:896)
3'-UGCUUAUACUAGGUUGUUAUCUCCUAA-5'(SEQ ID NO:193)
KRAS-270靶:5'-ACGAATATGATCCAACAATAGAGGATT-3'(SEQ ID NO:1599)
5'-CAAGUAGUAAUUGAUGGAGAAACct-3'(SEQ ID NO:897)
3'-UCGUUCAUCAUUAACUACCUCUUUGGA-5'(SEQ ID NO:194)
KRAS-306靶:5'-AGCAAGTAGTAATTGATGGAGAAACCT-3'(SEQ ID NO:1600)
5'-AGGGCUUUCUUUGUGUAUUUGCCat-3'(SEQ ID NO:898)
3'-CCUCCCGAAAGAAACACAUAAACGGUA-5'(SEQ ID NO:195)
KRAS-406靶:5'-GGAGGGCTTTCTTTGTGTATTTGCCAT-3'(SEQ ID NO:1601)
5'-UUUGUGUAUUUGCCAUAAAUAAUac-3'(SEQ ID NO:899)
3'-AGAAACACAUAAACGGUAUUUAUUAUG-5'(SEQ ID NO:196)
KRAS-415靶:5'-TCTTTGTGTATTTGCCATAAATAATAC-3'(SEQ ID NO:1602)
5'-UUGUGUAUUUGCCAUAAAUAAUAct-3'(SEQ ID NO:900)
3'-GAAACACAUAAACGGUAUUUAUUAUGA-5'(SEQ ID NO:197)
KRAS-416靶:5'-CTTTGTGTATTTGCCATAAATAATACT-3'(SEQ ID NO:1603)
5'-UGUGUAUUUGCCAUAAAUAAUACta-3'(SEQ ID NO:901)
3'-AAACACAUAAACGGUAUUUAUUAUGAU-5'(SEQ ID NO:198)
KRAS-417靶:5'-TTTGTGTATTTGCCATAAATAATACTA-3'(SEQ ID NO:1604)
5'-GUGUAUUUGCCAUAAAUAAUACUaa-3'(SEQ ID NO:902)
3'-AACACAUAAACGGUAUUUAUUAUGAUU-5'(SEQ ID NO:199)
KRAS-418靶:5'-TTGTGTATTTGCCATAAATAATACTAA-3'(SEQ ID NO:1605)
5'-AUUUGCCAUAAAUAAUACUAAAUca-3'(SEQ ID NO:903)
3'-CAUAAACGGUAUUUAUUAUGAUUUAGU-5'(SEQ ID NO:200)
KRAS-422靶:5'-GTATTTGCCATAAATAATACTAAATCA-3'(SEQ ID NO:1606)
5'-UUUGCCAUAAAUAAUACUAAAUCat-3'(SEQ ID NO:904)
3'-AUAAACGGUAUUUAUUAUGAUUUAGUA-5'(SEQ ID NO:201)
KRAS-423靶:5'-TATTTGCCATAAATAATACTAAATCAT-3'(SEQ ID NO:1607)
5'-AUAAAUAAUACUAAAUCAUUUGAag-3'(SEQ ID NO:905)
3'-GGUAUUUAUUAUGAUUUAGUAAACUUC-5'(SEQ ID NO:202)
KRAS-429靶:5'-CCATAAATAATACTAAATCATTTGAAG-3'(SEQ ID NO:1608)
5'-UAAAUAAUACUAAAUCAUUUGAAga-3'(SEQ ID NO:906)
3'-GUAUUUAUUAUGAUUUAGUAAACUUCU-5'(SEQ ID NO:203)
KRAS-430靶:5'-CATAAATAATACTAAATCATTTGAAGA-3'(SEQ ID NO:1609)
5'-AAUAAUACUAAAUCAUUUGAAGAta-3'(SEQ ID NO:907)
3'-AUUUAUUAUGAUUUAGUAAACUUCUAU-5'(SEQ ID NO:204)
KRAS-432靶:5'-TAAATAATACTAAATCATTTGAAGATA-3'(SEQ ID NO:1610)
5'-AUAAUACUAAAUCAUUUGAAGAUat-3'(SEQ ID NO:908)
3'-UUUAUUAUGAUUUAGUAAACUUCUAUA-5'(SEQ ID NO:205)
KRAS-433靶:5'-AAATAATACTAAATCATTTGAAGATAT-3'(SEQ ID NO:1611)
5'-UAAUACUAAAUCAUUUGAAGAUAtt-3'(SEQ ID NO:909)
3'-UUAUUAUGAUUUAGUAAACUUCUAUAA-5'(SEQ ID NO:206)
KRAS-434靶:5'-AATAATACTAAATCATTTGAAGATATT-3'(SEQ ID NO:1612)
5'-AAUACUAAAUCAUUUGAAGAUAUtc-3'(SEQ ID NO:910)
3'-UAUUAUGAUUUAGUAAACUUCUAUAAG-5'(SEQ ID NO:207)
KRAS-435靶:5'-ATAATACTAAATCATTTGAAGATATTC-3'(SEQ ID NO:1613)
5'-UUGAAGAUAUUCACCAUUAUAGAga-3'(SEQ ID NO:911)
3'-UAAACUUCUAUAAGUGGUAAUAUCUCU-5'(SEQ ID NO:208)
KRAS-448靶:5'-ATTTGAAGATATTCACCATTATAGAGA-3'(SEQ ID NO:1614)
5'-GAAGAUAUUCACCAUUAUAGAGAac-3'(SEQ ID NO:912)
3'-AACUUCUAUAAGUGGUAAUAUCUCUUG-5'(SEQ ID NO:209)
KRAS-450靶:5'-TTGAAGATATTCACCATTATAGAGAAC-3'(SEQ ID NO:1615)
5'-AAGAUAUUCACCAUUAUAGAGAAca-3'(SEQ ID NO:913)
3'-ACUUCUAUAAGUGGUAAUAUCUCUUGU-5'(SEQ ID NO:210)
KRAS-451靶:5'-TGAAGATATTCACCATTATAGAGAACA-3'(SEQ ID NO:1616)
5'-AGAUAUUCACCAUUAUAGAGAACaa-3'(SEQ ID NO:914)
3'-CUUCUAUAAGUGGUAAUAUCUCUUGUU-5'(SEQ ID NO:211)
KRAS-452靶:5'-GAAGATATTCACCATTATAGAGAACAA-3'(SEQ ID NO:1617)
5'-GAUAUUCACCAUUAUAGAGAACAaa-3'(SEQ ID NO:915)
3'-UUCUAUAAGUGGUAAUAUCUCUUGUUU-5'(SEQ ID NO:212)
KRAS-453靶:5'-AAGATATTCACCATTATAGAGAACAAA-3'(SEQ ID NO:1618)
5'-AUUAUAGAGAACAAAUUAAAAGAgt-3'(SEQ ID NO:916)
3'-GGUAAUAUCUCUUGUUUAAUUUUCUCA-5'(SEQ ID NO:213)
KRAS-463靶:5'-CCATTATAGAGAACAAATTAAAAGAGT-3'(SEQ ID NO:1619)
5'-UAUAGAGAACAAAUUAAAAGAGUta-3'(SEQ ID NO:917)
3'-UAAUAUCUCUUGUUUAAUUUUCUCAAU-5'(SEQ ID NO:214)
KRAS-465靶:5'-ATTATAGAGAACAAATTAAAAGAGTTA-3'(SEQ ID NO:1620)
5'-AUAGAGAACAAAUUAAAAGAGUUaa-3'(SEQ ID NO:918)
3'-AAUAUCUCUUGUUUAAUUUUCUCAAUU-5'(SEQ ID NO:215)
KRAS-466靶:5'-TTATAGAGAACAAATTAAAAGAGTTAA-3'(SEQ ID NO:1621)
5'-UAGAGAACAAAUUAAAAGAGUUAag-3'(SEQ ID NO:919)
3'-AUAUCUCUUGUUUAAUUUUCUCAAUUC-5'(SEQ ID NO:216)
KRAS-467靶:5'-TATAGAGAACAAATTAAAAGAGTTAAG-3'(SEQ ID NO:1622)
5'-AGAGAACAAAUUAAAAGAGUUAAgg-3'(SEQ ID NO:920)
3'-UAUCUCUUGUUUAAUUUUCUCAAUUCC-5'(SEQ ID NO:217)
KRAS-468靶:5'-ATAGAGAACAAATTAAAAGAGTTAAGG-3'(SEQ ID NO:1623)
5'-AGUAGGAAAUAAAUGUGAUUUGCct-3'(SEQ ID NO:921)
3'-GAUCAUCCUUUAUUUACACUAAACGGA-5'(SEQ ID NO:218)
KRAS-518靶:5'-CTAGTAGGAAATAAATGTGATTTGCCT-3'(SEQ ID NO:1624)
5'-GUAGGAAAUAAAUGUGAUUUGCCtt-3'(SEQ ID NO:922)
3'-AUCAUCCUUUAUUUACACUAAACGGAA-5'(SEQ ID NO:219)
KRAS-519靶:5'-TAGTAGGAAATAAATGTGATTTGCCTT-3'(SEQ ID NO:1625)
5'-GAAGUUAUGGAAUUCCUUUUAUUga-3'(SEQ ID NO:923)
3'-UUCUUCAAUACCUUAAGGAAAAUAACU-5'(SEQ ID NO:220)
KRAS-583靶:5'-AAGAAGTTATGGAATTCCTTTTATTGA-3'(SEQ ID NO:1626)
5'-GUUAUGGAAUUCCUUUUAUUGAAac-3'(SEQ ID NO:924)
3'-UUCAAUACCUUAAGGAAAAUAACUUUG-5'(SEQ ID NO:221)
KRAS-586靶:5'-AAGTTATGGAATTCCTTTTATTGAAAC-3'(SEQ ID NO:1627)
5'-UUAUGGAAUUCCUUUUAUUGAAAca-3'(SEQ ID NO:925)
3'-UCAAUACCUUAAGGAAAAUAACUUUGU-5'(SEQ ID NO:222)
KRAS-587靶:5'-AGTTATGGAATTCCTTTTATTGAAACA-3'(SEQ ID NO:1628)
5'-UAUGGAAUUCCUUUUAUUGAAACat-3'(SEQ ID NO:926)
3'-CAAUACCUUAAGGAAAAUAACUUUGUA-5'(SEQ ID NO:223)
KRAS-588靶:5'-GTTATGGAATTCCTTTTATTGAAACAT-3'(SEQ ID NO:1629)
5'-AUGGAAUUCCUUUUAUUGAAACAtc-3'(SEQ ID NO:927)
3'-AAUACCUUAAGGAAAAUAACUUUGUAG-5'(SEQ ID NO:224)
KRAS-589靶:5'-TTATGGAATTCCTTTTATTGAAACATC-3'(SEQ ID NO:1630)
5'-GAGGAUGCUUUUUAUACAUUGGUga-3'(SEQ ID NO:928)
3'-ACCUCCUACGAAAAAUAUGUAACCACU-5'(SEQ ID NO:225)
KRAS-636靶:5'-TGGAGGATGCTTTTTATACATTGGTGA-3'(SEQ ID NO:1631)
5'-GGAUGCUUUUUAUACAUUGGUGAgg-3'(SEQ ID NO:929)
3'-CUCCUACGAAAAAUAUGUAACCACUCC-5'(SEQ ID NO:226)
KRAS-638靶:5'-GAGGATGCTTTTTATACATTGGTGAGG-3'(SEQ ID NO:1632)
5'-AGAUUGAAAAAAAUCAGCAAAGAag-3'(SEQ ID NO:930)
3'-UGUCUAACUUUUUUUAGUCGUUUCUUC-5'(SEQ ID NO:227)
KRAS-678靶:5'-ACAGATTGAAAAAAATCAGCAAAGAAG-3'(SEQ ID NO:1633)
5'-GAUUGAAAAAAAUCAGCAAAGAAga-3'(SEQ ID NO:931)
3'-GUCUAACUUUUUUUAGUCGUUUCUUCU-5'(SEQ ID NO:228)
KRAS-679靶:5'-CAGATTGAAAAAAATCAGCAAAGAAGA-3'(SEQ ID NO:1634)
5'-UUGAAAAAAAUCAGCAAAGAAGAaa-3'(SEQ ID NO:932)
3'-CUAACUUUUUUUAGUCGUUUCUUCUUU-5'(SEQ ID NO:229)
KRAS-681靶:5'-GATTGAAAAAAATCAGCAAAGAAGAAA-3'(SEQ ID NO:1635)
5'-UGAAAAAAAUCAGCAAAGAAGAAaa-3'(SEQ ID NO:933)
3'-UAACUUUUUUUAGUCGUUUCUUCUUUU-5'(SEQ ID NO:230)
KRAS-682靶:5'-ATTGAAAAAAATCAGCAAAGAAGAAAA-3'(SEQ ID NO:1636)
5'-GAAAAAAAUCAGCAAAGAAGAAAag-3'(SEQ ID NO:934)
3'-AACUUUUUUUAGUCGUUUCUUCUUUUC-5'(SEQ ID NO:231)
KRAS-683靶:5'-TTGAAAAAAATCAGCAAAGAAGAAAAG-3'(SEQ ID NO:1637)
5'-AAAAAAAUCAGCAAAGAAGAAAAga-3'(SEQ ID NO:935)
3'-ACUUUUUUUAGUCGUUUCUUCUUUUCU-5'(SEQ ID NO:232)
KRAS-684靶:5'-TGAAAAAAATCAGCAAAGAAGAAAAGA-3'(SEQ ID NO:1638)
5'-CUGGCUGUGUGAAAAUUAAAAAAtg-3'(SEQ ID NO:936)
3'-AGGACCGACACACUUUUAAUUUUUUAC-5'(SEQ ID NO:233)
KRAS-712靶:5'-TCCTGGCTGTGTGAAAATTAAAAAATG-3'(SEQ ID NO:1639)
5'-CUGUGUGAAAAUUAAAAAAUGCAtt-3'(SEQ ID NO:937)
3'-CCGACACACUUUUAAUUUUUUACGUAA-5'(SEQ ID NO:234)
KRAS-716靶:5'-GGCTGTGTGAAAATTAAAAAATGCATT-3'(SEQ ID NO:1640)
5'-GUGAAAAUUAAAAAAUGCAUUAUaa-3'(SEQ ID NO:938)
3'-CACACUUUUAAUUUUUUACGUAAUAUU-5'(SEQ ID NO:235)
KRAS-720靶:5'-GTGTGAAAATTAAAAAATGCATTATAA-3'(SEQ ID NO:1641)
5'-UGAAAAUUAAAAAAUGCAUUAUAat-3'(SEQ ID NO:939)
3'-ACACUUUUAAUUUUUUACGUAAUAUUA-5'(SEQ ID NO:236)
KRAS-721靶:5'-TGTGAAAATTAAAAAATGCATTATAAT-3'(SEQ ID NO:1642)
5'-GAAAAUUAAAAAAUGCAUUAUAAtg-3'(SEQ ID NO:940)
3'-CACUUUUAAUUUUUUACGUAAUAUUAC-5'(SEQ ID NO:237)
KRAS-722靶:5'-GTGAAAATTAAAAAATGCATTATAATG-3'(SEQ ID NO:1643)
5'-AAAAUUAAAAAAUGCAUUAUAAUgt-3'(SEQ ID NO:941)
3'-ACUUUUAAUUUUUUACGUAAUAUUACA-5'(SEQ ID NO:238)
KRAS-723靶:5'-TGAAAATTAAAAAATGCATTATAATGT-3'(SEQ ID NO:1644)
5'-AAUUAAAAAAUGCAUUAUAAUGUaa-3'(SEQ ID NO:942)
3'-UUUUAAUUUUUUACGUAAUAUUACAUU-5'(SEQ ID NO:239)
KRAS-725靶:5'-AAAATTAAAAAATGCATTATAATGTAA-3'(SEQ ID NO:1645)
5'-AUUAAAAAAUGCAUUAUAAUGUAat-3'(SEQ ID NO:943)
3'-UUUAAUUUUUUACGUAAUAUUACAUUA-5'(SEQ ID NO:240)
KRAS-726靶:5'-AAATTAAAAAATGCATTATAATGTAAT-3'(SEQ ID NO:1646)
5'-UUAAAAAAUGCAUUAUAAUGUAAtc-3'(SEQ ID NO:944)
3'-UUAAUUUUUUACGUAAUAUUACAUUAG-5'(SEQ ID NO:241)
KRAS-727靶:5'-AATTAAAAAATGCATTATAATGTAATC-3'(SEQ ID NO:1647)
5'-UAAAAAAUGCAUUAUAAUGUAAUct-3'(SEQ ID NO:945)
3'-UAAUUUUUUACGUAAUAUUACAUUAGA-5'(SEQ ID NO:242)
KRAS-728靶:5'-ATTAAAAAATGCATTATAATGTAATCT-3'(SEQ ID NO:1648)
5'-AAAAAUGCAUUAUAAUGUAAUCUgg-3'(SEQ ID NO:946)
3'-AUUUUUUACGUAAUAUUACAUUAGACC-5'(SEQ ID NO:243)
KRAS-730靶:5'-TAAAAAATGCATTATAATGTAATCTGG-3'(SEQ ID NO:1649)
5'-CAUUAUAAUGUAAUCUGGGUGUUga-3'(SEQ ID NO:947)
3'-ACGUAAUAUUACAUUAGACCCACAACU-5'(SEQ ID NO:244)
KRAS-737靶:5'-TGCATTATAATGTAATCTGGGTGTTGA-3'(SEQ ID NO:1650)
5'-CGAGAAAUUCGAAAACAUAAAGAaa-3'(SEQ ID NO:948)
3'-AAGCUCUUUAAGCUUUUGUAUUUCUUU-5'(SEQ ID NO:245)
KRAS-784靶:5'-TTCGAGAAATTCGAAAACATAAAGAAA-3'(SEQ ID NO:1651)
5'-GAGAAAUUCGAAAACAUAAAGAAaa-3'(SEQ ID NO:949)
3'-AGCUCUUUAAGCUUUUGUAUUUCUUUU-5'(SEQ ID NO:246)
KRAS-785靶:5'-TCGAGAAATTCGAAAACATAAAGAAAA-3'(SEQ ID NO:1652)
5'-AGAAAUUCGAAAACAUAAAGAAAag-3'(SEQ ID NO:950)
3'-GCUCUUUAAGCUUUUGUAUUUCUUUUC-5'(SEQ ID NO:247)
KRAS-786靶:5'-CGAGAAATTCGAAAACATAAAGAAAAG-3'(SEQ ID NO:1653)
5'-AAUUCGAAAACAUAAAGAAAAGAtg-3'(SEQ ID NO:951)
3'-CUUUAAGCUUUUGUAUUUCUUUUCUAC-5'(SEQ ID NO:248)
KRAS-789靶:5'-GAAATTCGAAAACATAAAGAAAAGATG-3'(SEQ ID NO:1654)
5'-GAAAACAUAAAGAAAAGAUGAGCaa-3'(SEQ ID NO:952)
3'-AGCUUUUGUAUUUCUUUUCUACUCGUU-5'(SEQ ID NO:249)
KRAS-794靶:5'-TCGAAAACATAAAGAAAAGATGAGCAA-3'(SEQ ID NO:1655)
5'-AAAACAUAAAGAAAAGAUGAGCAaa-3'(SEQ ID NO:953)
3'-GCUUUUGUAUUUCUUUUCUACUCGUUU-5'(SEQ ID NO:250)
KRAS-795靶:5'-CGAAAACATAAAGAAAAGATGAGCAAA-3'(SEQ ID NO:1656)
5'-AGAUGGUAAAAAGAAGAAAAAGAag-3'(SEQ ID NO:954)
3'-UUUCUACCAUUUUUCUUCUUUUUCUUC-5'(SEQ ID NO:251)
KRAS-819靶:5'-AAAGATGGTAAAAAGAAGAAAAAGAAG-3'(SEQ ID NO:1657)
5'-GAUGGUAAAAAGAAGAAAAAGAAgt-3'(SEQ ID NO:955)
3'-UUCUACCAUUUUUCUUCUUUUUCUUCA-5'(SEQ ID NO:252)
KRAS-820靶:5'-AAGATGGTAAAAAGAAGAAAAAGAAGT-3'(SEQ ID NO:1658)
5'-UGGUAAAAAGAAGAAAAAGAAGUca-3'(SEQ ID NO:956)
3'-CUACCAUUUUUCUUCUUUUUCUUCAGU-5'(SEQ ID NO:253)
KRAS-822靶:5'-GATGGTAAAAAGAAGAAAAAGAAGTCA-3'(SEQ ID NO:1659)
5'-GGUAAAAAGAAGAAAAAGAAGUCaa-3'(SEQ ID NO:957)
3'-UACCAUUUUUCUUCUUUUUCUUCAGUU-5'(SEQ ID NO:254)
KRAS-823靶:5'-ATGGTAAAAAGAAGAAAAAGAAGTCAA-3'(SEQ ID NO:1660)
5'-AAAGAAGAAAAAGAAGUCAAAGAca-3'(SEQ ID NO:958)
3'-UUUUUCUUCUUUUUCUUCAGUUUCUGU-5'(SEQ ID NO:255)
KRAS-828靶:5'-AAAAAGAAGAAAAAGAAGTCAAAGACA-3'(SEQ ID NO:1661)
5'-AAGAAGAAAAAGAAGUCAAAGACaa-3'(SEQ ID NO:959)
3'-UUUUCUUCUUUUUCUUCAGUUUCUGUU-5'(SEQ ID NO:256)
KRAS-829靶:5'-AAAAGAAGAAAAAGAAGTCAAAGACAA-3'(SEQ ID NO:1662)
5'-AGAAGAAAAAGAAGUCAAAGACAaa-3'(SEQ ID NO:960)
3'-UUUCUUCUUUUUCUUCAGUUUCUGUUU-5'(SEQ ID NO:257)
KRAS-830靶:5'-AAAGAAGAAAAAGAAGTCAAAGACAAA-3'(SEQ ID NO:1663)
5'-AAAGACAAAGUGUGUAAUUAUGUaa-3'(SEQ ID NO:961)
3'-AGUUUCUGUUUCACACAUUAAUACAUU-5'(SEQ ID NO:258)
KRAS-846靶:5'-TCAAAGACAAAGTGTGTAATTATGTAA-3'(SEQ ID NO:1664)
5'-AAGACAAAGUGUGUAAUUAUGUAaa-3'(SEQ ID NO:962)
3'-GUUUCUGUUUCACACAUUAAUACAUUU-5'(SEQ ID NO:259)
KRAS-847靶:5'-CAAAGACAAAGTGTGTAATTATGTAAA-3'(SEQ ID NO:1665)
5'-CAAAGUGUGUAAUUAUGUAAAUAca-3'(SEQ ID NO:963)
3'-CUGUUUCACACAUUAAUACAUUUAUGU-5'(SEQ ID NO:260)
KRAS-851靶:5'-GACAAAGTGTGTAATTATGTAAATACA-3'(SEQ ID NO:1666)
5'-AAGUGUGUAAUUAUGUAAAUACAat-3'(SEQ ID NO:964)
3'-GUUUCACACAUUAAUACAUUUAUGUUA-5'(SEQ ID NO:261)
KRAS-853靶:5'-CAAAGTGTGTAATTATGTAAATACAAT-3'(SEQ ID NO:1667)
5'-GUGUAAUUAUGUAAAUACAAUUUgt-3'(SEQ ID NO:965)
3'-CACACAUUAAUACAUUUAUGUUAAACA-5'(SEQ ID NO:262)
KRAS-857靶:5'-GTGTGTAATTATGTAAATACAATTTGT-3'(SEQ ID NO:1668)
5'-GUAAUUAUGUAAAUACAAUUUGUac-3'(SEQ ID NO:966)
3'-CACAUUAAUACAUUUAUGUUAAACAUG-5'(SEQ ID NO:263)
KRAS-859靶:5'-GTGTAATTATGTAAATACAATTTGTAC-3'(SEQ ID NO:1669)
5'-AAUUAUGUAAAUACAAUUUGUACtt-3'(SEQ ID NO:967)
3'-CAUUAAUACAUUUAUGUUAAACAUGAA-5'(SEQ ID NO:264)
KRAS-861靶:5'-GTAATTATGTAAATACAATTTGTACTT-3'(SEQ ID NO:1670)
5'-AUUAUGUAAAUACAAUUUGUACUtt-3'(SEQ ID NO:968)
3'-AUUAAUACAUUUAUGUUAAACAUGAAA-5'(SEQ ID NO:265)
KRAS-862靶:5'-TAATTATGTAAATACAATTTGTACTTT-3'(SEQ ID NO:1671)
5'-UGUAAAUACAAUUUGUACUUUUUtc-3'(SEQ ID NO:969)
3'-AUACAUUUAUGUUAAACAUGAAAAAAG-5'(SEQ ID NO:266)
KRAS-866靶:5'-TATGTAAATACAATTTGTACTTTTTTC-3'(SEQ ID NO:1672)
5'-GUAAAUACAAUUUGUACUUUUUUct-3'(SEQ ID NO:970)
3'-UACAUUUAUGUUAAACAUGAAAAAAGA-5'(SEQ ID NO:267)
KRAS-867靶:5'-ATGTAAATACAATTTGTACTTTTTTCT-3'(SEQ ID NO:1673)
5'-UAAAUACAAUUUGUACUUUUUUCtt-3'(SEQ ID NO:971)
3'-ACAUUUAUGUUAAACAUGAAAAAAGAA-5'(SEQ ID NO:268)
KRAS-868靶:5'-TGTAAATACAATTTGTACTTTTTTCTT-3'(SEQ ID NO:1674)
5'-AAAUACAAUUUGUACUUUUUUCUta-3'(SEQ ID NO:972)
3'-CAUUUAUGUUAAACAUGAAAAAAGAAU-5'(SEQ ID NO:269)
KRAS-869靶:5'-GTAAATACAATTTGTACTTTTTTCTTA-3'(SEQ ID NO:1675)
5'-AAUUUGUACUUUUUUCUUAAGGCat-3'(SEQ ID NO:973)
3'-UGUUAAACAUGAAAAAAGAAUUCCGUA-5'(SEQ ID NO:270)
KRAS-875靶:5'-ACAATTTGTACTTTTTTCTTAAGGCAT-3'(SEQ ID NO:1676)
5'-AUUUGUACUUUUUUCUUAAGGCAta-3'(SEQ ID NO:974)
3'-GUUAAACAUGAAAAAAGAAUUCCGUAU-5'(SEQ ID NO:271)
KRAS-876靶:5'-CAATTTGTACTTTTTTCTTAAGGCATA-3'(SEQ ID NO:1677)
5'-CUAGUACAAGUGGUAAUUUUUGUac-3'(SEQ ID NO:975)
3'-AUGAUCAUGUUCACCAUUAAAAACAUG-5'(SEQ ID NO:272)
KRAS-901靶:5'-TACTAGTACAAGTGGTAATTTTTGTAC-3'(SEQ ID NO:1678)
5'-UAGUACAAGUGGUAAUUUUUGUAca-3'(SEQ ID NO:976)
3'-UGAUCAUGUUCACCAUUAAAAACAUGU-5'(SEQ ID NO:273)
KRAS-902靶:5'-ACTAGTACAAGTGGTAATTTTTGTACA-3'(SEQ ID NO:1679)
5'-AAGUGGUAAUUUUUGUACAUUACac-3'(SEQ ID NO:977)
3'-UGUUCACCAUUAAAAACAUGUAAUGUG-5'(SEQ ID NO:274)
KRAS-908靶:5'-ACAAGTGGTAATTTTTGTACATTACAC-3'(SEQ ID NO:1680)
5'-AGUGGUAAUUUUUGUACAUUACAct-3'(SEQ ID NO:978)
3'-GUUCACCAUUAAAAACAUGUAAUGUGA-5'(SEQ ID NO:275)
KRAS-909靶:5'-CAAGTGGTAATTTTTGTACATTACACT-3'(SEQ ID NO:1681)
5'-AUUUUUGUACAUUACACUAAAUUat-3'(SEQ ID NO:979)
3'-AUUAAAAACAUGUAAUGUGAUUUAAUA-5'(SEQ ID NO:276)
KRAS-916靶:5'-TAATTTTTGTACATTACACTAAATTAT-3'(SEQ ID NO:1682)
5'-UUUUUGUACAUUACACUAAAUUAtt-3'(SEQ ID NO:980)
3'-UUAAAAACAUGUAAUGUGAUUUAAUAA-5'(SEQ ID NO:277)
KRAS-917靶:5'-AATTTTTGTACATTACACTAAATTATT-3'(SEQ ID NO:1683)
5'-UUUUGUACAUUACACUAAAUUAUta-3'(SEQ ID NO:981)
3'-UAAAAACAUGUAAUGUGAUUUAAUAAU-5'(SEQ ID NO:278)
KRAS-918靶:5'-ATTTTTGTACATTACACTAAATTATTA-3'(SEQ ID NO:1684)
5'-UUUGUACAUUACACUAAAUUAUUag-3'(SEQ ID NO:982)
3'-AAAAACAUGUAAUGUGAUUUAAUAAUC-5'(SEQ ID NO:279)
KRAS-919靶:5'-TTTTTGTACATTACACTAAATTATTAG-3'(SEQ ID NO:1685)
5'-UUGUACAUUACACUAAAUUAUUAgc-3'(SEQ ID NO:983)
3'-AAAACAUGUAAUGUGAUUUAAUAAUCG-5'(SEQ ID NO:280)
KRAS-920靶:5'-TTTTGTACATTACACTAAATTATTAGC-3'(SEQ ID NO:1686)
5'-CUAAAUUAUUAGCAUUUGUUUUAgc-3'(SEQ ID NO:984)
3'-GUGAUUUAAUAAUCGUAAACAAAAUCG-5'(SEQ ID NO:281)
KRAS-932靶:5'-CACTAAATTATTAGCATTTGTTTTAGC-3'(SEQ ID NO:1687)
5'-AAAUUAUUAGCAUUUGUUUUAGCat-3'(SEQ ID NO:985)
3'-GAUUUAAUAAUCGUAAACAAAAUCGUA-5'(SEQ ID NO:282)
KRAS-934靶:5'-CTAAATTATTAGCATTTGTTTTAGCAT-3'(SEQ ID NO:1688)
5'-AAUUAUUAGCAUUUGUUUUAGCAtt-3'(SEQ ID NO:986)
3'-AUUUAAUAAUCGUAAACAAAAUCGUAA-5'(SEQ ID NO:283)
KRAS-935靶:5'-TAAATTATTAGCATTTGTTTTAGCATT-3'(SEQ ID NO:1689)
5'-UUAGCAUUUGUUUUAGCAUUACCta-3'(SEQ ID NO:987)
3'-AUAAUCGUAAACAAAAUCGUAAUGGAU-5'(SEQ ID NO:284)
KRAS-940靶:5'-TATTAGCATTTGTTTTAGCATTACCTA-3'(SEQ ID NO:1690)
5'-UUUGUUUUAGCAUUACCUAAUUUtt-3'(SEQ ID NO:988)
3'-GUAAACAAAAUCGUAAUGGAUUAAAAA-5'(SEQ ID NO:285)
KRAS-946靶:5'-CATTTGTTTTAGCATTACCTAATTTTT-3'(SEQ ID NO:1691)
5'-UUGUUUUAGCAUUACCUAAUUUUtt-3'(SEQ ID NO:989)
3'-UAAACAAAAUCGUAAUGGAUUAAAAAA-5'(SEQ ID NO:286)
KRAS-947靶:5'-ATTTGTTTTAGCATTACCTAATTTTTT-3'(SEQ ID NO:1692)
5'-GUUUUAGCAUUACCUAAUUUUUUtc-3'(SEQ ID NO:990)
3'-AACAAAAUCGUAAUGGAUUAAAAAAAG-5'(SEQ ID NO:287)
KRAS-949靶:5'-TTGTTTTAGCATTACCTAATTTTTTTC-3'(SEQ ID NO:1693)
5'-UUUUAGCAUUACCUAAUUUUUUUcc-3'(SEQ ID NO:991)
3'-ACAAAAUCGUAAUGGAUUAAAAAAAGG-5'(SEQ ID NO:288)
KRAS-950靶:5'-TGTTTTAGCATTACCTAATTTTTTTCC-3'(SEQ ID NO:1694)
5'-UUUAGCAUUACCUAAUUUUUUUCct-3'(SEQ ID NO:992)
3'-CAAAAUCGUAAUGGAUUAAAAAAAGGA-5'(SEQ ID NO:289)
KRAS-951靶:5'-GTTTTAGCATTACCTAATTTTTTTCCT-3'(SEQ ID NO:1695)
5'-UUAGCAUUACCUAAUUUUUUUCCtg-3'(SEQ ID NO:993)
3'-AAAAUCGUAAUGGAUUAAAAAAAGGAC-5'(SEQ ID NO:290)
KRAS-952靶:5'-TTTTAGCATTACCTAATTTTTTTCCTG-3'(SEQ ID NO:1696)
5'-CUGUUAGCUUUUACCUUAAAUGCtt-3'(SEQ ID NO:994)
3'-CUGACAAUCGAAAAUGGAAUUUACGAA-5'(SEQ ID NO:291)
KRAS-988靶:5'-GACTGTTAGCTTTTACCTTAAATGCTT-3'(SEQ ID NO:1697)
5'-UGUUAGCUUUUACCUUAAAUGCUta-3'(SEQ ID NO:995)
3'-UGACAAUCGAAAAUGGAAUUUACGAAU-5'(SEQ ID NO:292)
KRAS-989靶:5'-ACTGTTAGCTTTTACCTTAAATGCTTA-3'(SEQ ID NO:1698)
5'-CUUUUACCUUAAAUGCUUAUUUUaa-3'(SEQ ID NO:996)
3'-UCGAAAAUGGAAUUUACGAAUAAAAUU-5'(SEQ ID NO:293)
KRAS-995靶:5'-AGCTTTTACCTTAAATGCTTATTTTAA-3'(SEQ ID NO:1699)
5'-UUUUACCUUAAAUGCUUAUUUUAaa-3'(SEQ ID NO:997)
3'-CGAAAAUGGAAUUUACGAAUAAAAUUU-5'(SEQ ID NO:294)
KRAS-996靶:5'-GCTTTTACCTTAAATGCTTATTTTAAA-3'(SEQ ID NO:1700)
5'-UUUACCUUAAAUGCUUAUUUUAAaa-3'(SEQ ID NO:998)
3'-GAAAAUGGAAUUUACGAAUAAAAUUUU-5'(SEQ ID NO:295)
KRAS-997靶:5'-CTTTTACCTTAAATGCTTATTTTAAAA-3'(SEQ ID NO:1701)
5'-UUAAAUGCUUAUUUUAAAAUGACag-3'(SEQ ID NO:999)
3'-GGAAUUUACGAAUAAAAUUUUACUGUC-5'(SEQ ID NO:296)
KRAS-1003靶:5'-CCTTAAATGCTTATTTTAAAATGACAG-3'(SEQ ID NO:1702)
5'-UAAAUGCUUAUUUUAAAAUGACAgt-3'(SEQ ID NO:1000)
3'-GAAUUUACGAAUAAAAUUUUACUGUCA-5'(SEQ ID NO:297)
KRAS-1004靶:5'-CTTAAATGCTTATTTTAAAATGACAGT-3'(SEQ ID NO:1703)
5'-CUUAUUUUAAAAUGACAGUGGAAgt-3'(SEQ ID NO:1001)
3'-ACGAAUAAAAUUUUACUGUCACCUUCA-5'(SEQ ID NO:298)
KRAS-1010靶:5'-TGCTTATTTTAAAATGACAGTGGAAGT-3'(SEQ ID NO:1704)
5'-UAUUUUAAAAUGACAGUGGAAGUtt-3'(SEQ ID NO:1002)
3'-GAAUAAAAUUUUACUGUCACCUUCAAA-5'(SEQ ID NO:299)
KRAS-1012靶:5'-CTTATTTTAAAATGACAGTGGAAGTTT-3'(SEQ ID NO:1705)
5'-GGAAGUUUUUUUUUCCUCUAAGUgc-3'(SEQ ID NO:1003)
3'-CACCUUCAAAAAAAAAGGAGAUUCACG-5'(SEQ ID NO:300)
KRAS-1029靶:5'-GTGGAAGTTTTTTTTTCCTCTAAGTGC-3'(SEQ ID NO:1706)
5'-AAGUUUUUUUUUCCUCUAAGUGCca-3'(SEQ ID NO:1004)
3'-CCUUCAAAAAAAAAGGAGAUUCACGGU-5'(SEQ ID NO:301)
KRAS-1031靶:5'-GGAAGTTTTTTTTTCCTCTAAGTGCCA-3'(SEQ ID NO:1707)
5'-AGUUUUUUUUUCCUCUAAGUGCCag-3'(SEQ ID NO:1005)
3'-CUUCAAAAAAAAAGGAGAUUCACGGUC-5'(SEQ ID NO:302)
KRAS-1032靶:5'-GAAGTTTTTTTTTCCTCTAAGTGCCAG-3'(SEQ ID NO:1708)
5'-UUGGUUUUUGAACUAGCAAUGCCtg-3'(SEQ ID NO:1006)
3'-AAAACCAAAAACUUGAUCGUUACGGAC-5'(SEQ ID NO:303)
KRAS-1070靶:5'-TTTTGGTTTTTGAACTAGCAATGCCTG-3'(SEQ ID NO:1709)
5'-CUGUGAAAAAGAAACUGAAUACCta-3'(SEQ ID NO:1007)
3'-CGGACACUUUUUCUUUGACUUAUGGAU-5'(SEQ ID NO:304)
KRAS-1092靶:5'-GCCTGTGAAAAAGAAACTGAATACCTA-3'(SEQ ID NO:1710)
5'-AAAGAAACUGAAUACCUAAGAUUtc-3'(SEQ ID NO:1008)
3'-UUUUUCUUUGACUUAUGGAUUCUAAAG-5'(SEQ ID NO:305)
KRAS-1099靶:5'-AAAAAGAAACTGAATACCTAAGATTTC-3'(SEQ ID NO:1711)
5'-AAGAAACUGAAUACCUAAGAUUUct-3'(SEQ ID NO:1009)
3'-UUUUCUUUGACUUAUGGAUUCUAAAGA-5'(SEQ ID NO:306)
KRAS-1100靶:5'-AAAAGAAACTGAATACCTAAGATTTCT-3'(SEQ ID NO:1712)
5'-CUGAAUACCUAAGAUUUCUGUCUtg-3'(SEQ ID NO:1010)
3'-UUGACUUAUGGAUUCUAAAGACAGAAC-5'(SEQ ID NO:307)
KRAS-1106靶:5'-AACTGAATACCTAAGATTTCTGTCTTG-3'(SEQ ID NO:1713)
5'-CAGUUGAUUACUUCUUAUUUUUCtt-3'(SEQ ID NO:1011)
3'-ACGUCAACUAAUGAAGAAUAAAAAGAA-5'(SEQ ID NO:308)
KRAS-1147靶:5'-TGCAGTTGATTACTTCTTATTTTTCTT-3'(SEQ ID NO:1714)
5'-AGUUGAUUACUUCUUAUUUUUCUta-3'(SEQ ID NO:1012)
3'-CGUCAACUAAUGAAGAAUAAAAAGAAU-5'(SEQ ID NO:309)
KRAS-1148靶:5'-GCAGTTGATTACTTCTTATTTTTCTTA-3'(SEQ ID NO:1715)
5'-GAUUACUUCUUAUUUUUCUUACCaa-3'(SEQ ID NO:1013)
3'-AACUAAUGAAGAAUAAAAAGAAUGGUU-5'(SEQ ID NO:310)
KRAS-1152靶:5'-TTGATTACTTCTTATTTTTCTTACCAA-3'(SEQ ID NO:1716)
5'-CUUAUUUUUCUUACCAAUUGUGAat-3'(SEQ ID NO:1014)
3'-AAGAAUAAAAAGAAUGGUUAACACUUA-5'(SEQ ID NO:311)
KRAS-1160靶:5'-TTCTTATTTTTCTTACCAATTGTGAAT-3'(SEQ ID NO:1717)
5'-UUAUUUUUCUUACCAAUUGUGAAtg-3'(SEQ ID NO:1015)
3'-AGAAUAAAAAGAAUGGUUAACACUUAC-5'(SEQ ID NO:312)
KRAS-1161靶:5'-TCTTATTTTTCTTACCAATTGTGAATG-3'(SEQ ID NO:1718)
5'-UAUUUUUCUUACCAAUUGUGAAUgt-3'(SEQ ID NO:1016)
3'-GAAUAAAAAGAAUGGUUAACACUUACA-5'(SEQ ID NO:313)
KRAS-1162靶:5'-CTTATTTTTCTTACCAATTGTGAATGT-3'(SEQ ID NO:1719)
5'-GUUGGUGUGAAACAAAUUAAUGAag-3'(SEQ ID NO:1017)
3'-UACAACCACACUUUGUUUAAUUACUUC-5'(SEQ ID NO:314)
KRAS-1185靶:5'-ATGTTGGTGTGAAACAAATTAATGAAG-3'(SEQ ID NO:1720)
5'-GGUGUGAAACAAAUUAAUGAAGCtt-3'(SEQ ID NO:1018)
3'-AACCACACUUUGUUUAAUUACUUCGAA-5'(SEQ ID NO:315)
KRAS-1188靶:5'-TTGGTGTGAAACAAATTAATGAAGCTT-3'(SEQ ID NO:1721)
5'-GUGUGAAACAAAUUAAUGAAGCUtt-3'(SEQ ID NO:1019)
3'-ACCACACUUUGUUUAAUUACUUCGAAA-5'(SEQ ID NO:316)
KRAS-1189靶:5'-TGGTGTGAAACAAATTAATGAAGCTTT-3'(SEQ ID NO:1722)
5'-CAAAUUAAUGAAGCUUUUGAAUCat-3'(SEQ ID NO:1020)
3'-UUGUUUAAUUACUUCGAAAACUUAGUA-5'(SEQ ID NO:317)
KRAS-1197靶:5'-AACAAATTAATGAAGCTTTTGAATCAT-3'(SEQ ID NO:1723)
5'-AAAUUAAUGAAGCUUUUGAAUCAtc-3'(SEQ ID NO:1021)
3'-UGUUUAAUUACUUCGAAAACUUAGUAG-5'(SEQ ID NO:318)
KRAS-1198靶:5'-ACAAATTAATGAAGCTTTTGAATCATC-3'(SEQ ID NO:1724)
5'-UGUGUUUUAUCUAGUCACAUAAAtg-3'(SEQ ID NO:1022)
3'-AGACACAAAAUAGAUCAGUGUAUUUAC-5'(SEQ ID NO:319)
KRAS-1230靶:5'-TCTGTGTTTTATCTAGTCACATAAATG-3'(SEQ ID NO:1725)
5'-GUGUUUUAUCUAGUCACAUAAAUgg-3'(SEQ ID NO:1023)
3'-GACACAAAAUAGAUCAGUGUAUUUACC-5'(SEQ ID NO:320)
KRAS-1231靶:5'-CTGTGTTTTATCTAGTCACATAAATGG-3'(SEQ ID NO:1726)
5'-UUUUAUCUAGUCACAUAAAUGGAtt-3'(SEQ ID NO:1024)
3'-ACAAAAUAGAUCAGUGUAUUUACCUAA-5'(SEQ ID NO:321)
KRAS-1234靶:5'-TGTTTTATCTAGTCACATAAATGGATT-3'(SEQ ID NO:1727)
5'-UUUAUCUAGUCACAUAAAUGGAUta-3'(SEQ ID NO:1025)
3'-CAAAAUAGAUCAGUGUAUUUACCUAAU-5'(SEQ ID NO:322)
KRAS-1235靶:5'-GTTTTATCTAGTCACATAAATGGATTA-3'(SEQ ID NO:1728)
5'-CUAGUCACAUAAAUGGAUUAAUUac-3'(SEQ ID NO:1026)
3'-UAGAUCAGUGUAUUUACCUAAUUAAUG-5'(SEQ ID NO:323)
KRAS-1240靶:5'-ATCTAGTCACATAAATGGATTAATTAC-3'(SEQ ID NO:1729)
5'-UAGUCACAUAAAUGGAUUAAUUAct-3'(SEQ ID NO:1027)
3'-AGAUCAGUGUAUUUACCUAAUUAAUGA-5'(SEQ ID NO:324)
KRAS-1241靶:5'-TCTAGTCACATAAATGGATTAATTACT-3'(SEQ ID NO:1730)
5'-UAAAUGGAUUAAUUACUAAUUUCag-3'(SEQ ID NO:1028)
3'-GUAUUUACCUAAUUAAUGAUUAAAGUC-5'(SEQ ID NO:325)
KRAS-1249靶:5'-CATAAATGGATTAATTACTAATTTCAG-3'(SEQ ID NO:1731)
5'-AAAUGGAUUAAUUACUAAUUUCAgt-3'(SEQ ID NO:1029)
3'-UAUUUACCUAAUUAAUGAUUAAAGUCA-5'(SEQ ID NO:326)
KRAS-1250靶:5'-ATAAATGGATTAATTACTAATTTCAGT-3'(SEQ ID NO:1732)
5'-GAUUAAUUACUAAUUUCAGUUGAga-3'(SEQ ID NO:1030)
3'-ACCUAAUUAAUGAUUAAAGUCAACUCU-5'(SEQ ID NO:327)
KRAS-1255靶:5'-TGGATTAATTACTAATTTCAGTTGAGA-3'(SEQ ID NO:1733)
5'-UUAAUUACUAAUUUCAGUUGAGAcc-3'(SEQ ID NO:1031)
3'-CUAAUUAAUGAUUAAAGUCAACUCUGG-5'(SEQ ID NO:328)
KRAS-1257靶:5'-GATTAATTACTAATTTCAGTTGAGACC-3'(SEQ ID NO:1734)
5'-UAAUUACUAAUUUCAGUUGAGACct-3'(SEQ ID NO:1032)
3'-UAAUUAAUGAUUAAAGUCAACUCUGGA-5'(SEQ ID NO:329)
KRAS-1258靶:5'-ATTAATTACTAATTTCAGTTGAGACCT-3'(SEQ ID NO:1735)
5'-AAUUACUAAUUUCAGUUGAGACCtt-3'(SEQ ID NO:1033)
3'-AAUUAAUGAUUAAAGUCAACUCUGGAA-5'(SEQ ID NO:330)
KRAS-1259靶:5'-TTAATTACTAATTTCAGTTGAGACCTT-3'(SEQ ID NO:1736)
5'-AUUGGUUUUUACUGAAACAUUGAgg-3'(SEQ ID NO:1034)
3'-AUUAACCAAAAAUGACUUUGUAACUCC-5'(SEQ ID NO:331)
KRAS-1287靶:5'-TAATTGGTTTTTACTGAAACATTGAGG-3'(SEQ ID NO:1737)
5'-GUUUUUACUGAAACAUUGAGGGAac-3'(SEQ ID NO:1035)
3'-ACCAAAAAUGACUUUGUAACUCCCUUG-5'(SEQ ID NO:332)
KRAS-1291靶:5'-TGGTTTTTACTGAAACATTGAGGGAAC-3'(SEQ ID NO:1738)
5'-UUUUUACUGAAACAUUGAGGGAAca-3'(SEQ ID NO:1036)
3'-CCAAAAAUGACUUUGUAACUCCCUUGU-5'(SEQ ID NO:333)
KRAS-1292靶:5'-GGTTTTTACTGAAACATTGAGGGAACA-3'(SEQ ID NO:1739)
5'-UGAGGGAACACAAAUUUAUGGGCtt-3'(SEQ ID NO:1037)
3'-UAACUCCCUUGUGUUUAAAUACCCGAA-5'(SEQ ID NO:334)
KRAS-1307靶:5'-ATTGAGGGAACACAAATTTATGGGCTT-3'(SEQ ID NO:1740)
5'-GAGGGAACACAAAUUUAUGGGCUtc-3'(SEQ ID NO:1038)
3'-AACUCCCUUGUGUUUAAAUACCCGAAG-5'(SEQ ID NO:335)
KRAS-1308靶:5'-TTGAGGGAACACAAATTTATGGGCTTC-3'(SEQ ID NO:1741)
5'-AUGAAUGUAAAGUUACACUGUUCac-3'(SEQ ID NO:1039)
3'-ACUACUUACAUUUCAAUGUGACAAGUG-5'(SEQ ID NO:336)
KRAS-1381靶:5'-TGATGAATGTAAAGTTACACTGTTCAC-3'(SEQ ID NO:1742)
5'-UGAAUGUAAAGUUACACUGUUCAca-3'(SEQ ID NO:1040)
3'-CUACUUACAUUUCAAUGUGACAAGUGU-5'(SEQ ID NO:337)
KRAS-1382靶:5'-GATGAATGTAAAGTTACACTGTTCACA-3'(SEQ ID NO:1743)
5'-AAAAUAUUAUAUUUUUUCUAUAAaa-3'(SEQ ID NO:1041)
3'-GGUUUUAUAAUAUAAAAAAGAUAUUUU-5'(SEQ ID NO:338)
KRAS-1454靶:5'-CCAAAATATTATATTTTTTCTATAAAA-3'(SEQ ID NO:1744)
5'-AAAUAUUAUAUUUUUUCUAUAAAaa-3'(SEQ ID NO:1042)
3'-GUUUUAUAAUAUAAAAAAGAUAUUUUU-5'(SEQ ID NO:339)
KRAS-1455靶:5'-CAAAATATTATATTTTTTCTATAAAAA-3'(SEQ ID NO:1745)
5'-AAUAUUAUAUUUUUUCUAUAAAAag-3'(SEQ ID NO:1043)
3'-UUUUAUAAUAUAAAAAAGAUAUUUUUC-5'(SEQ ID NO:340)
KRAS-1456靶:5'-AAAATATTATATTTTTTCTATAAAAAG-3'(SEQ ID NO:1746)
5'-AUAUUAUAUUUUUUCUAUAAAAAga-3'(SEQ ID NO:1044)
3'-UUUAUAAUAUAAAAAAGAUAUUUUUCU-5'(SEQ ID NO:341)
KRAS-1457靶:5'-AAATATTATATTTTTTCTATAAAAAGA-3'(SEQ ID NO:1747)
5'-AUUAUAUUUUUUCUAUAAAAAGAaa-3'(SEQ ID NO:1045)
3'-UAUAAUAUAAAAAAGAUAUUUUUCUUU-5'(SEQ ID NO:342)
KRAS-1459靶:5'-ATATTATATTTTTTCTATAAAAAGAAA-3'(SEQ ID NO:1748)
5'-UUAUAUUUUUUCUAUAAAAAGAAaa-3'(SEQ ID NO:1046)
3'-AUAAUAUAAAAAAGAUAUUUUUCUUUU-5'(SEQ ID NO:343)
KRAS-1460靶:5'-TATTATATTTTTTCTATAAAAAGAAAA-3'(SEQ ID NO:1749)
5'-UAUAUUUUUUCUAUAAAAAGAAAaa-3'(SEQ ID NO:1047)
3'-UAAUAUAAAAAAGAUAUUUUUCUUUUU-5'(SEQ ID NO:344)
KRAS-1461靶:5'-ATTATATTTTTTCTATAAAAAGAAAAA-3'(SEQ ID NO:1750)
5'-AUAUUUUUUCUAUAAAAAGAAAAaa-3'(SEQ ID NO:1048)
3'-AAUAUAAAAAAGAUAUUUUUCUUUUUU-5'(SEQ ID NO:345)
KRAS-1462靶:5'-TTATATTTTTTCTATAAAAAGAAAAAA-3'(SEQ ID NO:1751)
5'-UAUUUUUUCUAUAAAAAGAAAAAaa-3'(SEQ ID NO:1049)
3'-AUAUAAAAAAGAUAUUUUUCUUUUUUU-5'(SEQ ID NO:346)
KRAS-1463靶:5'-TATATTTTTTCTATAAAAAGAAAAAAA-3'(SEQ ID NO:1752)
5'-AUUUUUUCUAUAAAAAGAAAAAAat-3'(SEQ ID NO:1050)
3'-UAUAAAAAAGAUAUUUUUCUUUUUUUA-5'(SEQ ID NO:347)
KRAS-1464靶:5'-ATATTTTTTCTATAAAAAGAAAAAAAT-3'(SEQ ID NO:1753)
5'-UUUUUUCUAUAAAAAGAAAAAAAtg-3'(SEQ ID NO:1051)
3'-AUAAAAAAGAUAUUUUUCUUUUUUUAC-5'(SEQ ID NO:348)
KRAS-1465靶:5'-TATTTTTTCTATAAAAAGAAAAAAATG-3'(SEQ ID NO:1754)
5'-UUUUUCUAUAAAAAGAAAAAAAUgg-3'(SEQ ID NO:1052)
3'-UAAAAAAGAUAUUUUUCUUUUUUUACC-5'(SEQ ID NO:349)
KRAS-1466靶:5'-ATTTTTTCTATAAAAAGAAAAAAATGG-3'(SEQ ID NO:1755)
5'-CUAUAAAAAGAAAAAAAUGGAAAaa-3'(SEQ ID NO:1053)
3'-AAGAUAUUUUUCUUUUUUUACCUUUUU-5'(SEQ ID NO:350)
KRAS-1471靶:5'-TTCTATAAAAAGAAAAAAATGGAAAAA-3'(SEQ ID NO:1756)
5'-UAUAAAAAGAAAAAAAUGGAAAAaa-3'(SEQ ID NO:1054)
3'-AGAUAUUUUUCUUUUUUUACCUUUUUU-5'(SEQ ID NO:351)
KRAS-1472靶:5'-TCTATAAAAAGAAAAAAATGGAAAAAA-3'(SEQ ID NO:1757)
5'-UAAAAAGAAAAAAAUGGAAAAAAat-3'(SEQ ID NO:1055)
3'-AUAUUUUUCUUUUUUUACCUUUUUUUA-5'(SEQ ID NO:352)
KRAS-1474靶:5'-TATAAAAAGAAAAAAATGGAAAAAAAT-3'(SEQ ID NO:1758)
5'-AAAAAGAAAAAAAUGGAAAAAAAtt-3'(SEQ ID NO:1056)
3'-UAUUUUUCUUUUUUUACCUUUUUUUAA-5'(SEQ ID NO:353)
KRAS-1475靶:5'-ATAAAAAGAAAAAAATGGAAAAAAATT-3'(SEQ ID NO:1759)
5'-AAAAGAAAAAAAUGGAAAAAAAUta-3'(SEQ ID NO:1057)
3'-AUUUUUCUUUUUUUACCUUUUUUUAAU-5'(SEQ ID NO:354)
KRAS-1476靶:5'-TAAAAAGAAAAAAATGGAAAAAAATTA-3'(SEQ ID NO:1760)
5'-AAAGAAAAAAAUGGAAAAAAAUUac-3'(SEQ ID NO:1058)
3'-UUUUUCUUUUUUUACCUUUUUUUAAUG-5'(SEQ ID NO:355)
KRAS-1477靶:5'-AAAAAGAAAAAAATGGAAAAAAATTAC-3'(SEQ ID NO:1761)
5'-AAGAAAAAAAUGGAAAAAAAUUAca-3'(SEQ ID NO:1059)
3'-UUUUCUUUUUUUACCUUUUUUUAAUGU-5'(SEQ ID NO:356)
KRAS-1478靶:5'-AAAAGAAAAAAATGGAAAAAAATTACA-3'(SEQ ID NO:1762)
5'-AGAAAAAAAUGGAAAAAAAUUACaa-3'(SEQ ID NO:1060)
3'-UUUCUUUUUUUACCUUUUUUUAAUGUU-5'(SEQ ID NO:357)
KRAS-1479靶:5'-AAAGAAAAAAATGGAAAAAAATTACAA-3'(SEQ ID NO:1763)
5'-GAAAAAAAUGGAAAAAAAUUACAag-3'(SEQ ID NO:1061)
3'-UUCUUUUUUUACCUUUUUUUAAUGUUC-5'(SEQ ID NO:358)
KRAS-1480靶:5'-AAGAAAAAAATGGAAAAAAATTACAAG-3'(SEQ ID NO:1764)
5'-AAAAUGGAAAAAAAUUACAAGGCaa-3'(SEQ ID NO:1062)
3'-UUUUUUACCUUUUUUUAAUGUUCCGUU-5'(SEQ ID NO:359)
KRAS-1484靶:5'-AAAAAATGGAAAAAAATTACAAGGCAA-3'(SEQ ID NO:1765)
5'-AAAUGGAAAAAAAUUACAAGGCAat-3'(SEQ ID NO:1063)
3'-UUUUUACCUUUUUUUAAUGUUCCGUUA-5'(SEQ ID NO:360)
KRAS-1485靶:5'-AAAAATGGAAAAAAATTACAAGGCAAT-3'(SEQ ID NO:1766)
5'-GAAAAAAAUUACAAGGCAAUGGAaa-3'(SEQ ID NO:1064)
3'-ACCUUUUUUUAAUGUUCCGUUACCUUU-5'(SEQ ID NO:361)
KRAS-1490靶:5'-TGGAAAAAAATTACAAGGCAATGGAAA-3'(SEQ ID NO:1767)
5'-AAAAAAAUUACAAGGCAAUGGAAac-3'(SEQ ID NO:1065)
3'-CCUUUUUUUAAUGUUCCGUUACCUUUG-5'(SEQ ID NO:362)
KRAS-1491靶:5'-GGAAAAAAATTACAAGGCAATGGAAAC-3'(SEQ ID NO:1768)
5'-AAAAAAUUACAAGGCAAUGGAAAct-3'(SEQ ID NO:1066)
3'-CUUUUUUUAAUGUUCCGUUACCUUUGA-5'(SEQ ID NO:363)
KRAS-1492靶:5'-GAAAAAAATTACAAGGCAATGGAAACT-3'(SEQ ID NO:1769)
5'-CAUUUCCUUUUCACAUUAGAUAAat-3'(SEQ ID NO:1067)
3'-CGGUAAAGGAAAAGUGUAAUCUAUUUA-5'(SEQ ID NO:364)
KRAS-1527靶:5'-GCCATTTCCTTTTCACATTAGATAAAT-3'(SEQ ID NO:1770)
5'-CUUUUCACAUUAGAUAAAUUACUat-3'(SEQ ID NO:1068)
3'-AGGAAAAGUGUAAUCUAUUUAAUGAUA-5'(SEQ ID NO:365)
KRAS-1533靶:5'-TCCTTTTCACATTAGATAAATTACTAT-3'(SEQ ID NO:1771)
5'-CAUUAGAUAAAUUACUAUAAAGAct-3'(SEQ ID NO:1069)
3'-GUGUAAUCUAUUUAAUGAUAUUUCUGA-5'(SEQ ID NO:366)
KRAS-1540靶:5'-CACATTAGATAAATTACTATAAAGACT-3'(SEQ ID NO:1772)
5'-AUUAGAUAAAUUACUAUAAAGACtc-3'(SEQ ID NO:1070)
3'-UGUAAUCUAUUUAAUGAUAUUUCUGAG-5'(SEQ ID NO:367)
KRAS-1541靶:5'-ACATTAGATAAATTACTATAAAGACTC-3'(SEQ ID NO:1773)
5'-UUAGAUAAAUUACUAUAAAGACUcc-3'(SEQ ID NO:1071)
3'-GUAAUCUAUUUAAUGAUAUUUCUGAGG-5'(SEQ ID NO:368)
KRAS-1542靶:5'-CATTAGATAAATTACTATAAAGACTCC-3'(SEQ ID NO:1774)
5'-UAUGAAAUGGGGAUUAUUAUAGCaa-3'(SEQ ID NO:1072)
3'-UCAUACUUUACCCCUAAUAAUAUCGUU-5'(SEQ ID NO:369)
KRAS-1597靶:5'-AGTATGAAATGGGGATTATTATAGCAA-3'(SEQ ID NO:1775)
5'-GGGAUUAUUAUAGCAACCAUUUUgg-3'(SEQ ID NO:1073)
3'-ACCCCUAAUAAUAUCGUUGGUAAAACC-5'(SEQ ID NO:370)
KRAS-1606靶:5'-TGGGGATTATTATAGCAACCATTTTGG-3'(SEQ ID NO:1776)
5'-CUAUAUUUACAUGCUACUAAAUUtt-3'(SEQ ID NO:1074)
3'-CCGAUAUAAAUGUACGAUGAUUUAAAA-5'(SEQ ID NO:371)
KRAS-1633靶:5'-GGCTATATTTACATGCTACTAAATTTT-3'(SEQ ID NO:1777)
5'-UAUAUUUACAUGCUACUAAAUUUtt-3'(SEQ ID NO:1075)
3'-CGAUAUAAAUGUACGAUGAUUUAAAAA-5'(SEQ ID NO:372)
KRAS-1634靶:5'-GCTATATTTACATGCTACTAAATTTTT-3'(SEQ ID NO:1778)
5'-AUAUUUACAUGCUACUAAAUUUUta-3'(SEQ ID NO:1076)
3'-GAUAUAAAUGUACGAUGAUUUAAAAAU-5'(SEQ ID NO:373)
KRAS-1635靶:5'-CTATATTTACATGCTACTAAATTTTTA-3'(SEQ ID NO:1779)
5'-UAUUUACAUGCUACUAAAUUUUUat-3'(SEQ ID NO:1077)
3'-AUAUAAAUGUACGAUGAUUUAAAAAUA-5'(SEQ ID NO:374)
KRAS-1636靶:5'-TATATTTACATGCTACTAAATTTTTAT-3'(SEQ ID NO:1780)
5'-AUUUACAUGCUACUAAAUUUUUAta-3'(SEQ ID NO:1078)
3'-UAUAAAUGUACGAUGAUUUAAAAAUAU-5'(SEQ ID NO:375)
KRAS-1637靶:5'-ATATTTACATGCTACTAAATTTTTATA-3'(SEQ ID NO:1781)
5'-CAUGCUACUAAAUUUUUAUAAUAat-3'(SEQ ID NO:1079)
3'-AUGUACGAUGAUUUAAAAAUAUUAUUA-5'(SEQ ID NO:376)
KRAS-1642靶:5'-TACATGCTACTAAATTTTTATAATAAT-3'(SEQ ID NO:1782)
5'-CUAAAUUUUUAUAAUAAUUGAAAag-3'(SEQ ID NO:1080)
3'-AUGAUUUAAAAAUAUUAUUAACUUUUC-5'(SEQ ID NO:377)
KRAS-1649靶:5'-TACTAAATTTTTATAATAATTGAAAAG-3'(SEQ ID NO:1783)
5'-UAAAUUUUUAUAAUAAUUGAAAAga-3'(SEQ ID NO:1081)
3'-UGAUUUAAAAAUAUUAUUAACUUUUCU-5'(SEQ ID NO:378)
KRAS-1650靶:5'-ACTAAATTTTTATAATAATTGAAAAGA-3'(SEQ ID NO:1784)
5'-AAUUUUUAUAAUAAUUGAAAAGAtt-3'(SEQ ID NO:1082)
3'-AUUUAAAAAUAUUAUUAACUUUUCUAA-5'(SEQ ID NO:379)
KRAS-1652靶:5'-TAAATTTTTATAATAATTGAAAAGATT-3'(SEQ ID NO:1785)
5'-AUUUUUAUAAUAAUUGAAAAGAUtt-3'(SEQ ID NO:1083)
3'-UUUAAAAAUAUUAUUAACUUUUCUAAA-5'(SEQ ID NO:380)
KRAS-1653靶:5'-AAATTTTTATAATAATTGAAAAGATTT-3'(SEQ ID NO:1786)
5'-UUUUUAUAAUAAUUGAAAAGAUUtt-3'(SEQ ID NO:1084)
3'-UUAAAAAUAUUAUUAACUUUUCUAAAA-5'(SEQ ID NO:381)
KRAS-1654靶:5'-AATTTTTATAATAATTGAAAAGATTTT-3'(SEQ ID NO:1787)
5'-UUUUAUAAUAAUUGAAAAGAUUUta-3'(SEQ ID NO:1085)
3'-UAAAAAUAUUAUUAACUUUUCUAAAAU-5'(SEQ ID NO:382)
KRAS-1655靶:5'-ATTTTTATAATAATTGAAAAGATTTTA-3'(SEQ ID NO:1788)
5'-UUUAUAAUAAUUGAAAAGAUUUUaa-3'(SEQ ID NO:1086)
3'-AAAAAUAUUAUUAACUUUUCUAAAAUU-5'(SEQ ID NO:383)
KRAS-1656靶:5'-TTTTTATAATAATTGAAAAGATTTTAA-3'(SEQ ID NO:1789)
5'-UUAUAAUAAUUGAAAAGAUUUUAac-3'(SEQ ID NO:1087)
3'-AAAAUAUUAUUAACUUUUCUAAAAUUG-5'(SEQ ID NO:384)
KRAS-1657靶:5'-TTTTATAATAATTGAAAAGATTTTAAC-3'(SEQ ID NO:1790)
5'-UAUAAUAAUUGAAAAGAUUUUAAca-3'(SEQ ID NO:1088)
3'-AAAUAUUAUUAACUUUUCUAAAAUUGU-5'(SEQ ID NO:385)
KRAS-1658靶:5'-TTTATAATAATTGAAAAGATTTTAACA-3'(SEQ ID NO:1791)
5'-AUAAUAAUUGAAAAGAUUUUAACaa-3'(SEQ ID NO:1089)
3'-AAUAUUAUUAACUUUUCUAAAAUUGUU-5'(SEQ ID NO:386)
KRAS-1659靶:5'-TTATAATAATTGAAAAGATTTTAACAA-3'(SEQ ID NO:1792)
5'-UAAUAAUUGAAAAGAUUUUAACAag-3'(SEQ ID NO:1090)
3'-AUAUUAUUAACUUUUCUAAAAUUGUUC-5'(SEQ ID NO:387)
KRAS-1660靶:5'-TATAATAATTGAAAAGATTTTAACAAG-3'(SEQ ID NO:1793)
5'-AAUUGAAAAGAUUUUAACAAGUAta-3'(SEQ ID NO:1091)
3'-UAUUAACUUUUCUAAAAUUGUUCAUAU-5'(SEQ ID NO:388)
KRAS-1664靶:5'-ATAATTGAAAAGATTTTAACAAGTATA-3'(SEQ ID NO:1794)
5'-AUUGAAAAGAUUUUAACAAGUAUaa-3'(SEQ ID NO:1092)
3'-AUUAACUUUUCUAAAAUUGUUCAUAUU-5'(SEQ ID NO:389)
KRAS-1665靶:5'-TAATTGAAAAGATTTTAACAAGTATAA-3'(SEQ ID NO:1795)
5'-UGAAAAGAUUUUAACAAGUAUAAaa-3'(SEQ ID NO:1093)
3'-UAACUUUUCUAAAAUUGUUCAUAUUUU-5'(SEQ ID NO:390)
KRAS-1667靶:5'-ATTGAAAAGATTTTAACAAGTATAAAA-3'(SEQ ID NO:1796)
5'-GAAAAGAUUUUAACAAGUAUAAAaa-3'(SEQ ID NO:1094)
3'-AACUUUUCUAAAAUUGUUCAUAUUUUU-5'(SEQ ID NO:391)
KRAS-1668靶:5'-TTGAAAAGATTTTAACAAGTATAAAAA-3'(SEQ ID NO:1797)
5'-AAAAGAUUUUAACAAGUAUAAAAaa-3'(SEQ ID NO:1095)
3'-ACUUUUCUAAAAUUGUUCAUAUUUUUU-5'(SEQ ID NO:392)
KRAS-1669靶:5'-TGAAAAGATTTTAACAAGTATAAAAAA-3'(SEQ ID NO:1798)
5'-AAAGAUUUUAACAAGUAUAAAAAat-3'(SEQ ID NO:1096)
3'-CUUUUCUAAAAUUGUUCAUAUUUUUUA-5'(SEQ ID NO:393)
KRAS-1670靶:5'-GAAAAGATTTTAACAAGTATAAAAAAT-3'(SEQ ID NO:1799)
5'-AAGAUUUUAACAAGUAUAAAAAAtt-3'(SEQ ID NO:1097)
3'-UUUUCUAAAAUUGUUCAUAUUUUUUAA-5'(SEQ ID NO:394)
KRAS-1671靶:5'-AAAAGATTTTAACAAGTATAAAAAATT-3'(SEQ ID NO:1800)
5'-AGAUUUUAACAAGUAUAAAAAAUtc-3'(SEQ ID NO:1098)
3'-UUUCUAAAAUUGUUCAUAUUUUUUAAG-5'(SEQ ID NO:395)
KRAS-1672靶:5'-AAAGATTTTAACAAGTATAAAAAATTC-3'(SEQ ID NO:1801)
5'-GAUUUUAACAAGUAUAAAAAAUUct-3'(SEQ ID NO:1099)
3'-UUCUAAAAUUGUUCAUAUUUUUUAAGA-5'(SEQ ID NO:396)
KRAS-1673靶:5'-AAGATTTTAACAAGTATAAAAAATTCT-3'(SEQ ID NO:1802)
5'-AUUUUAACAAGUAUAAAAAAUUCtc-3'(SEQ ID NO:1100)
3'-UCUAAAAUUGUUCAUAUUUUUUAAGAG-5'(SEQ ID NO:397)
KRAS-1674靶:5'-AGATTTTAACAAGTATAAAAAATTCTC-3'(SEQ ID NO:1803)
5'-UUUUAACAAGUAUAAAAAAUUCUca-3'(SEQ ID NO:1101)
3'-CUAAAAUUGUUCAUAUUUUUUAAGAGU-5'(SEQ ID NO:398)
KRAS-1675靶:5'-GATTTTAACAAGTATAAAAAATTCTCA-3'(SEQ ID NO:1804)
5'-AAGUAUAAAAAAUUCUCAUAGGAat-3'(SEQ ID NO:1102)
3'-UGUUCAUAUUUUUUAAGAGUAUCCUUA-5'(SEQ ID NO:399)
KRAS-1682靶:5'-ACAAGTATAAAAAATTCTCATAGGAAT-3'(SEQ ID NO:1805)
5'-AGUAUAAAAAAUUCUCAUAGGAAtt-3'(SEQ ID NO:1103)
3'-GUUCAUAUUUUUUAAGAGUAUCCUUAA-5'(SEQ ID NO:400)
KRAS-1683靶:5'-CAAGTATAAAAAATTCTCATAGGAATT-3'(SEQ ID NO:1806)
5'-GUAUAAAAAAUUCUCAUAGGAAUta-3'(SEQ ID NO:1104)
3'-UUCAUAUUUUUUAAGAGUAUCCUUAAU-5'(SEQ ID NO:401)
KRAS-1684靶:5'-AAGTATAAAAAATTCTCATAGGAATTA-3'(SEQ ID NO:1807)
5'-UAUAAAAAAUUCUCAUAGGAAUUaa-3'(SEQ ID NO:1105)
3'-UCAUAUUUUUUAAGAGUAUCCUUAAUU-5'(SEQ ID NO:402)
KRAS-1685靶:5'-AGTATAAAAAATTCTCATAGGAATTAA-3'(SEQ ID NO:1808)
5'-AUAAAAAAUUCUCAUAGGAAUUAaa-3'(SEQ ID NO:1106)
3'-CAUAUUUUUUAAGAGUAUCCUUAAUUU-5'(SEQ ID NO:403)
KRAS-1686靶:5'-GTATAAAAAATTCTCATAGGAATTAAA-3'(SEQ ID NO:1809)
5'-UAAAAAAUUCUCAUAGGAAUUAAat-3'(SEQ ID NO:1107)
3'-AUAUUUUUUAAGAGUAUCCUUAAUUUA-5'(SEQ ID NO:404)
KRAS-1687靶:5'-TATAAAAAATTCTCATAGGAATTAAAT-3'(SEQ ID NO:1810)
5'-AAAAAAUUCUCAUAGGAAUUAAAtg-3'(SEQ ID NO:1108)
3'-UAUUUUUUAAGAGUAUCCUUAAUUUAC-5'(SEQ ID NO:405)
KRAS-1688靶:5'-ATAAAAAATTCTCATAGGAATTAAATG-3'(SEQ ID NO:1811)
5'-AAAAAUUCUCAUAGGAAUUAAAUgt-3'(SEQ ID NO:1109)
3'-AUUUUUUAAGAGUAUCCUUAAUUUACA-5'(SEQ ID NO:406)
KRAS-1689靶:5'-TAAAAAATTCTCATAGGAATTAAATGT-3'(SEQ ID NO:1812)
5'-AAAUUCUCAUAGGAAUUAAAUGUag-3'(SEQ ID NO:1110)
3'-UUUUUAAGAGUAUCCUUAAUUUACAUC-5'(SEQ ID NO:407)
KRAS-1691靶:5'-AAAAATTCTCATAGGAATTAAATGTAG-3'(SEQ ID NO:1813)
5'-AAUUCUCAUAGGAAUUAAAUGUAgt-3'(SEQ ID NO:1111)
3'-UUUUAAGAGUAUCCUUAAUUUACAUCA-5'(SEQ ID NO:408)
KRAS-1692靶:5'-AAAATTCTCATAGGAATTAAATGTAGT-3'(SEQ ID NO:1814)
5'-CUUUCAUAGUAUAACUUUAAAUCtt-3'(SEQ ID NO:1112)
3'-GAGAAAGUAUCAUAUUGAAAUUUAGAA-5'(SEQ ID NO:409)
KRAS-1736靶:5'-CTCTTTCATAGTATAACTTTAAATCTT-3'(SEQ ID NO:1815)
5'-AUAGUAUAACUUUAAAUCUUUUCtt-3'(SEQ ID NO:1113)
3'-AGUAUCAUAUUGAAAUUUAGAAAAGAA-5'(SEQ ID NO:410)
KRAS-1741靶:5'-TCATAGTATAACTTTAAATCTTTTCTT-3'(SEQ ID NO:1816)
5'-UAGUAUAACUUUAAAUCUUUUCUtc-3'(SEQ ID NO:1114)
3'-GUAUCAUAUUGAAAUUUAGAAAAGAAG-5'(SEQ ID NO:411)
KRAS-1742靶:5'-CATAGTATAACTTTAAATCTTTTCTTC-3'(SEQ ID NO:1817)
5'-UAAAUCUUUUCUUCAACUUGAGUct-3'(SEQ ID NO:1115)
3'-AAAUUUAGAAAAGAAGUUGAACUCAGA-5'(SEQ ID NO:412)
KRAS-1753靶:5'-TTTAAATCTTTTCTTCAACTTGAGTCT-3'(SEQ ID NO:1818)
5'-AAAUCUUUUCUUCAACUUGAGUCtt-3'(SEQ ID NO:1116)
3'-AAUUUAGAAAAGAAGUUGAACUCAGAA-5'(SEQ ID NO:413)
KRAS-1754靶:5'-TTAAATCTTTTCTTCAACTTGAGTCTT-3'(SEQ ID NO:1819)
5'-CUUGAGUCUUUGAAGAUAGUUUUaa-3'(SEQ ID NO:1117)
3'-UUGAACUCAGAAACUUCUAUCAAAAUU-5'(SEQ ID NO:414)
KRAS-1769靶:5'-AACTTGAGTCTTTGAAGATAGTTTTAA-3'(SEQ ID NO:1820)
5'-UGAGUCUUUGAAGAUAGUUUUAAtt-3'(SEQ ID NO:1118)
3'-GAACUCAGAAACUUCUAUCAAAAUUAA-5'(SEQ ID NO:415)
KRAS-1771靶:5'-CTTGAGTCTTTGAAGATAGTTTTAATT-3'(SEQ ID NO:1821)
5'-GAGUCUUUGAAGAUAGUUUUAAUtc-3'(SEQ ID NO:1119)
3'-AACUCAGAAACUUCUAUCAAAAUUAAG-5'(SEQ ID NO:416)
KRAS-1772靶:5'-TTGAGTCTTTGAAGATAGTTTTAATTC-3'(SEQ ID NO:1822)
5'-GAUAGUUUUAAUUCUGCUUGUGAca-3'(SEQ ID NO:1120)
3'-UUCUAUCAAAAUUAAGACGAACACUGU-5'(SEQ ID NO:417)
KRAS-1783靶:5'-AAGATAGTTTTAATTCTGCTTGTGACA-3'(SEQ ID NO:1823)
5'-AUAGUUUUAAUUCUGCUUGUGACat-3'(SEQ ID NO:1121)
3'-UCUAUCAAAAUUAAGACGAACACUGUA-5'(SEQ ID NO:418)
KRAS-1784靶:5'-AGATAGTTTTAATTCTGCTTGTGACAT-3'(SEQ ID NO:1824)
5'-UAGUUUUAAUUCUGCUUGUGACAtt-3'(SEQ ID NO:1122)
3'-CUAUCAAAAUUAAGACGAACACUGUAA-5'(SEQ ID NO:419)
KRAS-1785靶:5'-GATAGTTTTAATTCTGCTTGTGACATT-3'(SEQ ID NO:1825)
5'-CUUGUGACAUUAAAAGAUUAUUUgg-3'(SEQ ID NO:1123)
3'-ACGAACACUGUAAUUUUCUAAUAAACC-5'(SEQ ID NO:420)
KRAS-1799靶:5'-TGCTTGTGACATTAAAAGATTATTTGG-3'(SEQ ID NO:1826)
5'-CAUUGCUUUUGUUUCUUAAGAAAac-3'(SEQ ID NO:1124)
3'-UCGUAACGAAAACAAAGAAUUCUUUUG-5'(SEQ ID NO:421)
KRAS-2047靶:5'-AGCATTGCTTTTGTTTCTTAAGAAAAC-3'(SEQ ID NO:1827)
5'-AUUGCUUUUGUUUCUUAAGAAAAca-3'(SEQ ID NO:1125)
3'-CGUAACGAAAACAAAGAAUUCUUUUGU-5'(SEQ ID NO:422)
KRAS-2048靶:5'-GCATTGCTTTTGTTTCTTAAGAAAACA-3'(SEQ ID NO:1828)
5'-UUUGUUUCUUAAGAAAACAAACUct-3'(SEQ ID NO:1126)
3'-GAAAACAAAGAAUUCUUUUGUUUGAGA-5'(SEQ ID NO:423)
KRAS-2054靶:5'-CTTTTGTTTCTTAAGAAAACAAACTCT-3'(SEQ ID NO:1829)
5'-CUUAAGAAAACAAACUCUUUUUUaa-3'(SEQ ID NO:1127)
3'-AAGAAUUCUUUUGUUUGAGAAAAAAUU-5'(SEQ ID NO:424)
KRAS-2061靶:5'-TTCTTAAGAAAACAAACTCTTTTTTAA-3'(SEQ ID NO:1830)
5'-UUAAGAAAACAAACUCUUUUUUAaa-3'(SEQ ID NO:1128)
3'-AGAAUUCUUUUGUUUGAGAAAAAAUUU-5'(SEQ ID NO:425)
KRAS-2062靶:5'-TCTTAAGAAAACAAACTCTTTTTTAAA-3'(SEQ ID NO:1831)
5'-UAAGAAAACAAACUCUUUUUUAAaa-3'(SEQ ID NO:1129)
3'-GAAUUCUUUUGUUUGAGAAAAAAUUUU-5'(SEQ ID NO:426)
KRAS-2063靶:5'-CTTAAGAAAACAAACTCTTTTTTAAAA-3'(SEQ ID NO:1832)
5'-AAGAAAACAAACUCUUUUUUAAAaa-3'(SEQ ID NO:1130)
3'-AAUUCUUUUGUUUGAGAAAAAAUUUUU-5'(SEQ ID NO:427)
KRAS-2064靶:5'-TTAAGAAAACAAACTCTTTTTTAAAAA-3'(SEQ ID NO:1833)
5'-AGAAAACAAACUCUUUUUUAAAAat-3'(SEQ ID NO:1131)
3'-AUUCUUUUGUUUGAGAAAAAAUUUUUA-5'(SEQ ID NO:428)
KRAS-2065靶:5'-TAAGAAAACAAACTCTTTTTTAAAAAT-3'(SEQ ID NO:1834)
5'-GAAAACAAACUCUUUUUUAAAAAtt-3'(SEQ ID NO:1132)
3'-UUCUUUUGUUUGAGAAAAAAUUUUUAA-5'(SEQ ID NO:429)
KRAS-2066靶:5'-AAGAAAACAAACTCTTTTTTAAAAATT-3'(SEQ ID NO:1835)
5'-AAAACAAACUCUUUUUUAAAAAUta-3'(SEQ ID NO:1133)
3'-UCUUUUGUUUGAGAAAAAAUUUUUAAU-5'(SEQ ID NO:430)
KRAS-2067靶:5'-AGAAAACAAACTCTTTTTTAAAAATTA-3'(SEQ ID NO:1836)
5'-CAAACUCUUUUUUAAAAAUUACUtt-3'(SEQ ID NO:1134)
3'-UUGUUUGAGAAAAAAUUUUUAAUGAAA-5'(SEQ ID NO:431)
KRAS-2071靶:5'-AACAAACTCTTTTTTAAAAATTACTTT-3'(SEQ ID NO:1837)
5'-CUUUUUUAAAAAUUACUUUUAAAta-3'(SEQ ID NO:1135)
3'-GAGAAAAAAUUUUUAAUGAAAAUUUAU-5'(SEQ ID NO:432)
KRAS-2077靶:5'-CTCTTTTTTAAAAATTACTTTTAAATA-3'(SEQ ID NO:1838)
5'-UUUUUUAAAAAUUACUUUUAAAUat-3'(SEQ ID NO:1136)
3'-AGAAAAAAUUUUUAAUGAAAAUUUAUA-5'(SEQ ID NO:433)
KRAS-2078靶:5'-TCTTTTTTAAAAATTACTTTTAAATAT-3'(SEQ ID NO:1839)
5'-UUUUUAAAAAUUACUUUUAAAUAtt-3'(SEQ ID NO:1137)
3'-GAAAAAAUUUUUAAUGAAAAUUUAUAA-5'(SEQ ID NO:434)
KRAS-2079靶:5'-CTTTTTTAAAAATTACTTTTAAATATT-3'(SEQ ID NO:1840)
5'-UUUUAAAAAUUACUUUUAAAUAUta-3'(SEQ ID NO:1138)
3'-AAAAAAUUUUUAAUGAAAAUUUAUAAU-5'(SEQ ID NO:435)
KRAS-2080靶:5'-TTTTTTAAAAATTACTTTTAAATATTA-3'(SEQ ID NO:1841)
5'-UUUAAAAAUUACUUUUAAAUAUUaa-3'(SEQ ID NO:1139)
3'-AAAAAUUUUUAAUGAAAAUUUAUAAUU-5'(SEQ ID NO:436)
KRAS-2081靶:5'-TTTTTAAAAATTACTTTTAAATATTAA-3'(SEQ ID NO:1842)
5'-UUAAAAAUUACUUUUAAAUAUUAac-3'(SEQ ID NO:1140)
3'-AAAAUUUUUAAUGAAAAUUUAUAAUUG-5'(SEQ ID NO:437)
KRAS-2082靶:5'-TTTTAAAAATTACTTTTAAATATTAAC-3'(SEQ ID NO:1843)
5'-UAAAAAUUACUUUUAAAUAUUAAct-3'(SEQ ID NO:1141)
3'-AAAUUUUUAAUGAAAAUUUAUAAUUGA-5'(SEQ ID NO:438)
KRAS-2083靶:5'-TTTAAAAATTACTTTTAAATATTAACT-3'(SEQ ID NO:1844)
5'-AAAAAUUACUUUUAAAUAUUAACtc-3'(SEQ ID NO:1142)
3'-AAUUUUUAAUGAAAAUUUAUAAUUGAG-5'(SEQ ID NO:439)
KRAS-2084靶:5'-TTAAAAATTACTTTTAAATATTAACTC-3'(SEQ ID NO:1845)
5'-AAAAUUACUUUUAAAUAUUAACUca-3'(SEQ ID NO:1143)
3'-AUUUUUAAUGAAAAUUUAUAAUUGAGU-5'(SEQ ID NO:440)
KRAS-2085靶:5'-TAAAAATTACTTTTAAATATTAACTCA-3'(SEQ ID NO:1846)
5'-CUUUUAAAUAUUAACUCAAAAGUtg-3'(SEQ ID NO:1144)
3'-AUGAAAAUUUAUAAUUGAGUUUUCAAC-5'(SEQ ID NO:441)
KRAS-2092靶:5'-TACTTTTAAATATTAACTCAAAAGTTG-3'(SEQ ID NO:1847)
5'-UUUUAAAUAUUAACUCAAAAGUUga-3'(SEQ ID NO:1145)
3'-UGAAAAUUUAUAAUUGAGUUUUCAACU-5'(SEQ ID NO:442)
KRAS-2093靶:5'-ACTTTTAAATATTAACTCAAAAGTTGA-3'(SEQ ID NO:1848)
5'-UUAAAUAUUAACUCAAAAGUUGAga-3'(SEQ ID NO:1146)
3'-AAAAUUUAUAAUUGAGUUUUCAACUCU-5'(SEQ ID NO:443)
KRAS-2095靶:5'-TTTTAAATATTAACTCAAAAGTTGAGA-3'(SEQ ID NO:1849)
5'-AAAUAUUAACUCAAAAGUUGAGAtt-3'(SEQ ID NO:1147)
3'-AAUUUAUAAUUGAGUUUUCAACUCUAA-5'(SEQ ID NO:444)
KRAS-2097靶:5'-TTAAATATTAACTCAAAAGTTGAGATT-3'(SEQ ID NO:1850)
5'-AAUAUUAACUCAAAAGUUGAGAUtt-3'(SEQ ID NO:1148)
3'-AUUUAUAAUUGAGUUUUCAACUCUAAA-5'(SEQ ID NO:445)
KRAS-2098靶:5'-TAAATATTAACTCAAAAGTTGAGATTT-3'(SEQ ID NO:1851)
5'-AUAUUAACUCAAAAGUUGAGAUUtt-3'(SEQ ID NO:1149)
3'-UUUAUAAUUGAGUUUUCAACUCUAAAA-5'(SEQ ID NO:446)
KRAS-2099靶:5'-AAATATTAACTCAAAAGTTGAGATTTT-3'(SEQ ID NO:1852)
5'-UAUUAACUCAAAAGUUGAGAUUUtg-3'(SEQ ID NO:1150)
3'-UUAUAAUUGAGUUUUCAACUCUAAAAC-5'(SEQ ID NO:447)
KRAS-2100靶:5'-AATATTAACTCAAAAGTTGAGATTTTG-3'(SEQ ID NO:1853)
5'-UGUGCCAAGACAUUAAUUUUUUUtt-3'(SEQ ID NO:1151)
3'-CCACACGGUUCUGUAAUUAAAAAAAAA-5'(SEQ ID NO:448)
KRAS-2134靶:5'-GGTGTGCCAAGACATTAATTTTTTTTT-3'(SEQ ID NO:1854)
5'-CAAGACAUUAAUUUUUUUUUUAAac-3'(SEQ ID NO:1152)
3'-CGGUUCUGUAAUUAAAAAAAAAAUUUG-5'(SEQ ID NO:449)
KRAS-2139靶:5'-GCCAAGACATTAATTTTTTTTTTAAAC-3'(SEQ ID NO:1855)
5'-AAGACAUUAAUUUUUUUUUUAAAca-3'(SEQ ID NO:1153)
3'-GGUUCUGUAAUUAAAAAAAAAAUUUGU-5'(SEQ ID NO:450)
KRAS-2140靶:5'-CCAAGACATTAATTTTTTTTTTAAACA-3'(SEQ ID NO:1856)
5'-UUAAUUUUUUUUUUAAACAAUGAag-3'(SEQ ID NO:1154)
3'-GUAAUUAAAAAAAAAAUUUGUUACUUC-5'(SEQ ID NO:451)
KRAS-2146靶:5'-CATTAATTTTTTTTTTAAACAATGAAG-3'(SEQ ID NO:1857)
5'-UAAUUUUUUUUUUAAACAAUGAAgt-3'(SEQ ID NO:1155)
3'-UAAUUAAAAAAAAAAUUUGUUACUUCA-5'(SEQ ID NO:452)
KRAS-2147靶:5'-ATTAATTTTTTTTTTAAACAATGAAGT-3'(SEQ ID NO:1858)
5'-AUUUUUUUUUUAAACAAUGAAGUga-3'(SEQ ID NO:1156)
3'-AUUAAAAAAAAAAUUUGUUACUUCACU-5'(SEQ ID NO:453)
KRAS-2149靶:5'-TAATTTTTTTTTTAAACAATGAAGTGA-3'(SEQ ID NO:1859)
5'-UUUUUUUUUAAACAAUGAAGUGAaa-3'(SEQ ID NO:1157)
3'-UAAAAAAAAAAUUUGUUACUUCACUUU-5'(SEQ ID NO:454)
KRAS-2151靶:5'-ATTTTTTTTTTAAACAATGAAGTGAAA-3'(SEQ ID NO:1860)
5'-UUUUUUUUAAACAAUGAAGUGAAaa-3'(SEQ ID NO:1158)
3'-AAAAAAAAAAUUUGUUACUUCACUUUU-5'(SEQ ID NO:455)
KRAS-2152靶:5'-TTTTTTTTTTAAACAATGAAGTGAAAA-3'(SEQ ID NO:1861)
5'-UUUUUUUAAACAAUGAAGUGAAAaa-3'(SEQ ID NO:1159)
3'-AAAAAAAAAUUUGUUACUUCACUUUUU-5'(SEQ ID NO:456)
KRAS-2153靶:5'-TTTTTTTTTAAACAATGAAGTGAAAAA-3'(SEQ ID NO:1862)
5'-UUUUUUAAACAAUGAAGUGAAAAag-3'(SEQ ID NO:1160)
3'-AAAAAAAAUUUGUUACUUCACUUUUUC-5'(SEQ ID NO:457)
KRAS-2154靶:5'-TTTTTTTTAAACAATGAAGTGAAAAAG-3'(SEQ ID NO:1863)
5'-UUUUUAAACAAUGAAGUGAAAAAgt-3'(SEQ ID NO:1161)
3'-AAAAAAAUUUGUUACUUCACUUUUUCA-5'(SEQ ID NO:458)
KRAS-2155靶:5'-TTTTTTTAAACAATGAAGTGAAAAAGT-3'(SEQ ID NO:1864)
5'-UUUAAACAAUGAAGUGAAAAAGUtt-3'(SEQ ID NO:1162)
3'-AAAAAUUUGUUACUUCACUUUUUCAAA-5'(SEQ ID NO:459)
KRAS-2157靶:5'-TTTTTAAACAATGAAGTGAAAAAGTTT-3'(SEQ ID NO:1865)
5'-UUAAACAAUGAAGUGAAAAAGUUtt-3'(SEQ ID NO:1163)
3'-AAAAUUUGUUACUUCACUUUUUCAAAA-5'(SEQ ID NO:460)
KRAS-2158靶:5'-TTTTAAACAATGAAGTGAAAAAGTTTT-3'(SEQ ID NO:1866)
5'-UAAACAAUGAAGUGAAAAAGUUUta-3'(SEQ ID NO:1164)
3'-AAAUUUGUUACUUCACUUUUUCAAAAU-5'(SEQ ID NO:461)
KRAS-2159靶:5'-TTTAAACAATGAAGTGAAAAAGTTTTA-3'(SEQ ID NO:1867)
5'-GAAGUGAAAAAGUUUUACAAUCUct-3'(SEQ ID NO:1165)
3'-UACUUCACUUUUUCAAAAUGUUAGAGA-5'(SEQ ID NO:462)
KRAS-2167靶:5'-ATGAAGTGAAAAAGTTTTACAATCTCT-3'(SEQ ID NO:1868)
5'-AAAAAGUUUUACAAUCUCUAGGUtt-3'(SEQ ID NO:1166)
3'-ACUUUUUCAAAAUGUUAGAGAUCCAAA-5'(SEQ ID NO:463)
KRAS-2173靶:5'-TGAAAAAGTTTTACAATCTCTAGGTTT-3'(SEQ ID NO:1869)
5'-AAAAGUUUUACAAUCUCUAGGUUtg-3'(SEQ ID NO:1167)
3'-CUUUUUCAAAAUGUUAGAGAUCCAAAC-5'(SEQ ID NO:464)
KRAS-2174靶:5'-GAAAAAGTTTTACAATCTCTAGGTTTG-3'(SEQ ID NO:1870)
5'-AAAGUUUUACAAUCUCUAGGUUUgg-3'(SEQ ID NO:1168)
3'-UUUUUCAAAAUGUUAGAGAUCCAAACC-5'(SEQ ID NO:465)
KRAS-2175靶:5'-AAAAAGTTTTACAATCTCTAGGTTTGG-3'(SEQ ID NO:1871)
5'-UGGUUAAAUUAACAUUGCAUAAAca-3'(SEQ ID NO:1169)
3'-UGACCAAUUUAAUUGUAACGUAUUUGU-5'(SEQ ID NO:466)
KRAS-2216靶:5'-ACTGGTTAAATTAACATTGCATAAACA-3'(SEQ ID NO:1872)
5'-GGUUAAAUUAACAUUGCAUAAACac-3'(SEQ ID NO:1170)
3'-GACCAAUUUAAUUGUAACGUAUUUGUG-5'(SEQ ID NO:467)
KRAS-2217靶:5'-CTGGTTAAATTAACATTGCATAAACAC-3'(SEQ ID NO:1873)
5'-GUUAAAUUAACAUUGCAUAAACAct-3'(SEQ ID NO:1171)
3'-ACCAAUUUAAUUGUAACGUAUUUGUGA-5'(SEQ ID NO:468)
KRAS-2218靶:5'-TGGTTAAATTAACATTGCATAAACACT-3'(SEQ ID NO:1874)
5'-AUUGCAUAAACACUUUUCAAGUCtg-3'(SEQ ID NO:1172)
3'-UGUAACGUAUUUGUGAAAAGUUCAGAC-5'(SEQ ID NO:469)
KRAS-2229靶:5'-ACATTGCATAAACACTTTTCAAGTCTG-3'(SEQ ID NO:1875)
5'-AAGUCUGAUCCAUAUUUAAUAAUgc-3'(SEQ ID NO:1173)
3'-AGUUCAGACUAGGUAUAAAUUAUUACG-5'(SEQ ID NO:470)
KRAS-2247靶:5'-TCAAGTCTGATCCATATTTAATAATGC-3'(SEQ ID NO:1876)
5'-CAUAUUUAAUAAUGCUUUAAAAUaa-3'(SEQ ID NO:1174)
3'-AGGUAUAAAUUAUUACGAAAUUUUAUU-5'(SEQ ID NO:471)
KRAS-2257靶:5'-TCCATATTTAATAATGCTTTAAAATAA-3'(SEQ ID NO:1877)
5'-AUAUUUAAUAAUGCUUUAAAAUAaa-3'(SEQ ID NO:1175)
3'-GGUAUAAAUUAUUACGAAAUUUUAUUU-5'(SEQ ID NO:472)
KRAS-2258靶:5'-CCATATTTAATAATGCTTTAAAATAAA-3'(SEQ ID NO:1878)
5'-UAUUUAAUAAUGCUUUAAAAUAAaa-3'(SEQ ID NO:1176)
3'-GUAUAAAUUAUUACGAAAUUUUAUUUU-5'(SEQ ID NO:473)
KRAS-2259靶:5'-CATATTTAATAATGCTTTAAAATAAAA-3'(SEQ ID NO:1879)
5'-AUUUAAUAAUGCUUUAAAAUAAAaa-3'(SEQ ID NO:1177)
3'-UAUAAAUUAUUACGAAAUUUUAUUUUU-5'(SEQ ID NO:474)
KRAS-2260靶:5'-ATATTTAATAATGCTTTAAAATAAAAA-3'(SEQ ID NO:1880)
5'-UUUAAUAAUGCUUUAAAAUAAAAat-3'(SEQ ID NO:1178)
3'-AUAAAUUAUUACGAAAUUUUAUUUUUA-5'(SEQ ID NO:475)
KRAS-2261靶:5'-TATTTAATAATGCTTTAAAATAAAAAT-3'(SEQ ID NO:1881)
5'-UUAAUAAUGCUUUAAAAUAAAAAta-3'(SEQ ID NO:1179)
3'-UAAAUUAUUACGAAAUUUUAUUUUUAU-5'(SEQ ID NO:476)
KRAS-2262靶:5'-ATTTAATAATGCTTTAAAATAAAAATA-3'(SEQ ID NO:1882)
5'-AAUAAUGCUUUAAAAUAAAAAUAaa-3'(SEQ ID NO:1180)
3'-AAUUAUUACGAAAUUUUAUUUUUAUUU-5'(SEQ ID NO:477)
KRAS-2264靶:5'-TTAATAATGCTTTAAAATAAAAATAAA-3'(SEQ ID NO:1883)
5'-AUAAUGCUUUAAAAUAAAAAUAAaa-3'(SEQ ID NO:1181)
3'-AUUAUUACGAAAUUUUAUUUUUAUUUU-5'(SEQ ID NO:478)
KRAS-2265靶:5'-TAATAATGCTTTAAAATAAAAATAAAA-3'(SEQ ID NO:1884)
5'-UAAUGCUUUAAAAUAAAAAUAAAaa-3'(SEQ ID NO:1182)
3'-UUAUUACGAAAUUUUAUUUUUAUUUUU-5'(SEQ ID NO:479)
KRAS-2266靶:5'-AATAATGCTTTAAAATAAAAATAAAAA-3'(SEQ ID NO:1885)
5'-AAUGCUUUAAAAUAAAAAUAAAAac-3'(SEQ ID NO:1183)
3'-UAUUACGAAAUUUUAUUUUUAUUUUUG-5'(SEQ ID NO:480)
KRAS-2267靶:5'-ATAATGCTTTAAAATAAAAATAAAAAC-3'(SEQ ID NO:1886)
5'-UAAAAUAAAAAUAAAAACAAUCCtt-3'(SEQ ID NO:1184)
3'-AAAUUUUAUUUUUAUUUUUGUUAGGAA-5'(SEQ ID NO:481)
KRAS-2274靶:5'-TTTAAAATAAAAATAAAAACAATCCTT-3'(SEQ ID NO:1887)
5'-AAAAAUAAAAACAAUCCUUUUGAta-3'(SEQ ID NO:1185)
3'-UAUUUUUAUUUUUGUUAGGAAAACUAU-5'(SEQ ID NO:482)
KRAS-2280靶:5'-ATAAAAATAAAAACAATCCTTTTGATA-3'(SEQ ID NO:1888)
5'-AAAAUAAAAACAAUCCUUUUGAUaa-3'(SEQ ID NO:1186)
3'-AUUUUUAUUUUUGUUAGGAAAACUAUU-5'(SEQ ID NO:483)
KRAS-2281靶:5'-TAAAAATAAAAACAATCCTTTTGATAA-3'(SEQ ID NO:1889)
5'-AAAUAAAAACAAUCCUUUUGAUAaa-3'(SEQ ID NO:1187)
3'-UUUUUAUUUUUGUUAGGAAAACUAUUU-5'(SEQ ID NO:484)
KRAS-2282靶:5'-AAAAATAAAAACAATCCTTTTGATAAA-3'(SEQ ID NO:1890)
5'-AAUAAAAACAAUCCUUUUGAUAAat-3'(SEQ ID NO:1188)
3'-UUUUAUUUUUGUUAGGAAAACUAUUUA-5'(SEQ ID NO:485)
KRAS-2283靶:5'-AAAATAAAAACAATCCTTTTGATAAAT-3'(SEQ ID NO:1891)
5'-AUAAAAACAAUCCUUUUGAUAAAtt-3'(SEQ ID NO:1189)
3'-UUUAUUUUUGUUAGGAAAACUAUUUAA-5'(SEQ ID NO:486)
KRAS-2284靶:5'-AAATAAAAACAATCCTTTTGATAAATT-3'(SEQ ID NO:1892)
5'-UAAAAACAAUCCUUUUGAUAAAUtt-3'(SEQ ID NO:1190)
3'-UUAUUUUUGUUAGGAAAACUAUUUAAA-5'(SEQ ID NO:487)
KRAS-2285靶:5'-AATAAAAACAATCCTTTTGATAAATTT-3'(SEQ ID NO:1893)
5'-AAAAACAAUCCUUUUGAUAAAUUta-3'(SEQ ID NO:1191)
3'-UAUUUUUGUUAGGAAAACUAUUUAAAU-5'(SEQ ID NO:488)
KRAS-2286靶:5'-ATAAAAACAATCCTTTTGATAAATTTA-3'(SEQ ID NO:1894)
5'-AAAACAAUCCUUUUGAUAAAUUUaa-3'(SEQ ID NO:1192)
3'-AUUUUUGUUAGGAAAACUAUUUAAAUU-5'(SEQ ID NO:489)
KRAS-2287靶:5'-TAAAAACAATCCTTTTGATAAATTTAA-3'(SEQ ID NO:1895)
5'-CAAUCCUUUUGAUAAAUUUAAAAtg-3'(SEQ ID NO:1193)
3'-UUGUUAGGAAAACUAUUUAAAUUUUAC-5'(SEQ ID NO:490)
KRAS-2291靶:5'-AACAATCCTTTTGATAAATTTAAAATG-3'(SEQ ID NO:1896)
5'-CUUUUGAUAAAUUUAAAAUGUUAct-3'(SEQ ID NO:1194)
3'-AGGAAAACUAUUUAAAUUUUACAAUGA-5'(SEQ ID NO:491)
KRAS-2296靶:5'-TCCTTTTGATAAATTTAAAATGTTACT-3'(SEQ ID NO:1897)
5'-UUUUGAUAAAUUUAAAAUGUUACtt-3'(SEQ ID NO:1195)
3'-GGAAAACUAUUUAAAUUUUACAAUGAA-5'(SEQ ID NO:492)
KRAS-2297靶:5'-CCTTTTGATAAATTTAAAATGTTACTT-3'(SEQ ID NO:1898)
5'-UUUGAUAAAUUUAAAAUGUUACUta-3'(SEQ ID NO:1196)
3'-GAAAACUAUUUAAAUUUUACAAUGAAU-5'(SEQ ID NO:493)
KRAS-2298靶:5'-CTTTTGATAAATTTAAAATGTTACTTA-3'(SEQ ID NO:1899)
5'-AUAAAUUUAAAAUGUUACUUAUUtt-3'(SEQ ID NO:1197)
3'-ACUAUUUAAAUUUUACAAUGAAUAAAA-5'(SEQ ID NO:494)
KRAS-2302靶:5'-TGATAAATTTAAAATGTTACTTATTTT-3'(SEQ ID NO:1900)
5'-UAAAUUUAAAAUGUUACUUAUUUta-3'(SEQ ID NO:1198)
3'-CUAUUUAAAUUUUACAAUGAAUAAAAU-5'(SEQ ID NO:495)
KRAS-2303靶:5'-GATAAATTTAAAATGTTACTTATTTTA-3'(SEQ ID NO:1901)
5'-AAAUUUAAAAUGUUACUUAUUUUaa-3'(SEQ ID NO:1199)
3'-UAUUUAAAUUUUACAAUGAAUAAAAUU-5'(SEQ ID NO:496)
KRAS-2304靶:5'-ATAAATTTAAAATGTTACTTATTTTAA-3'(SEQ ID NO:1902)
5'-AAUUUAAAAUGUUACUUAUUUUAaa-3'(SEQ ID NO:1200)
3'-AUUUAAAUUUUACAAUGAAUAAAAUUU-5'(SEQ ID NO:497)
KRAS-2305靶:5'-TAAATTTAAAATGTTACTTATTTTAAA-3'(SEQ ID NO:1903)
5'-AUUUAAAAUGUUACUUAUUUUAAaa-3'(SEQ ID NO:1201)
3'-UUUAAAUUUUACAAUGAAUAAAAUUUU-5'(SEQ ID NO:498)
KRAS-2306靶:5'-AAATTTAAAATGTTACTTATTTTAAAA-3'(SEQ ID NO:1904)
5'-UUUAAAAUGUUACUUAUUUUAAAat-3'(SEQ ID NO:1202)
3'-UUAAAUUUUACAAUGAAUAAAAUUUUA-5'(SEQ ID NO:499)
KRAS-2307靶:5'-AATTTAAAATGTTACTTATTTTAAAAT-3'(SEQ ID NO:1905)
5'-UAAAAUGUUACUUAUUUUAAAAUaa-3'(SEQ ID NO:1203)
3'-AAAUUUUACAAUGAAUAAAAUUUUAUU-5'(SEQ ID NO:500)
KRAS-2309靶:5'-TTTAAAATGTTACTTATTTTAAAATAA-3'(SEQ ID NO:1906)
5'-AAAAUGUUACUUAUUUUAAAAUAaa-3'(SEQ ID NO:1204)
3'-AAUUUUACAAUGAAUAAAAUUUUAUUU-5'(SEQ ID NO:501)
KRAS-2310靶:5'-TTAAAATGTTACTTATTTTAAAATAAA-3'(SEQ ID NO:1907)
5'-AAAUGUUACUUAUUUUAAAAUAAat-3'(SEQ ID NO:1205)
3'-AUUUUACAAUGAAUAAAAUUUUAUUUA-5'(SEQ ID NO:502)
KRAS-2311靶:5'-TAAAATGTTACTTATTTTAAAATAAAT-3'(SEQ ID NO:1908)
5'-AAUGUUACUUAUUUUAAAAUAAAtg-3'(SEQ ID NO:1206)
3'-UUUUACAAUGAAUAAAAUUUUAUUUAC-5'(SEQ ID NO:503)
KRAS-2312靶:5'-AAAATGTTACTTATTTTAAAATAAATG-3'(SEQ ID NO:1909)
5'-AUGUUACUUAUUUUAAAAUAAAUga-3'(SEQ ID NO:1207)
3'-UUUACAAUGAAUAAAAUUUUAUUUACU-5'(SEQ ID NO:504)
KRAS-2313靶:5'-AAATGTTACTTATTTTAAAATAAATGA-3'(SEQ ID NO:1910)
5'-GUUACUUAUUUUAAAAUAAAUGAag-3'(SEQ ID NO:1208)
3'-UACAAUGAAUAAAAUUUUAUUUACUUC-5'(SEQ ID NO:505)
KRAS-2315靶:5'-ATGTTACTTATTTTAAAATAAATGAAG-3'(SEQ ID NO:1911)
5'-UUAUUUUAAAAUAAAUGAAGUGAga-3'(SEQ ID NO:1209)
3'-UGAAUAAAAUUUUAUUUACUUCACUCU-5'(SEQ ID NO:506)
KRAS-2320靶:5'-ACTTATTTTAAAATAAATGAAGTGAGA-3'(SEQ ID NO:1912)
5'-AUUUUAAAAUAAAUGAAGUGAGAtg-3'(SEQ ID NO:1210)
3'-AAUAAAAUUUUAUUUACUUCACUCUAC-5'(SEQ ID NO:507)
KRAS-2322靶:5'-TTATTTTAAAATAAATGAAGTGAGATG-3'(SEQ ID NO:1913)
5'-UUUUAAAAUAAAUGAAGUGAGAUgg-3'(SEQ ID NO:1211)
3'-AUAAAAUUUUAUUUACUUCACUCUACC-5'(SEQ ID NO:508)
KRAS-2323靶:5'-TATTTTAAAATAAATGAAGTGAGATGG-3'(SEQ ID NO:1914)
5'-UAAAAUAAAUGAAGUGAGAUGGCat-3'(SEQ ID NO:1212)
3'-AAAUUUUAUUUACUUCACUCUACCGUA-5'(SEQ ID NO:509)
KRAS-2326靶:5'-TTTAAAATAAATGAAGTGAGATGGCAT-3'(SEQ ID NO:1915)
5'-AAAAUAAAUGAAGUGAGAUGGCAtg-3'(SEQ ID NO:1213)
3'-AAUUUUAUUUACUUCACUCUACCGUAC-5'(SEQ ID NO:510)
KRAS-2327靶:5'-TTAAAATAAATGAAGTGAGATGGCATG-3'(SEQ ID NO:1916)
5'-CAUUUCUUCAUGUUAAAAGAAGUca-3'(SEQ ID NO:1214)
3'-AGGUAAAGAAGUACAAUUUUCUUCAGU-5'(SEQ ID NO:511)
KRAS-2447靶:5'-TCCATTTCTTCATGTTAAAAGAAGTCA-3'(SEQ ID NO:1917)
5'-AUUUCUUCAUGUUAAAAGAAGUCat-3'(SEQ ID NO:1215)
3'-GGUAAAGAAGUACAAUUUUCUUCAGUA-5'(SEQ ID NO:512)
KRAS-2448靶:5'-CCATTTCTTCATGTTAAAAGAAGTCAT-3'(SEQ ID NO:1918)
5'-CAAACUCUUAGUUUUUUUUUUUUac-3'(SEQ ID NO:1216)
3'-GAGUUUGAGAAUCAAAAAAAAAAAAUG-5'(SEQ ID NO:513)
KRAS-2475靶:5'-CTCAAACTCTTAGTTTTTTTTTTTTAC-3'(SEQ ID NO:1919)
5'-GUUUUUUUUUUUUACAACUAUGUaa-3'(SEQ ID NO:1217)
3'-AUCAAAAAAAAAAAAUGUUGAUACAUU-5'(SEQ ID NO:514)
KRAS-2485靶:5'-TAGTTTTTTTTTTTTACAACTATGTAA-3'(SEQ ID NO:1920)
5'-UUUUUUUUUUUUACAACUAUGUAat-3'(SEQ ID NO:1218)
3'-UCAAAAAAAAAAAAUGUUGAUACAUUA-5'(SEQ ID NO:515)
KRAS-2486靶:5'-AGTTTTTTTTTTTTACAACTATGTAAT-3'(SEQ ID NO:1921)
5'-UUUUUUUUUUUACAACUAUGUAAtt-3'(SEQ ID NO:1219)
3'-CAAAAAAAAAAAAUGUUGAUACAUUAA-5'(SEQ ID NO:516)
KRAS-2487靶:5'-GTTTTTTTTTTTTACAACTATGTAATT-3'(SEQ ID NO:1922)
5'-UUUUUUUUUUACAACUAUGUAAUtt-3'(SEQ ID NO:1220)
3'-AAAAAAAAAAAAUGUUGAUACAUUAAA-5'(SEQ ID NO:517)
KRAS-2488靶:5'-TTTTTTTTTTTTACAACTATGTAATTT-3'(SEQ ID NO:1923)
5'-UUUUUUUUUACAACUAUGUAAUUta-3'(SEQ ID NO:1221)
3'-AAAAAAAAAAAUGUUGAUACAUUAAAU-5'(SEQ ID NO:518)
KRAS-2489靶:5'-TTTTTTTTTTTACAACTATGTAATTTA-3'(SEQ ID NO:1924)
5'-UUUUUUUUACAACUAUGUAAUUUat-3'(SEQ ID NO:1222)
3'-AAAAAAAAAAUGUUGAUACAUUAAAUA-5'(SEQ ID NO:519)
KRAS-2490靶:5'-TTTTTTTTTTACAACTATGTAATTTAT-3'(SEQ ID NO:1925)
5'-UUUUUUUACAACUAUGUAAUUUAta-3'(SEQ ID NO:1223)
3'-AAAAAAAAAUGUUGAUACAUUAAAUAU-5'(SEQ ID NO:520)
KRAS-2491靶:5'-TTTTTTTTTACAACTATGTAATTTATA-3'(SEQ ID NO:1926)
5'-UUUUUUACAACUAUGUAAUUUAUat-3'(SEQ ID NO:1224)
3'-AAAAAAAAUGUUGAUACAUUAAAUAUA-5'(SEQ ID NO:521)
KRAS-2492靶:5'-TTTTTTTTACAACTATGTAATTTATAT-3'(SEQ ID NO:1927)
5'-UUUUUACAACUAUGUAAUUUAUAtt-3'(SEQ ID NO:1225)
3'-AAAAAAAUGUUGAUACAUUAAAUAUAA-5'(SEQ ID NO:522)
KRAS-2493靶:5'-TTTTTTTACAACTATGTAATTTATATT-3'(SEQ ID NO:1928)
5'-UUUUACAACUAUGUAAUUUAUAUtc-3'(SEQ ID NO:1226)
3'-AAAAAAUGUUGAUACAUUAAAUAUAAG-5'(SEQ ID NO:523)
KRAS-2494靶:5'-TTTTTTACAACTATGTAATTTATATTC-3'(SEQ ID NO:1929)
5'-UUUACAACUAUGUAAUUUAUAUUcc-3'(SEQ ID NO:1227)
3'-AAAAAUGUUGAUACAUUAAAUAUAAGG-5'(SEQ ID NO:524)
KRAS-2495靶:5'-TTTTTACAACTATGTAATTTATATTCC-3'(SEQ ID NO:1930)
5'-CUAUGUAAUUUAUAUUCCAUUUAca-3'(SEQ ID NO:1228)
3'-UUGAUACAUUAAAUAUAAGGUAAAUGU-5'(SEQ ID NO:525)
KRAS-2502靶:5'-AACTATGTAATTTATATTCCATTTACA-3'(SEQ ID NO:1931)
5'-UAUGUAAUUUAUAUUCCAUUUACat-3'(SEQ ID NO:1229)
3'-UGAUACAUUAAAUAUAAGGUAAAUGUA-5'(SEQ ID NO:526)
KRAS-2503靶:5'-ACTATGTAATTTATATTCCATTTACAT-3'(SEQ ID NO:1932)
5'-AUGUAAUUUAUAUUCCAUUUACAta-3'(SEQ ID NO:1230)
3'-GAUACAUUAAAUAUAAGGUAAAUGUAU-5'(SEQ ID NO:527)
KRAS-2504靶:5'-CTATGTAATTTATATTCCATTTACATA-3'(SEQ ID NO:1933)
5'-UUUAUAUUCCAUUUACAUAAGGAta-3'(SEQ ID NO:1231)
3'-UUAAAUAUAAGGUAAAUGUAUUCCUAU-5'(SEQ ID NO:528)
KRAS-2510靶:5'-AATTTATATTCCATTTACATAAGGATA-3'(SEQ ID NO:1934)
5'-UUAUAUUCCAUUUACAUAAGGAUac-3'(SEQ ID NO:1232)
3'-UAAAUAUAAGGUAAAUGUAUUCCUAUG-5'(SEQ ID NO:529)
KRAS-2511靶:5'-ATTTATATTCCATTTACATAAGGATAC-3'(SEQ ID NO:1935)
5'-UAUAUUCCAUUUACAUAAGGAUAca-3'(SEQ ID NO:1233)
3'-AAAUAUAAGGUAAAUGUAUUCCUAUGU-5'(SEQ ID NO:530)
KRAS-2512靶:5'-TTTATATTCCATTTACATAAGGATACA-3'(SEQ ID NO:1936)
5'-AUAUUCCAUUUACAUAAGGAUACac-3'(SEQ ID NO:1234)
3'-AAUAUAAGGUAAAUGUAUUCCUAUGUG-5'(SEQ ID NO:531)
KRAS-2513靶:5'-TTATATTCCATTTACATAAGGATACAC-3'(SEQ ID NO:1937)
5'-CAUAAGGAUACACUUAUUUGUCAag-3'(SEQ ID NO:1235)
3'-AUGUAUUCCUAUGUGAAUAAACAGUUC-5'(SEQ ID NO:532)
KRAS-2525靶:5'-TACATAAGGATACACTTATTTGTCAAG-3'(SEQ ID NO:1938)
5'-AGGAUACACUUAUUUGUCAAGCUca-3'(SEQ ID NO:1236)
3'-AUUCCUAUGUGAAUAAACAGUUCGAGU-5'(SEQ ID NO:533)
KRAS-2529靶:5'-TAAGGATACACTTATTTGTCAAGCTCA-3'(SEQ ID NO:1939)
5'-CUGUAAAUUUUUAACCUAUGUUAca-3'(SEQ ID NO:1237)
3'-UAGACAUUUAAAAAUUGGAUACAAUGU-5'(SEQ ID NO:534)
KRAS-2561靶:5'-ATCTGTAAATTTTTAACCTATGTTACA-3'(SEQ ID NO:1940)
5'-UGUAAAUUUUUAACCUAUGUUACac-3'(SEQ ID NO:1238)
3'-AGACAUUUAAAAAUUGGAUACAAUGUG-5'(SEQ ID NO:535)
KRAS-2562靶:5'-TCTGTAAATTTTTAACCTATGTTACAC-3'(SEQ ID NO:1941)
5'-GUAAAUUUUUAACCUAUGUUACAcc-3'(SEQ ID NO:1239)
3'-GACAUUUAAAAAUUGGAUACAAUGUGG-5'(SEQ ID NO:536)
KRAS-2563靶:5'-CTGTAAATTTTTAACCTATGTTACACC-3'(SEQ ID NO:1942)
5'-CAAGAGGUGAAGUUUAUAUUUGAat-3'(SEQ ID NO:1240)
3'-ACGUUCUCCACUUCAAAUAUAAACUUA-5'(SEQ ID NO:537)
KRAS-2619靶:5'-TGCAAGAGGTGAAGTTTATATTTGAAT-3'(SEQ ID NO:1943)
5'-AGAGGUGAAGUUUAUAUUUGAAUat-3'(SEQ ID NO:1241)
3'-GUUCUCCACUUCAAAUAUAAACUUAUA-5'(SEQ ID NO:538)
KRAS-2621靶:5'-CAAGAGGTGAAGTTTATATTTGAATAT-3'(SEQ ID NO:1944)
5'-GAGGUGAAGUUUAUAUUUGAAUAtc-3'(SEQ ID NO:1242)
3'-UUCUCCACUUCAAAUAUAAACUUAUAG-5'(SEQ ID NO:539)
KRAS-2622靶:5'-AAGAGGTGAAGTTTATATTTGAATATC-3'(SEQ ID NO:1945)
5'-GGUGAAGUUUAUAUUUGAAUAUCca-3'(SEQ ID NO:1243)
3'-CUCCACUUCAAAUAUAAACUUAUAGGU-5'(SEQ ID NO:540)
KRAS-2624靶:5'-GAGGTGAAGTTTATATTTGAATATCCA-3'(SEQ ID NO:1946)
5'-GUGAAGUUUAUAUUUGAAUAUCCat-3'(SEQ ID NO:1244)
3'-UCCACUUCAAAUAUAAACUUAUAGGUA-5'(SEQ ID NO:541)
KRAS-2625靶:5'-AGGTGAAGTTTATATTTGAATATCCAT-3'(SEQ ID NO:1947)
5'-GUUUAUAUUUGAAUAUCCAUUCUcg-3'(SEQ ID NO:1245)
3'-UUCAAAUAUAAACUUAUAGGUAAGAGC-5'(SEQ ID NO:542)
KRAS-2630靶:5'-AAGTTTATATTTGAATATCCATTCTCG-3'(SEQ ID NO:1948)
5'-UUGAUGCAGUUUUAAUACUUGUAat-3'(SEQ ID NO:1246)
3'-UGAACUACGUCAAAAUUAUGAACAUUA-5'(SEQ ID NO:543)
KRAS-2718靶:5'-ACTTGATGCAGTTTTAATACTTGTAAT-3'(SEQ ID NO:1949)
5'-GAUGCAGUUUUAAUACUUGUAAUtc-3'(SEQ ID NO:1247)
3'-AACUACGUCAAAAUUAUGAACAUUAAG-5'(SEQ ID NO:544)
KRAS-2720靶:5'-TTGATGCAGTTTTAATACTTGTAATTC-3'(SEQ ID NO:1950)
5'-UUUGACCUAAUCACUAAUUUUCAgg-3'(SEQ ID NO:1248)
3'-CUAAACUGGAUUAGUGAUUAAAAGUCC-5'(SEQ ID NO:545)
KRAS-2871靶:5'-GATTTGACCTAATCACTAATTTTCAGG-3'(SEQ ID NO:1951)
5'-CUAAUCACUAAUUUUCAGGUGGUgg-3'(SEQ ID NO:1249)
3'-UGGAUUAGUGAUUAAAAGUCCACCACC-5'(SEQ ID NO:546)
KRAS-2877靶:5'-ACCTAATCACTAATTTTCAGGTGGTGG-3'(SEQ ID NO:1952)
5'-GUAGGAUUUUUCAAACCUGGUAUga-3'(SEQ ID NO:1250)
3'-GUCAUCCUAAAAAGUUUGGACCAUACU-5'(SEQ ID NO:547)
KRAS-2946靶:5'-CAGTAGGATTTTTCAAACCTGGTATGA-3'(SEQ ID NO:1953)
5'-UGGAAGGAGAAUUUAAUAAAGAUag-3'(SEQ ID NO:1251)
3'-UCACCUUCCUCUUAAAUUAUUUCUAUC-5'(SEQ ID NO:548)
KRAS-2991靶:5'-AGTGGAAGGAGAATTTAATAAAGATAG-3'(SEQ ID NO:1954)
5'-AAGGAGAAUUUAAUAAAGAUAGUgc-3'(SEQ ID NO:1252)
3'-CCUUCCUCUUAAAUUAUUUCUAUCACG-5'(SEQ ID NO:549)
KRAS-2994靶:5'-GGAAGGAGAATTTAATAAAGATAGTGC-3'(SEQ ID NO:1955)
5'-GGAGAAUUUAAUAAAGAUAGUGCtg-3'(SEQ ID NO:1253)
3'-UUCCUCUUAAAUUAUUUCUAUCACGAC-5'(SEQ ID NO:550)
KRAS-2996靶:5'-AAGGAGAATTTAATAAAGATAGTGCTG-3'(SEQ ID NO:1956)
5'-GAGAAUUUAAUAAAGAUAGUGCUga-3'(SEQ ID NO:1254)
3'-UCCUCUUAAAUUAUUUCUAUCACGACU-5'(SEQ ID NO:551)
KRAS-2997靶:5'-AGGAGAATTTAATAAAGATAGTGCTGA-3'(SEQ ID NO:1957)
5'-AUUUAAUAAAGAUAGUGCUGAAAga-3'(SEQ ID NO:1255)
3'-CUUAAAUUAUUUCUAUCACGACUUUCU-5'(SEQ ID NO:552)
KRAS-3001靶:5'-GAATTTAATAAAGATAGTGCTGAAAGA-3'(SEQ ID NO:1958)
5'-CUUAGGUAAUCUAUAACUAGGACta-3'(SEQ ID NO:1256)
3'-AGGAAUCCAUUAGAUAUUGAUCCUGAU-5'(SEQ ID NO:553)
KRAS-3030靶:5'-TCCTTAGGTAATCTATAACTAGGACTA-3'(SEQ ID NO:1959)
5'-UUAGGUAAUCUAUAACUAGGACUac-3'(SEQ ID NO:1257)
3'-GGAAUCCAUUAGAUAUUGAUCCUGAUG-5'(SEQ ID NO:554)
KRAS-3031靶:5'-CCTTAGGTAATCTATAACTAGGACTAC-3'(SEQ ID NO:1960)
5'-CAGUAAUACAUUCCAUUGUUUUAgt-3'(SEQ ID NO:1258)
3'-UUGUCAUUAUGUAAGGUAACAAAAUCA-5'(SEQ ID NO:555)
KRAS-3065靶:5'-AACAGTAATACATTCCATTGTTTTAGT-3'(SEQ ID NO:1961)
5'-GUAAUACAUUCCAUUGUUUUAGUaa-3'(SEQ ID NO:1259)
3'-GUCAUUAUGUAAGGUAACAAAAUCAUU-5'(SEQ ID NO:556)
KRAS-3067靶:5'-CAGTAATACATTCCATTGTTTTAGTAA-3'(SEQ ID NO:1962)
5'-UAAUACAUUCCAUUGUUUUAGUAac-3'(SEQ ID NO:1260)
3'-UCAUUAUGUAAGGUAACAAAAUCAUUG-5'(SEQ ID NO:557)
KRAS-3068靶:5'-AGTAATACATTCCATTGTTTTAGTAAC-3'(SEQ ID NO:1963)
5'-AAUACAUUCCAUUGUUUUAGUAAcc-3'(SEQ ID NO:1261)
3'-CAUUAUGUAAGGUAACAAAAUCAUUGG-5'(SEQ ID NO:558)
KRAS-3069靶:5'-GTAATACATTCCATTGTTTTAGTAACC-3'(SEQ ID NO:1964)
5'-AUUGUUUUAGUAACCAGAAAUCUtc-3'(SEQ ID NO:1262)
3'-GGUAACAAAAUCAUUGGUCUUUAGAAG-5'(SEQ ID NO:559)
KRAS-3079靶:5'-CCATTGTTTTAGTAACCAGAAATCTTC-3'(SEQ ID NO:1965)
5'-CAGAAAUCUUCAUGCAAUGAAAAat-3'(SEQ ID NO:1263)
3'-UGGUCUUUAGAAGUACGUUACUUUUUA-5'(SEQ ID NO:560)
KRAS-3093靶:5'-ACCAGAAATCTTCATGCAATGAAAAAT-3'(SEQ ID NO:1966)
5'-CAUGCAAUGAAAAAUACUUUAAUtc-3'(SEQ ID NO:1264)
3'-AAGUACGUUACUUUUUAUGAAAUUAAG-5'(SEQ ID NO:561)
KRAS-3103靶:5'-TTCATGCAATGAAAAATACTTTAATTC-3'(SEQ ID NO:1967)
5'-UGAAAAAUACUUUAAUUCAUGAAgc-3'(SEQ ID NO:1265)
3'-UUACUUUUUAUGAAAUUAAGUACUUCG-5'(SEQ ID NO:562)
KRAS-3110靶:5'-AATGAAAAATACTTTAATTCATGAAGC-3'(SEQ ID NO:1968)
5'-AAAAAUACUUUAAUUCAUGAAGCtt-3'(SEQ ID NO:1266)
3'-ACUUUUUAUGAAAUUAAGUACUUCGAA-5'(SEQ ID NO:563)
KRAS-3112靶:5'-TGAAAAATACTTTAATTCATGAAGCTT-3'(SEQ ID NO:1969)
5'-AAAAUACUUUAAUUCAUGAAGCUta-3'(SEQ ID NO:1267)
3'-CUUUUUAUGAAAUUAAGUACUUCGAAU-5'(SEQ ID NO:564)
KRAS-3113靶:5'-GAAAAATACTTTAATTCATGAAGCTTA-3'(SEQ ID NO:1970)
5'-CAUGAAGCUUACUUUUUUUUUUUgg-3'(SEQ ID NO:1268)
3'-AAGUACUUCGAAUGAAAAAAAAAAACC-5'(SEQ ID NO:565)
KRAS-3127靶:5'-TTCATGAAGCTTACTTTTTTTTTTTGG-3'(SEQ ID NO:1971)
5'-GAAGCUUACUUUUUUUUUUUGGUgt-3'(SEQ ID NO:1269)
3'-UACUUCGAAUGAAAAAAAAAAACCACA-5'(SEQ ID NO:566)
KRAS-3130靶:5'-ATGAAGCTTACTTTTTTTTTTTGGTGT-3'(SEQ ID NO:1972)
5'-CUUACUUUUUUUUUUUGGUGUCAga-3'(SEQ ID NO:1270)
3'-UCGAAUGAAAAAAAAAAACCACAGUCU-5'(SEQ ID NO:567)
KRAS-3134靶:5'-AGCTTACTTTTTTTTTTTGGTGTCAGA-3'(SEQ ID NO:1973)
5'-CUUUUUUUUUUUGGUGUCAGAGUct-3'(SEQ ID NO:1271)
3'-AUGAAAAAAAAAAACCACAGUCUCAGA-5'(SEQ ID NO:568)
KRAS-3138靶:5'-TACTTTTTTTTTTTGGTGTCAGAGTCT-3'(SEQ ID NO:1974)
5'-UUUUUUUUUUUGGUGUCAGAGUCtc-3'(SEQ ID NO:1272)
3'-UGAAAAAAAAAAACCACAGUCUCAGAG-5'(SEQ ID NO:569)
KRAS-3139靶:5'-ACTTTTTTTTTTTGGTGTCAGAGTCTC-3'(SEQ ID NO:1975)
5'-CUAAUUUUUGUAUUUUUAGGAGAga-3'(SEQ ID NO:1273)
3'-UUGAUUAAAAACAUAAAAAUCCUCUCU-5'(SEQ ID NO:570)
KRAS-3297靶:5'-AACTAATTTTTGTATTTTTAGGAGAGA-3'(SEQ ID NO:1976)
5'-AUUUUUGUAUUUUUAGGAGAGACgg-3'(SEQ ID NO:1274)
3'-AUUAAAAACAUAAAAAUCCUCUCUGCC-5'(SEQ ID NO:571)
KRAS-3300靶:5'-TAATTTTTGTATTTTTAGGAGAGACGG-3'(SEQ ID NO:1977)
5'-CAUUUAUUCAGCAAAUAUUUAUUga-3'(SEQ ID NO:1275)
3'-GAGUAAAUAAGUCGUUUAUAAAUAACU-5'(SEQ ID NO:572)
KRAS-3413靶:5'-CTCATTTATTCAGCAAATATTTATTGA-3'(SEQ ID NO:1978)
5'-UUUAUUCAGCAAAUAUUUAUUGAgt-3'(SEQ ID NO:1276)
3'-GUAAAUAAGUCGUUUAUAAAUAACUCA-5'(SEQ ID NO:573)
KRAS-3415靶:5'-CATTTATTCAGCAAATATTTATTGAGT-3'(SEQ ID NO:1979)
5'-UAUUCAGCAAAUAUUUAUUGAGUgc-3'(SEQ ID NO:1277)
3'-AAAUAAGUCGUUUAUAAAUAACUCACG-5'(SEQ ID NO:574)
KRAS-3417靶:5'-TTTATTCAGCAAATATTTATTGAGTGC-3'(SEQ ID NO:1980)
5'-UUUUAGUUUUGCAAAGAAGGGGUtt-3'(SEQ ID NO:1278)
3'-AUAAAAUCAAAACGUUUCUUCCCCAAA-5'(SEQ ID NO:575)
KRAS-3589靶:5'-TATTTTAGTTTTGCAAAGAAGGGGTTT-3'(SEQ ID NO:1981)
5'-CUAUAAUUGUUUUGCUACGAUUCca-3'(SEQ ID NO:1279)
3'-GAGAUAUUAACAAAACGAUGCUAAGGU-5'(SEQ ID NO:576)
KRAS-3630靶:5'-CTCTATAATTGTTTTGCTACGATTCCA-3'(SEQ ID NO:1982)
5'-CUUUAUGUAAAUCACUUCAUUGUtt-3'(SEQ ID NO:1280)
3'-AUGAAAUACAUUUAGUGAAGUAACAAA-5'(SEQ ID NO:577)
KRAS-3677靶:5'-TACTTTATGTAAATCACTTCATTGTTT-3'(SEQ ID NO:1983)
5'-UUUAUGUAAAUCACUUCAUUGUUtt-3'(SEQ ID NO:1281)
3'-UGAAAUACAUUUAGUGAAGUAACAAAA-5'(SEQ ID NO:578)
KRAS-3678靶:5'-ACTTTATGTAAATCACTTCATTGTTTT-3'(SEQ ID NO:1984)
5'-UUAUGUAAAUCACUUCAUUGUUUta-3'(SEQ ID NO:1282)
3'-GAAAUACAUUUAGUGAAGUAACAAAAU-5'(SEQ ID NO:579)
KRAS-3679靶:5'-CTTTATGTAAATCACTTCATTGTTTTA-3'(SEQ ID NO:1985)
5'-UAUGUAAAUCACUUCAUUGUUUUaa-3'(SEQ ID NO:1283)
3'-AAAUACAUUUAGUGAAGUAACAAAAUU-5'(SEQ ID NO:580)
KRAS-3680靶:5'-TTTATGTAAATCACTTCATTGTTTTAA-3'(SEQ ID NO:1986)
5'-AUGUAAAUCACUUCAUUGUUUUAaa-3'(SEQ ID NO:1284)
3'-AAUACAUUUAGUGAAGUAACAAAAUUU-5'(SEQ ID NO:581)
KRAS-3681靶:5'-TTATGTAAATCACTTCATTGTTTTAAA-3'(SEQ ID NO:1987)
5'-UGUAAAUCACUUCAUUGUUUUAAag-3'(SEQ ID NO:1285)
3'-AUACAUUUAGUGAAGUAACAAAAUUUC-5'(SEQ ID NO:582)
KRAS-3682靶:5'-TATGTAAATCACTTCATTGTTTTAAAG-3'(SEQ ID NO:1988)
5'-GUAAAUCACUUCAUUGUUUUAAAgg-3'(SEQ ID NO:1286)
3'-UACAUUUAGUGAAGUAACAAAAUUUCC-5'(SEQ ID NO:583)
KRAS-3683靶:5'-ATGTAAATCACTTCATTGTTTTAAAGG-3'(SEQ ID NO:1989)
5'-UGUUUUAAAGGAAUAAACUUGAUta-3'(SEQ ID NO:1287)
3'-UAACAAAAUUUCCUUAUUUGAACUAAU-5'(SEQ ID NO:584)
KRAS-3697靶:5'-ATTGTTTTAAAGGAATAAACTTGATTA-3'(SEQ ID NO:1990)
5'-GUUUUAAAGGAAUAAACUUGAUUat-3'(SEQ ID NO:1288)
3'-AACAAAAUUUCCUUAUUUGAACUAAUA-5'(SEQ ID NO:585)
KRAS-3698靶:5'-TTGTTTTAAAGGAATAAACTTGATTAT-3'(SEQ ID NO:1991)
5'-UUAAAGGAAUAAACUUGAUUAUAtt-3'(SEQ ID NO:1289)
3'-AAAAUUUCCUUAUUUGAACUAAUAUAA-5'(SEQ ID NO:586)
KRAS-3701靶:5'-TTTTAAAGGAATAAACTTGATTATATT-3'(SEQ ID NO:1992)
5'-UAAAGGAAUAAACUUGAUUAUAUtg-3'(SEQ ID NO:1290)
3'-AAAUUUCCUUAUUUGAACUAAUAUAAC-5'(SEQ ID NO:587)
KRAS-3702靶:5'-TTTAAAGGAATAAACTTGATTATATTG-3'(SEQ ID NO:1993)
5'-AAAGGAAUAAACUUGAUUAUAUUgt-3'(SEQ ID NO:1291)
3'-AAUUUCCUUAUUUGAACUAAUAUAACA-5'(SEQ ID NO:588)
KRAS-3703靶:5'-TTAAAGGAATAAACTTGATTATATTGT-3'(SEQ ID NO:1994)
5'-AGGAAUAAACUUGAUUAUAUUGUtt-3'(SEQ ID NO:1292)
3'-UUUCCUUAUUUGAACUAAUAUAACAAA-5'(SEQ ID NO:589)
KRAS-3705靶:5'-AAAGGAATAAACTTGATTATATTGTTT-3'(SEQ ID NO:1995)
5'-GGAAUAAACUUGAUUAUAUUGUUtt-3'(SEQ ID NO:1293)
3'-UUCCUUAUUUGAACUAAUAUAACAAAA-5'(SEQ ID NO:590)
KRAS-3706靶:5'-AAGGAATAAACTTGATTATATTGTTTT-3'(SEQ ID NO:1996)
5'-GAAUAAACUUGAUUAUAUUGUUUtt-3'(SEQ ID NO:1294)
3'-UCCUUAUUUGAACUAAUAUAACAAAAA-5'(SEQ ID NO:591)
KRAS-3707靶:5'-AGGAATAAACTTGATTATATTGTTTTT-3'(SEQ ID NO:1997)
5'-AAUAAACUUGAUUAUAUUGUUUUtt-3'(SEQ ID NO:1295)
3'-CCUUAUUUGAACUAAUAUAACAAAAAA-5'(SEQ ID NO:592)
KRAS-3708靶:5'-GGAATAAACTTGATTATATTGTTTTTT-3'(SEQ ID NO:1998)
5'-AUAAACUUGAUUAUAUUGUUUUUtt-3'(SEQ ID NO:1296)
3'-CUUAUUUGAACUAAUAUAACAAAAAAA-5'(SEQ ID NO:593)
KRAS-3709靶:5'-GAATAAACTTGATTATATTGTTTTTTT-3'(SEQ ID NO:1999)
5'-CUUGAUUAUAUUGUUUUUUUAUUtg-3'(SEQ ID NO:1297)
3'-UUGAACUAAUAUAACAAAAAAAUAAAC-5'(SEQ ID NO:594)
KRAS-3714靶:5'-AACTTGATTATATTGTTTTTTTATTTG-3'(SEQ ID NO:2000)
5'-UUGAUUAUAUUGUUUUUUUAUUUgg-3'(SEQ ID NO:1298)
3'-UGAACUAAUAUAACAAAAAAAUAAACC-5'(SEQ ID NO:595)
KRAS-3715靶:5'-ACTTGATTATATTGTTTTTTTATTTGG-3'(SEQ ID NO:2001)
5'-AUUAUAUUGUUUUUUUAUUUGGCat-3'(SEQ ID NO:1299)
3'-ACUAAUAUAACAAAAAAAUAAACCGUA-5'(SEQ ID NO:596)
KRAS-3718靶:5'-TGATTATATTGTTTTTTTATTTGGCAT-3'(SEQ ID NO:2002)
5'-AUUGUUUUUUUAUUUGGCAUAACtg-3'(SEQ ID NO:1300)
3'-UAUAACAAAAAAAUAAACCGUAUUGAC-5'(SEQ ID NO:597)
KRAS-3723靶:5'-ATATTGTTTTTTTATTTGGCATAACTG-3'(SEQ ID NO:2003)
5'-UUGUUUUUUUAUUUGGCAUAACUgt-3'(SEQ ID NO:1301)
3'-AUAACAAAAAAAUAAACCGUAUUGACA-5'(SEQ ID NO:598)
KRAS-3724靶:5'-TATTGTTTTTTTATTTGGCATAACTGT-3'(SEQ ID NO:2004)
5'-UUUUUUAUUUGGCAUAACUGUGAtt-3'(SEQ ID NO:1302)
3'-CAAAAAAAUAAACCGUAUUGACACUAA-5'(SEQ ID NO:599)
KRAS-3728靶:5'-GTTTTTTTATTTGGCATAACTGTGATT-3'(SEQ ID NO:2005)
5'-UUUUUAUUUGGCAUAACUGUGAUtc-3'(SEQ ID NO:1303)
3'-AAAAAAAUAAACCGUAUUGACACUAAG-5'(SEQ ID NO:600)
KRAS-3729靶:5'-TTTTTTTATTTGGCATAACTGTGATTC-3'(SEQ ID NO:2006)
5'-AUAACUGUGAUUCUUUUAGGACAat-3'(SEQ ID NO:1304)
3'-CGUAUUGACACUAAGAAAAUCCUGUUA-5'(SEQ ID NO:601)
KRAS-3741靶:5'-GCATAACTGTGATTCTTTTAGGACAAT-3'(SEQ ID NO:2007)
5'-UGUGAUUCUUUUAGGACAAUUACtg-3'(SEQ ID NO:1305)
3'-UGACACUAAGAAAAUCCUGUUAAUGAC-5'(SEQ ID NO:602)
KRAS-3746靶:5'-ACTGTGATTCTTTTAGGACAATTACTG-3'(SEQ ID NO:2008)
5'-GUGAUUCUUUUAGGACAAUUACUgt-3'(SEQ ID NO:1306)
3'-GACACUAAGAAAAUCCUGUUAAUGACA-5'(SEQ ID NO:603)
KRAS-3747靶:5'-CTGTGATTCTTTTAGGACAATTACTGT-3'(SEQ ID NO:2009)
5'-UGUAUGUCAGAUAUUCAUAUUGAcc-3'(SEQ ID NO:1307)
3'-CCACAUACAGUCUAUAAGUAUAACUGG-5'(SEQ ID NO:604)
KRAS-3783靶:5'-GGTGTATGTCAGATATTCATATTGACC-3'(SEQ ID NO:2010)
5'-GUAUGUCAGAUAUUCAUAUUGACcc-3'(SEQ ID NO:1308)
3'-CACAUACAGUCUAUAAGUAUAACUGGG-5'(SEQ ID NO:605)
KRAS-3784靶:5'-GTGTATGTCAGATATTCATATTGACCC-3'(SEQ ID NO:2011)
5'-AAUGUGUAAUAUUCCAGUUUUCUct-3'(SEQ ID NO:1309)
3'-GUUUACACAUUAUAAGGUCAAAAGAGA-5'(SEQ ID NO:606)
KRAS-3810靶:5'-CAAATGTGTAATATTCCAGTTTTCTCT-3'(SEQ ID NO:2012)
5'-UAAGUAAUUAAAAUAUACUUAAAaa-3'(SEQ ID NO:1310)
3'-GUAUUCAUUAAUUUUAUAUGAAUUUUU-5'(SEQ ID NO:607)
KRAS-3838靶:5'-CATAAGTAATTAAAATATACTTAAAAA-3'(SEQ ID NO:2013)
5'-AAGUAAUUAAAAUAUACUUAAAAat-3'(SEQ ID NO:1311)
3'-UAUUCAUUAAUUUUAUAUGAAUUUUUA-5'(SEQ ID NO:608)
KRAS-3839靶:5'-ATAAGTAATTAAAATATACTTAAAAAT-3'(SEQ ID NO:2014)
5'-AGUAAUUAAAAUAUACUUAAAAAtt-3'(SEQ ID NO:1312)
3'-AUUCAUUAAUUUUAUAUGAAUUUUUAA-5'(SEQ ID NO:609)
KRAS-3840靶:5'-TAAGTAATTAAAATATACTTAAAAATT-3'(SEQ ID NO:2015)
5'-GUAAUUAAAAUAUACUUAAAAAUta-3'(SEQ ID NO:1313)
3'-UUCAUUAAUUUUAUAUGAAUUUUUAAU-5'(SEQ ID NO:610)
KRAS-3841靶:5'-AAGTAATTAAAATATACTTAAAAATTA-3'(SEQ ID NO:2016)
5'-UAAUUAAAAUAUACUUAAAAAUUaa-3'(SEQ ID NO:1314)
3'-UCAUUAAUUUUAUAUGAAUUUUUAAUU-5'(SEQ ID NO:611)
KRAS-3842靶:5'-AGTAATTAAAATATACTTAAAAATTAA-3'(SEQ ID NO:2017)
5'-AAUUAAAAUAUACUUAAAAAUUAat-3'(SEQ ID NO:1315)
3'-CAUUAAUUUUAUAUGAAUUUUUAAUUA-5'(SEQ ID NO:612)
KRAS-3843靶:5'-GTAATTAAAATATACTTAAAAATTAAT-3'(SEQ ID NO:2018)
5'-AUUAAAAUAUACUUAAAAAUUAAta-3'(SEQ ID NO:1316)
3'-AUUAAUUUUAUAUGAAUUUUUAAUUAU-5'(SEQ ID NO:613)
KRAS-3844靶:5'-TAATTAAAATATACTTAAAAATTAATA-3'(SEQ ID NO:2019)
5'-UUAAAAUAUACUUAAAAAUUAAUag-3'(SEQ ID NO:1317)
3'-UUAAUUUUAUAUGAAUUUUUAAUUAUC-5'(SEQ ID NO:614)
KRAS-3845靶:5'-AATTAAAATATACTTAAAAATTAATAG-3'(SEQ ID NO:2020)
5'-UAAAAUAUACUUAAAAAUUAAUAgt-3'(SEQ ID NO:1318)
3'-UAAUUUUAUAUGAAUUUUUAAUUAUCA-5'(SEQ ID NO:615)
KRAS-3846靶:5'-ATTAAAATATACTTAAAAATTAATAGT-3'(SEQ ID NO:2021)
5'-AAAUAUACUUAAAAAUUAAUAGUtt-3'(SEQ ID NO:1319)
3'-AUUUUAUAUGAAUUUUUAAUUAUCAAA-5'(SEQ ID NO:616)
KRAS-3848靶:5'-TAAAATATACTTAAAAATTAATAGTTT-3'(SEQ ID NO:2022)
5'-AAUAUACUUAAAAAUUAAUAGUUtt-3'(SEQ ID NO:1320)
3'-UUUUAUAUGAAUUUUUAAUUAUCAAAA-5'(SEQ ID NO:617)
KRAS-3849靶:5'-AAAATATACTTAAAAATTAATAGTTTT-3'(SEQ ID NO:2023)
5'-AUAUACUUAAAAAUUAAUAGUUUta-3'(SEQ ID NO:1321)
3'-UUUAUAUGAAUUUUUAAUUAUCAAAAU-5'(SEQ ID NO:618)
KRAS-3850靶:5'-AAATATACTTAAAAATTAATAGTTTTA-3'(SEQ ID NO:2024)
5'-UAUACUUAAAAAUUAAUAGUUUUat-3'(SEQ ID NO:1322)
3'-UUAUAUGAAUUUUUAAUUAUCAAAAUA-5'(SEQ ID NO:619)
KRAS-3851靶:5'-AATATACTTAAAAATTAATAGTTTTAT-3'(SEQ ID NO:2025)
5'-CUUAAAAAUUAAUAGUUUUAUCUgg-3'(SEQ ID NO:1323)
3'-AUGAAUUUUUAAUUAUCAAAAUAGACC-5'(SEQ ID NO:620)
KRAS-3855靶:5'-TACTTAAAAATTAATAGTTTTATCTGG-3'(SEQ ID NO:2026)
5'-AAAAUUAAUAGUUUUAUCUGGGUac-3'(SEQ ID NO:1324)
3'-AUUUUUAAUUAUCAAAAUAGACCCAUG-5'(SEQ ID NO:621)
KRAS-3859靶:5'-TAAAAATTAATAGTTTTATCTGGGTAC-3'(SEQ ID NO:2027)
5'-AAAUUAAUAGUUUUAUCUGGGUAca-3'(SEQ ID NO:1325)
3'-UUUUUAAUUAUCAAAAUAGACCCAUGU-5'(SEQ ID NO:622)
KRAS-3860靶:5'-AAAAATTAATAGTTTTATCTGGGTACA-3'(SEQ ID NO:2028)
5'-AAUUAAUAGUUUUAUCUGGGUACaa-3'(SEQ ID NO:1326)
3'-UUUUAAUUAUCAAAAUAGACCCAUGUU-5'(SEQ ID NO:623)
KRAS-3861靶:5'-AAAATTAATAGTTTTATCTGGGTACAA-3'(SEQ ID NO:2029)
5'-CUGGGUACAAAUAAACAGGUGCCtg-3'(SEQ ID NO:1327)
3'-UAGACCCAUGUUUAUUUGUCCACGGAC-5'(SEQ ID NO:624)
KRAS-3876靶:5'-ATCTGGGTACAAATAAACAGGTGCCTG-3'(SEQ ID NO:2030)
5'-CAAGGAAACUUCUAUGUAAAAAUca-3'(SEQ ID NO:1328)
3'-CUGUUCCUUUGAAGAUACAUUUUUAGU-5'(SEQ ID NO:625)
KRAS-3915靶:5'-GACAAGGAAACTTCTATGTAAAAATCA-3'(SEQ ID NO:2031)
5'-AAGGAAACUUCUAUGUAAAAAUCac-3'(SEQ ID NO:1329)
3'-UGUUCCUUUGAAGAUACAUUUUUAGUG-5'(SEQ ID NO:626)
KRAS-3916靶:5'-ACAAGGAAACTTCTATGTAAAAATCAC-3'(SEQ ID NO:2032)
5'-AGGAAACUUCUAUGUAAAAAUCAct-3'(SEQ ID NO:1330)
3'-GUUCCUUUGAAGAUACAUUUUUAGUGA-5'(SEQ ID NO:627)
KRAS-3917靶:5'-CAAGGAAACTTCTATGTAAAAATCACT-3'(SEQ ID NO:2033)
5'-CUAUGUAAAAAUCACUAUGAUUUct-3'(SEQ ID NO:1331)
3'-AAGAUACAUUUUUAGUGAUACUAAAGA-5'(SEQ ID NO:628)
KRAS-3926靶:5'-TTCTATGTAAAAATCACTATGATTTCT-3'(SEQ ID NO:2034)
5'-UAUGUAAAAAUCACUAUGAUUUCtg-3'(SEQ ID NO:1332)
3'-AGAUACAUUUUUAGUGAUACUAAAGAC-5'(SEQ ID NO:629)
KRAS-3927靶:5'-TCTATGTAAAAATCACTATGATTTCTG-3'(SEQ ID NO:2035)
5'-AUGUAAAAAUCACUAUGAUUUCUga-3'(SEQ ID NO:1333)
3'-GAUACAUUUUUAGUGAUACUAAAGACU-5'(SEQ ID NO:630)
KRAS-3928靶:5'-CTATGTAAAAATCACTATGATTTCTGA-3'(SEQ ID NO:2036)
5'-AAAAAUCACUAUGAUUUCUGAAUtg-3'(SEQ ID NO:1334)
3'-CAUUUUUAGUGAUACUAAAGACUUAAC-5'(SEQ ID NO:631)
KRAS-3932靶:5'-GTAAAAATCACTATGATTTCTGAATTG-3'(SEQ ID NO:2037)
5'-AAAAUCACUAUGAUUUCUGAAUUgc-3'(SEQ ID NO:1335)
3'-AUUUUUAGUGAUACUAAAGACUUAACG-5'(SEQ ID NO:632)
KRAS-3933靶:5'-TAAAAATCACTATGATTTCTGAATTGC-3'(SEQ ID NO:2038)
5'-AUGAUUUCUGAAUUGCUAUGUGAaa-3'(SEQ ID NO:1336)
3'-GAUACUAAAGACUUAACGAUACACUUU-5'(SEQ ID NO:633)
KRAS-3942靶:5'-CTATGATTTCTGAATTGCTATGTGAAA-3'(SEQ ID NO:2039)
5'-UGAUUUCUGAAUUGCUAUGUGAAac-3'(SEQ ID NO:1337)
3'-AUACUAAAGACUUAACGAUACACUUUG-5'(SEQ ID NO:634)
KRAS-3943靶:5'-TATGATTTCTGAATTGCTATGTGAAAC-3'(SEQ ID NO:2040)
5'-UGUGAAACUACAGAUCUUUGGAAca-3'(SEQ ID NO:1338)
3'-AUACACUUUGAUGUCUAGAAACCUUGU-5'(SEQ ID NO:635)
KRAS-3960靶:5'-TATGTGAAACTACAGATCTTTGGAACA-3'(SEQ ID NO:2041)
5'-GUGAAACUACAGAUCUUUGGAACac-3'(SEQ ID NO:1339)
3'-UACACUUUGAUGUCUAGAAACCUUGUG-5'(SEQ ID NO:636)
KRAS-3961靶:5'-ATGTGAAACTACAGATCTTTGGAACAC-3'(SEQ ID NO:2042)
5'-GGUGUUAAGACUUACACAGUACCtc-3'(SEQ ID NO:1340)
3'-UCCCACAAUUCUGAAUGUGUCAUGGAG-5'(SEQ ID NO:637)
KRAS-3997靶:5'-AGGGTGTTAAGACTTACACAGTACCTC-3'(SEQ ID NO:2043)
5'-UAGGCCUCUUGAAUUUUUGAUGUag-3'(SEQ ID NO:1341)
3'-AAAUCCGGAGAACUUAAAAACUACAUC-5'(SEQ ID NO:638)
KRAS-4084靶:5'-TTTAGGCCTCTTGAATTTTTGATGTAG-3'(SEQ ID NO:2044)
5'-UUGAAUUUUUGAUGUAGAUGGGCat-3'(SEQ ID NO:1342)
3'-AGAACUUAAAAACUACAUCUACCCGUA-5'(SEQ ID NO:639)
KRAS-4092靶:5'-TCTTGAATTTTTGATGTAGATGGGCAT-3'(SEQ ID NO:2045)
5'-UGAAUUUUUGAUGUAGAUGGGCAtt-3'(SEQ ID NO:1343)
3'-GAACUUAAAAACUACAUCUACCCGUAA-5'(SEQ ID NO:640)
KRAS-4093靶:5'-CTTGAATTTTTGATGTAGATGGGCATT-3'(SEQ ID NO:2046)
5'-GAUGGGCAUUUUUUUAAGGUAGUgg-3'(SEQ ID NO:1344)
3'-AUCUACCCGUAAAAAAAUUCCAUCACC-5'(SEQ ID NO:641)
KRAS-4108靶:5'-TAGATGGGCATTTTTTTAAGGTAGTGG-3'(SEQ ID NO:2047)
5'-CAUUUUUUUAAGGUAGUGGUUAAtt-3'(SEQ ID NO:1345)
3'-CCGUAAAAAAAUUCCAUCACCAAUUAA-5'(SEQ ID NO:642)
KRAS-4114靶:5'-GGCATTTTTTTAAGGTAGTGGTTAATT-3'(SEQ ID NO:2048)
5'-GUAGUGGUUAAUUACCUUUAUGUga-3'(SEQ ID NO:1346)
3'-UCCAUCACCAAUUAAUGGAAAUACACU-5'(SEQ ID NO:643)
KRAS-4126靶:5'-AGGTAGTGGTTAATTACCTTTATGTGA-3'(SEQ ID NO:2049)
5'-AGUGGUUAAUUACCUUUAUGUGAac-3'(SEQ ID NO:1347)
3'-CAUCACCAAUUAAUGGAAAUACACUUG-5'(SEQ ID NO:644)
KRAS-4128靶:5'-GTAGTGGTTAATTACCTTTATGTGAAC-3'(SEQ ID NO:2050)
5'-GUGGUUAAUUACCUUUAUGUGAAct-3'(SEQ ID NO:1348)
3'-AUCACCAAUUAAUGGAAAUACACUUGA-5'(SEQ ID NO:645)
KRAS-4129靶:5'-TAGTGGTTAATTACCTTTATGTGAACT-3'(SEQ ID NO:2051)
5'-UGGUUAAUUACCUUUAUGUGAACtt-3'(SEQ ID NO:1349)
3'-UCACCAAUUAAUGGAAAUACACUUGAA-5'(SEQ ID NO:646)
KRAS-4130靶:5'-AGTGGTTAATTACCTTTATGTGAACTT-3'(SEQ ID NO:2052)
5'-GGUUAAUUACCUUUAUGUGAACUtt-3'(SEQ ID NO:1350)
3'-CACCAAUUAAUGGAAAUACACUUGAAA-5'(SEQ ID NO:647)
KRAS-4131靶:5'-GTGGTTAATTACCTTTATGTGAACTTT-3'(SEQ ID NO:2053)
5'-CUUUAUGUGAACUUUGAAUGGUUta-3'(SEQ ID NO:1351)
3'-UGGAAAUACACUUGAAACUUACCAAAU-5'(SEQ ID NO:648)
KRAS-4141靶:5'-ACCTTTATGTGAACTTTGAATGGTTTA-3'(SEQ ID NO:2054)
5'-UGUGAACUUUGAAUGGUUUAACAaa-3'(SEQ ID NO:1352)
3'-AUACACUUGAAACUUACCAAAUUGUUU-5'(SEQ ID NO:649)
KRAS-4146靶:5'-TATGTGAACTTTGAATGGTTTAACAAA-3'(SEQ ID NO:2055)
5'-CUUUGAAUGGUUUAACAAAAGAUtt-3'(SEQ ID NO:1353)
3'-UUGAAACUUACCAAAUUGUUUUCUAAA-5'(SEQ ID NO:650)
KRAS-4152靶:5'-AACTTTGAATGGTTTAACAAAAGATTT-3'(SEQ ID NO:2056)
5'-GAAUGGUUUAACAAAAGAUUUGUtt-3'(SEQ ID NO:1354)
3'-AACUUACCAAAUUGUUUUCUAAACAAA-5'(SEQ ID NO:651)
KRAS-4156靶:5'-TTGAATGGTTTAACAAAAGATTTGTTT-3'(SEQ ID NO:2057)
5'-AAUGGUUUAACAAAAGAUUUGUUtt-3'(SEQ ID NO:1355)
3'-ACUUACCAAAUUGUUUUCUAAACAAAA-5'(SEQ ID NO:652)
KRAS-4157靶:5'-TGAATGGTTTAACAAAAGATTTGTTTT-3'(SEQ ID NO:2058)
5'-AUGGUUUAACAAAAGAUUUGUUUtt-3'(SEQ ID NO:1356)
3'-CUUACCAAAUUGUUUUCUAAACAAAAA-5'(SEQ ID NO:653)
KRAS-4158靶:5'-GAATGGTTTAACAAAAGATTTGTTTTT-3'(SEQ ID NO:2059)
5'-UGGUUUAACAAAAGAUUUGUUUUtg-3'(SEQ ID NO:1357)
3'-UUACCAAAUUGUUUUCUAAACAAAAAC-5'(SEQ ID NO:654)
KRAS-4159靶:5'-AATGGTTTAACAAAAGATTTGTTTTTG-3'(SEQ ID NO:2060)
5'-GGUUUAACAAAAGAUUUGUUUUUgt-3'(SEQ ID NO:1358)
3'-UACCAAAUUGUUUUCUAAACAAAAACA-5'(SEQ ID NO:655)
KRAS-4160靶:5'-ATGGTTTAACAAAAGATTTGTTTTTGT-3'(SEQ ID NO:2061)
5'-UUUAACAAAAGAUUUGUUUUUGUag-3'(SEQ ID NO:1359)
3'-CCAAAUUGUUUUCUAAACAAAAACAUC-5'(SEQ ID NO:656)
KRAS-4162靶:5'-GGTTTAACAAAAGATTTGTTTTTGTAG-3'(SEQ ID NO:2062)
5'-UUAACAAAAGAUUUGUUUUUGUAga-3'(SEQ ID NO:1360)
3'-CAAAUUGUUUUCUAAACAAAAACAUCU-5'(SEQ ID NO:657)
KRAS-4163靶:5'-GTTTAACAAAAGATTTGTTTTTGTAGA-3'(SEQ ID NO:2063)
5'-CAAAAGAUUUGUUUUUGUAGAGAtt-3'(SEQ ID NO:1361)
3'-UUGUUUUCUAAACAAAAACAUCUCUAA-5'(SEQ ID NO:658)
KRAS-4167靶:5'-AACAAAAGATTTGTTTTTGTAGAGATT-3'(SEQ ID NO:2064)
5'-AAAAGAUUUGUUUUUGUAGAGAUtt-3'(SEQ ID NO:1362)
3'-UGUUUUCUAAACAAAAACAUCUCUAAA-5'(SEQ ID NO:659)
KRAS-4168靶:5'-ACAAAAGATTTGTTTTTGTAGAGATTT-3'(SEQ ID NO:2065)
5'-AAAGAUUUGUUUUUGUAGAGAUUtt-3'(SEQ ID NO:1363)
3'-GUUUUCUAAACAAAAACAUCUCUAAAA-5'(SEQ ID NO:660)
KRAS-4169靶:5'-CAAAAGATTTGTTTTTGTAGAGATTTT-3'(SEQ ID NO:2066)
5'-AGAUUUGUUUUUGUAGAGAUUUUaa-3'(SEQ ID NO:1364)
3'-UUUCUAAACAAAAACAUCUCUAAAAUU-5'(SEQ ID NO:661)
KRAS-4171靶:5'-AAAGATTTGTTTTTGTAGAGATTTTAA-3'(SEQ ID NO:2067)
5'-GAUUUGUUUUUGUAGAGAUUUUAaa-3'(SEQ ID NO:1365)
3'-UUCUAAACAAAAACAUCUCUAAAAUUU-5'(SEQ ID NO:662)
KRAS-4172靶:5'-AAGATTTGTTTTTGTAGAGATTTTAAA-3'(SEQ ID NO:2068)
5'-AUUUGUUUUUGUAGAGAUUUUAAag-3'(SEQ ID NO:1366)
3'-UCUAAACAAAAACAUCUCUAAAAUUUC-5'(SEQ ID NO:663)
KRAS-4173靶:5'-AGATTTGTTTTTGTAGAGATTTTAAAG-3'(SEQ ID NO:2069)
5'-UUUGUUUUUGUAGAGAUUUUAAAgg-3'(SEQ ID NO:1367)
3'-CUAAACAAAAACAUCUCUAAAAUUUCC-5'(SEQ ID NO:664)
KRAS-4174靶:5'-GATTTGTTTTTGTAGAGATTTTAAAGG-3'(SEQ ID NO:2070)
5'-UUUGUAGAGAUUUUAAAGGGGGAga-3'(SEQ ID NO:1368)
3'-AAAAACAUCUCUAAAAUUUCCCCCUCU-5'(SEQ ID NO:665)
KRAS-4180靶:5'-TTTTTGTAGAGATTTTAAAGGGGGAGA-3'(SEQ ID NO:2071)
5'-GGGGGAGAAUUCUAGAAAUAAAUgt-3'(SEQ ID NO:1369)
3'-UUCCCCCUCUUAAGAUCUUUAUUUACA-5'(SEQ ID NO:666)
KRAS-4197靶:5'-AAGGGGGAGAATTCTAGAAATAAATGT-3'(SEQ ID NO:2072)
5'-GGGAGAAUUCUAGAAAUAAAUGUta-3'(SEQ ID NO:1370)
3'-CCCCCUCUUAAGAUCUUUAUUUACAAU-5'(SEQ ID NO:667)
KRAS-4199靶:5'-GGGGGAGAATTCTAGAAATAAATGTTA-3'(SEQ ID NO:2073)
5'-GGAGAAUUCUAGAAAUAAAUGUUac-3'(SEQ ID NO:1371)
3'-CCCCUCUUAAGAUCUUUAUUUACAAUG-5'(SEQ ID NO:668)
KRAS-4200靶:5'-GGGGAGAATTCTAGAAATAAATGTTAC-3'(SEQ ID NO:2074)
5'-GAGAAUUCUAGAAAUAAAUGUUAcc-3'(SEQ ID NO:1372)
3'-CCCUCUUAAGAUCUUUAUUUACAAUGG-5'(SEQ ID NO:669)
KRAS-4201靶:5'-GGGAGAATTCTAGAAATAAATGTTACC-3'(SEQ ID NO:2075)
5'-AGAAUUCUAGAAAUAAAUGUUACct-3'(SEQ ID NO:1373)
3'-CCUCUUAAGAUCUUUAUUUACAAUGGA-5'(SEQ ID NO:670)
KRAS-4202靶:5'-GGAGAATTCTAGAAATAAATGTTACCT-3'(SEQ ID NO:2076)
5'-GAAUUCUAGAAAUAAAUGUUACCta-3'(SEQ ID NO:1374)
3'-CUCUUAAGAUCUUUAUUUACAAUGGAU-5'(SEQ ID NO:671)
KRAS-4203靶:5'-GAGAATTCTAGAAATAAATGTTACCTA-3'(SEQ ID NO:2077)
5'-CUAGAAAUAAAUGUUACCUAAUUat-3'(SEQ ID NO:1375)
3'-AAGAUCUUUAUUUACAAUGGAUUAAUA-5'(SEQ ID NO:672)
KRAS-4208靶:5'-TTCTAGAAATAAATGTTACCTAATTAT-3'(SEQ ID NO:2078)
5'-UAGAAAUAAAUGUUACCUAAUUAtt-3'(SEQ ID NO:1376)
3'-AGAUCUUUAUUUACAAUGGAUUAAUAA-5'(SEQ ID NO:673)
KRAS-4209靶:5'-TCTAGAAATAAATGTTACCTAATTATT-3'(SEQ ID NO:2079)
5'-AGAAAUAAAUGUUACCUAAUUAUta-3'(SEQ ID NO:1377)
3'-GAUCUUUAUUUACAAUGGAUUAAUAAU-5'(SEQ ID NO:674)
KRAS-4210靶:5'-CTAGAAATAAATGTTACCTAATTATTA-3'(SEQ ID NO:2080)
5'-GAAAUAAAUGUUACCUAAUUAUUac-3'(SEQ ID NO:1378)
3'-AUCUUUAUUUACAAUGGAUUAAUAAUG-5'(SEQ ID NO:675)
KRAS-4211靶:5'-TAGAAATAAATGTTACCTAATTATTAC-3'(SEQ ID NO:2081)
5'-AAAUAAAUGUUACCUAAUUAUUAca-3'(SEQ ID NO:1379)
3'-UCUUUAUUUACAAUGGAUUAAUAAUGU-5'(SEQ ID NO:676)
KRAS-4212靶:5'-AGAAATAAATGTTACCTAATTATTACA-3'(SEQ ID NO:2082)
5'-AUAAAUGUUACCUAAUUAUUACAgc-3'(SEQ ID NO:1380)
3'-UUUAUUUACAAUGGAUUAAUAAUGUCG-5'(SEQ ID NO:677)
KRAS-4214靶:5'-AAATAAATGTTACCTAATTATTACAGC-3'(SEQ ID NO:2083)
5'-CUAAUUAUUACAGCCUUAAAGACaa-3'(SEQ ID NO:1381)
3'-UGGAUUAAUAAUGUCGGAAUUUCUGUU-5'(SEQ ID NO:678)
KRAS-4225靶:5'-ACCTAATTATTACAGCCTTAAAGACAA-3'(SEQ ID NO:2084)
5'-UAAUUAUUACAGCCUUAAAGACAaa-3'(SEQ ID NO:1382)
3'-GGAUUAAUAAUGUCGGAAUUUCUGUUU-5'(SEQ ID NO:679)
KRAS-4226靶:5'-CCTAATTATTACAGCCTTAAAGACAAA-3'(SEQ ID NO:2085)
5'-UUAAAGACAAAAAUCCUUGUUGAag-3'(SEQ ID NO:1383)
3'-GGAAUUUCUGUUUUUAGGAACAACUUC-5'(SEQ ID NO:680)
KRAS-4240靶:5'-CCTTAAAGACAAAAATCCTTGTTGAAG-3'(SEQ ID NO:2086)
5'-AAGACAAAAAUCCUUGUUGAAGUtt-3'(SEQ ID NO:1384)
3'-AUUUCUGUUUUUAGGAACAACUUCAAA-5'(SEQ ID NO:681)
KRAS-4243靶:5'-TAAAGACAAAAATCCTTGTTGAAGTTT-3'(SEQ ID NO:2087)
5'-CUUGUUGAAGUUUUUUUAAAAAAag-3'(SEQ ID NO:1385)
3'-AGGAACAACUUCAAAAAAAUUUUUUUC-5'(SEQ ID NO:682)
KRAS-4255靶:5'-TCCTTGTTGAAGTTTTTTTAAAAAAAG-3'(SEQ ID NO:2088)
5'-UUGUUGAAGUUUUUUUAAAAAAAgc-3'(SEQ ID NO:1386)
3'-GGAACAACUUCAAAAAAAUUUUUUUCG-5'(SEQ ID NO:683)
KRAS-4256靶:5'-CCTTGTTGAAGTTTTTTTAAAAAAAGC-3'(SEQ ID NO:2089)
5'-GUUGAAGUUUUUUUAAAAAAAGCta-3'(SEQ ID NO:1387)
3'-AACAACUUCAAAAAAAUUUUUUUCGAU-5'(SEQ ID NO:684)
KRAS-4258靶:5'-TTGTTGAAGTTTTTTTAAAAAAAGCTA-3'(SEQ ID NO:2090)
5'-UUGAAGUUUUUUUAAAAAAAGCUaa-3'(SEQ ID NO:1388)
3'-ACAACUUCAAAAAAAUUUUUUUCGAUU-5'(SEQ ID NO:685)
KRAS-4259靶:5'-TGTTGAAGTTTTTTTAAAAAAAGCTAA-3'(SEQ ID NO:2091)
5'-AGUUUUUUUAAAAAAAGCUAAAUta-3'(SEQ ID NO:1389)
3'-CUUCAAAAAAAUUUUUUUCGAUUUAAU-5'(SEQ ID NO:686)
KRAS-4263靶:5'-GAAGTTTTTTTAAAAAAAGCTAAATTA-3'(SEQ ID NO:2092)
5'-GUUUUUUUAAAAAAAGCUAAAUUac-3'(SEQ ID NO:1390)
3'-UUCAAAAAAAUUUUUUUCGAUUUAAUG-5'(SEQ ID NO:687)
KRAS-4264靶:5'-AAGTTTTTTTAAAAAAAGCTAAATTAC-3'(SEQ ID NO:2093)
5'-UUUUUUUAAAAAAAGCUAAAUUAca-3'(SEQ ID NO:1391)
3'-UCAAAAAAAUUUUUUUCGAUUUAAUGU-5'(SEQ ID NO:688)
KRAS-4265靶:5'-AGTTTTTTTAAAAAAAGCTAAATTACA-3'(SEQ ID NO:2094)
5'-UUUUUUAAAAAAAGCUAAAUUACat-3'(SEQ ID NO:1392)
3'-CAAAAAAAUUUUUUUCGAUUUAAUGUA-5'(SEQ ID NO:689)
KRAS-4266靶:5'-GTTTTTTTAAAAAAAGCTAAATTACAT-3'(SEQ ID NO:2095)
5'-UUUUUAAAAAAAGCUAAAUUACAta-3'(SEQ ID NO:1393)
3'-AAAAAAAUUUUUUUCGAUUUAAUGUAU-5'(SEQ ID NO:690)
KRAS-4267靶:5'-TTTTTTTAAAAAAAGCTAAATTACATA-3'(SEQ ID NO:2096)
5'-UAAAAAAAGCUAAAUUACAUAGAct-3'(SEQ ID NO:1394)
3'-AAAUUUUUUUCGAUUUAAUGUAUCUGA-5'(SEQ ID NO:691)
KRAS-4271靶:5'-TTTAAAAAAAGCTAAATTACATAGACT-3'(SEQ ID NO:2097)
5'-AAAAAAGCUAAAUUACAUAGACUta-3'(SEQ ID NO:1395)
3'-AUUUUUUUCGAUUUAAUGUAUCUGAAU-5'(SEQ ID NO:692)
KRAS-4273靶:5'-TAAAAAAAGCTAAATTACATAGACTTA-3'(SEQ ID NO:2098)
5'-UUAGGCAUUAACAUGUUUGUGGAag-3'(SEQ ID NO:1396)
3'-UGAAUCCGUAAUUGUACAAACACCUUC-5'(SEQ ID NO:693)
KRAS-4295靶:5'-ACTTAGGCATTAACATGTTTGTGGAAG-3'(SEQ ID NO:2099)
5'-UAGGCAUUAACAUGUUUGUGGAAga-3'(SEQ ID NO:1397)
3'-GAAUCCGUAAUUGUACAAACACCUUCU-5'(SEQ ID NO:694)
KRAS-4296靶:5'-CTTAGGCATTAACATGTTTGTGGAAGA-3'(SEQ ID NO:2100)
5'-CAGACGUAUAUUGUAUCAUUUGAgt-3'(SEQ ID NO:1398)
3'-UCGUCUGCAUAUAACAUAGUAAACUCA-5'(SEQ ID NO:695)
KRAS-4327靶:5'-AGCAGACGTATATTGTATCATTTGAGT-3'(SEQ ID NO:2101)
5'-CGUAUAUUGUAUCAUUUGAGUGAat-3'(SEQ ID NO:1399)
3'-CUGCAUAUAACAUAGUAAACUCACUUA-5'(SEQ ID NO:696)
KRAS-4331靶:5'-GACGTATATTGTATCATTTGAGTGAAT-3'(SEQ ID NO:2102)
5'-UAUAUUGUAUCAUUUGAGUGAAUgt-3'(SEQ ID NO:1400)
3'-GCAUAUAACAUAGUAAACUCACUUACA-5'(SEQ ID NO:697)
KRAS-4333靶:5'-CGTATATTGTATCATTTGAGTGAATGT-3'(SEQ ID NO:2103)
5'-AUUGUAUCAUUUGAGUGAAUGUUcc-3'(SEQ ID NO:1401)
3'-UAUAACAUAGUAAACUCACUUACAAGG-5'(SEQ ID NO:698)
KRAS-4336靶:5'-ATATTGTATCATTTGAGTGAATGTTCC-3'(SEQ ID NO:2104)
5'-UUGUAUCAUUUGAGUGAAUGUUCcc-3'(SEQ ID NO:1402)
3'-AUAACAUAGUAAACUCACUUACAAGGG-5'(SEQ ID NO:699)
KRAS-4337靶:5'-TATTGTATCATTTGAGTGAATGTTCCC-3'(SEQ ID NO:2105)
5'-UGUAUCAUUUGAGUGAAUGUUCCca-3'(SEQ ID NO:1403)
3'-UAACAUAGUAAACUCACUUACAAGGGU-5'(SEQ ID NO:700)
KRAS-4338靶:5'-ATTGTATCATTTGAGTGAATGTTCCCA-3'(SEQ ID NO:2106)
5'-AGGAAUUUAGAACCUAACUUUUAta-3'(SEQ ID NO:1404)
3'-UAUCCUUAAAUCUUGGAUUGAAAAUAU-5'(SEQ ID NO:701)
KRAS-4404靶:5'-ATAGGAATTTAGAACCTAACTTTTATA-3'(SEQ ID NO:2107)
5'-GGAAUUUAGAACCUAACUUUUAUag-3'(SEQ ID NO:1405)
3'-AUCCUUAAAUCUUGGAUUGAAAAUAUC-5'(SEQ ID NO:702)
KRAS-4405靶:5'-TAGGAATTTAGAACCTAACTTTTATAG-3'(SEQ ID NO:2108)
5'-UUUAGAACCUAACUUUUAUAGGUta-3'(SEQ ID NO:1406)
3'-UUAAAUCUUGGAUUGAAAAUAUCCAAU-5'(SEQ ID NO:703)
KRAS-4409靶:5'-AATTTAGAACCTAACTTTTATAGGTTA-3'(SEQ ID NO:2109)
5'-UUAGAACCUAACUUUUAUAGGUUat-3'(SEQ ID NO:1407)
3'-UAAAUCUUGGAUUGAAAAUAUCCAAUA-5'(SEQ ID NO:704)
KRAS-4410靶:5'-ATTTAGAACCTAACTTTTATAGGTTAT-3'(SEQ ID NO:2110)
5'-UAGAACCUAACUUUUAUAGGUUAtc-3'(SEQ ID NO:1408)
3'-AAAUCUUGGAUUGAAAAUAUCCAAUAG-5'(SEQ ID NO:705)
KRAS-4411靶:5'-TTTAGAACCTAACTTTTATAGGTTATC-3'(SEQ ID NO:2111)
5'-AGAACCUAACUUUUAUAGGUUAUca-3'(SEQ ID NO:1409)
3'-AAUCUUGGAUUGAAAAUAUCCAAUAGU-5'(SEQ ID NO:706)
KRAS-4412靶:5'-TTAGAACCTAACTTTTATAGGTTATCA-3'(SEQ ID NO:2112)
5'-UUAUAGGUUAUCAAAACUGUUGUca-3'(SEQ ID NO:1410)
3'-AAAAUAUCCAAUAGUUUUGACAACAGU-5'(SEQ ID NO:707)
KRAS-4424靶:5'-TTTTATAGGTTATCAAAACTGTTGTCA-3'(SEQ ID NO:2113)
5'-AUAGGUUAUCAAAACUGUUGUCAcc-3'(SEQ ID NO:1411)
3'-AAUAUCCAAUAGUUUUGACAACAGUGG-5'(SEQ ID NO:708)
KRAS-4426靶:5'-TTATAGGTTATCAAAACTGTTGTCACC-3'(SEQ ID NO:2114)
5'-UUUUGUCCUAAUAUAUACAUAGAaa-3'(SEQ ID NO:1412)
3'-UUAAAACAGGAUUAUAUAUGUAUCUUU-5'(SEQ ID NO:709)
KRAS-4460靶:5'-AATTTTGTCCTAATATATACATAGAAA-3'(SEQ ID NO:2115)
5'-UUUGUCCUAAUAUAUACAUAGAAac-3'(SEQ ID NO:1413)
3'-UAAAACAGGAUUAUAUAUGUAUCUUUG-5'(SEQ ID NO:710)
KRAS-4461靶:5'-ATTTTGTCCTAATATATACATAGAAAC-3'(SEQ ID NO:2116)
5'-UUGUCCUAAUAUAUACAUAGAAAct-3'(SEQ ID NO:1414)
3'-AAAACAGGAUUAUAUAUGUAUCUUUGA-5'(SEQ ID NO:711)
KRAS-4462靶:5'-TTTTGTCCTAATATATACATAGAAACT-3'(SEQ ID NO:2117)
5'-UAAUAUAUACAUAGAAACUUUGUgg-3'(SEQ ID NO:1415)
3'-GGAUUAUAUAUGUAUCUUUGAAACACC-5'(SEQ ID NO:712)
KRAS-4468靶:5'-CCTAATATATACATAGAAACTTTGTGG-3'(SEQ ID NO:2118)
5'-UAUACAUAGAAACUUUGUGGGGCat-3'(SEQ ID NO:1416)
3'-AUAUAUGUAUCUUUGAAACACCCCGUA-5'(SEQ ID NO:713)
KRAS-4473靶:5'-TATATACATAGAAACTTTGTGGGGCAT-3'(SEQ ID NO:2119)
5'-CAAGUUCAUCUCAUUUGUAUUCCat-3'(SEQ ID NO:1417)
3'-GUGUUCAAGUAGAGUAAACAUAAGGUA-5'(SEQ ID NO:714)
KRAS-4516靶:5'-CACAAGTTCATCTCATTTGTATTCCAT-3'(SEQ ID NO:2120)
5'-CAUUUGUAUUCCAUUGAUUUUUUtt-3'(SEQ ID NO:1418)
3'-GAGUAAACAUAAGGUAACUAAAAAAAA-5'(SEQ ID NO:715)
KRAS-4527靶:5'-CTCATTTGTATTCCATTGATTTTTTTT-3'(SEQ ID NO:2121)
5'-AUUUGUAUUCCAUUGAUUUUUUUtt-3'(SEQ ID NO:1419)
3'-AGUAAACAUAAGGUAACUAAAAAAAAA-5'(SEQ ID NO:716)
KRAS-4528靶:5'-TCATTTGTATTCCATTGATTTTTTTTT-3'(SEQ ID NO:2122)
5'-UUUGUAUUCCAUUGAUUUUUUUUtt-3'(SEQ ID NO:1420)
3'-GUAAACAUAAGGUAACUAAAAAAAAAA-5'(SEQ ID NO:717)
KRAS-4529靶:5'-CATTTGTATTCCATTGATTTTTTTTTT-3'(SEQ ID NO:2123)
5'-UUGUAUUCCAUUGAUUUUUUUUUtc-3'(SEQ ID NO:1421)
3'-UAAACAUAAGGUAACUAAAAAAAAAAG-5'(SEQ ID NO:718)
KRAS-4530靶:5'-ATTTGTATTCCATTGATTTTTTTTTTC-3'(SEQ ID NO:2124)
5'-UGUAUUCCAUUGAUUUUUUUUUUct-3'(SEQ ID NO:1422)
3'-AAACAUAAGGUAACUAAAAAAAAAAGA-5'(SEQ ID NO:719)
KRAS-4531靶:5'-TTTGTATTCCATTGATTTTTTTTTTCT-3'(SEQ ID NO:2125)
5'-GUAUUCCAUUGAUUUUUUUUUUCtt-3'(SEQ ID NO:1423)
3'-AACAUAAGGUAACUAAAAAAAAAAGAA-5'(SEQ ID NO:720)
KRAS-4532靶:5'-TTGTATTCCATTGATTTTTTTTTTCTT-3'(SEQ ID NO:2126)
5'-UAUUCCAUUGAUUUUUUUUUUCUtc-3'(SEQ ID NO:1424)
3'-ACAUAAGGUAACUAAAAAAAAAAGAAG-5'(SEQ ID NO:721)
KRAS-4533靶:5'-TGTATTCCATTGATTTTTTTTTTCTTC-3'(SEQ ID NO:2127)
5'-UUGAUUUUUUUUUUCUUCUAAACat-3'(SEQ ID NO:1425)
3'-GUAACUAAAAAAAAAAGAAGAUUUGUA-5'(SEQ ID NO:722)
KRAS-4540靶:5'-CATTGATTTTTTTTTTCTTCTAAACAT-3'(SEQ ID NO:2128)
5'-UGAUUUUUUUUUUCUUCUAAACAtt-3'(SEQ ID NO:1426)
3'-UAACUAAAAAAAAAAGAAGAUUUGUAA-5'(SEQ ID NO:723)
KRAS-4541靶:5'-ATTGATTTTTTTTTTCTTCTAAACATT-3'(SEQ ID NO:2129)
5'-UUUUUUUUUCUUCUAAACAUUUUtt-3'(SEQ ID NO:1427)
3'-UAAAAAAAAAAGAAGAUUUGUAAAAAA-5'(SEQ ID NO:724)
KRAS-4545靶:5'-ATTTTTTTTTTCTTCTAAACATTTTTT-3'(SEQ ID NO:2130)
5'-UUUUUUUUCUUCUAAACAUUUUUtc-3'(SEQ ID NO:1428)
3'-AAAAAAAAAAGAAGAUUUGUAAAAAAG-5'(SEQ ID NO:725)
KRAS-4546靶:5'-TTTTTTTTTTCTTCTAAACATTTTTTC-3'(SEQ ID NO:2131)
5'-UUUUUUUCUUCUAAACAUUUUUUct-3'(SEQ ID NO:1429)
3'-AAAAAAAAAGAAGAUUUGUAAAAAAGA-5'(SEQ ID NO:726)
KRAS-4547靶:5'-TTTTTTTTTCTTCTAAACATTTTTTCT-3'(SEQ ID NO:2132)
5'-UUUUUUCUUCUAAACAUUUUUUCtt-3'(SEQ ID NO:1430)
3'-AAAAAAAAGAAGAUUUGUAAAAAAGAA-5'(SEQ ID NO:727)
KRAS-4548靶:5'-TTTTTTTTCTTCTAAACATTTTTTCTT-3'(SEQ ID NO:2133)
5'-UUUUUCUUCUAAACAUUUUUUCUtc-3'(SEQ ID NO:1431)
3'-AAAAAAAGAAGAUUUGUAAAAAAGAAG-5'(SEQ ID NO:728)
KRAS-4549靶:5'-TTTTTTTCTTCTAAACATTTTTTCTTC-3'(SEQ ID NO:2134)
5'-CAUUUUUUCUUCAAACAGUAUAUaa-3'(SEQ ID NO:1432)
3'-UUGUAAAAAAGAAGUUUGUCAUAUAUU-5'(SEQ ID NO:729)
KRAS-4562靶:5'-AACATTTTTTCTTCAAACAGTATATAA-3'(SEQ ID NO:2135)
5'-AUUUUUUCUUCAAACAGUAUAUAac-3'(SEQ ID NO:1433)
3'-UGUAAAAAAGAAGUUUGUCAUAUAUUG-5'(SEQ ID NO:730)
KRAS-4563靶:5'-ACATTTTTTCTTCAAACAGTATATAAC-3'(SEQ ID NO:2136)
5'-UUUUUUCUUCAAACAGUAUAUAAct-3'(SEQ ID NO:1434)
3'-GUAAAAAAGAAGUUUGUCAUAUAUUGA-5'(SEQ ID NO:731)
KRAS-4564靶:5'-CATTTTTTCTTCAAACAGTATATAACT-3'(SEQ ID NO:2137)
5'-UUUUUCUUCAAACAGUAUAUAACtt-3'(SEQ ID NO:1435)
3'-UAAAAAAGAAGUUUGUCAUAUAUUGAA-5'(SEQ ID NO:732)
KRAS-4565靶:5'-ATTTTTTCTTCAAACAGTATATAACTT-3'(SEQ ID NO:2138)
5'-UUUUCUUCAAACAGUAUAUAACUtt-3'(SEQ ID NO:1436)
3'-AAAAAAGAAGUUUGUCAUAUAUUGAAA-5'(SEQ ID NO:733)
KRAS-4566靶:5'-TTTTTTCTTCAAACAGTATATAACTTT-3'(SEQ ID NO:2139)
5'-CAAACAGUAUAUAACUUUUUUUAgg-3'(SEQ ID NO:1437)
3'-AAGUUUGUCAUAUAUUGAAAAAAAUCC-5'(SEQ ID NO:734)
KRAS-4573靶:5'-TTCAAACAGTATATAACTTTTTTTAGG-3'(SEQ ID NO:2140)
5'-AGUAUAUAACUUUUUUUAGGGGAtt-3'(SEQ ID NO:1438)
3'-UGUCAUAUAUUGAAAAAAAUCCCCUAA-5'(SEQ ID NO:735)
KRAS-4578靶:5'-ACAGTATATAACTTTTTTTAGGGGATT-3'(SEQ ID NO:2141)
5'-GUAUAUAACUUUUUUUAGGGGAUtt-3'(SEQ ID NO:1439)
3'-GUCAUAUAUUGAAAAAAAUCCCCUAAA-5'(SEQ ID NO:736)
KRAS-4579靶:5'-CAGTATATAACTTTTTTTAGGGGATTT-3'(SEQ ID NO:2142)
5'-UAUAUAACUUUUUUUAGGGGAUUtt-3'(SEQ ID NO:1440)
3'-UCAUAUAUUGAAAAAAAUCCCCUAAAA-5'(SEQ ID NO:737)
KRAS-4580靶:5'-AGTATATAACTTTTTTTAGGGGATTTT-3'(SEQ ID NO:2143)
5'-AUAUAACUUUUUUUAGGGGAUUUtt-3'(SEQ ID NO:1441)
3'-CAUAUAUUGAAAAAAAUCCCCUAAAAA-5'(SEQ ID NO:738)
KRAS-4581靶:5'-GTATATAACTTTTTTTAGGGGATTTTT-3'(SEQ ID NO:2144)
5'-CUUUUUUUAGGGGAUUUUUUUUUag-3'(SEQ ID NO:1442)
3'-UUGAAAAAAAUCCCCUAAAAAAAAAUC-5'(SEQ ID NO:739)
KRAS-4587靶:5'-AACTTTTTTTAGGGGATTTTTTTTTAG-3'(SEQ ID NO:2145)
5'-UUUUUUUAGGGGAUUUUUUUUUAga-3'(SEQ ID NO:1443)
3'-UGAAAAAAAUCCCCUAAAAAAAAAUCU-5'(SEQ ID NO:740)
KRAS-4588靶:5'-ACTTTTTTTAGGGGATTTTTTTTTAGA-3'(SEQ ID NO:2146)
5'-GAUUUUUUUUUAGACAGCAAAAAct-3'(SEQ ID NO:1444)
3'-CCCUAAAAAAAAAUCUGUCGUUUUUGA-5'(SEQ ID NO:741)
KRAS-4599靶:5'-GGGATTTTTTTTTAGACAGCAAAAACT-3'(SEQ ID NO:2147)
5'-AUUUUUUUUUAGACAGCAAAAACta-3'(SEQ ID NO:1445)
3'-CCUAAAAAAAAAUCUGUCGUUUUUGAU-5'(SEQ ID NO:742)
KRAS-4600靶:5'-GGATTTTTTTTTAGACAGCAAAAACTA-3'(SEQ ID NO:2148)
5'-UUUUUUUUUAGACAGCAAAAACUat-3'(SEQ ID NO:1446)
3'-CUAAAAAAAAAUCUGUCGUUUUUGAUA-5'(SEQ ID NO:743)
KRAS-4601靶:5'-GATTTTTTTTTAGACAGCAAAAACTAT-3'(SEQ ID NO:2149)
5'-AAGAUUUCCAUUUGUCAAAAAGUaa-3'(SEQ ID NO:1447)
3'-ACUUCUAAAGGUAAACAGUUUUUCAUU-5'(SEQ ID NO:744)
KRAS-4629靶:5'-TGAAGATTTCCATTTGTCAAAAAGTAA-3'(SEQ ID NO:2150)
5'-AGAUUUCCAUUUGUCAAAAAGUAat-3'(SEQ ID NO:1448)
3'-CUUCUAAAGGUAAACAGUUUUUCAUUA-5'(SEQ ID NO:745)
KRAS-4630靶:5'-GAAGATTTCCATTTGTCAAAAAGTAAT-3'(SEQ ID NO:2151)
5'-GAUUUCCAUUUGUCAAAAAGUAAtg-3'(SEQ ID NO:1449)
3'-UUCUAAAGGUAAACAGUUUUUCAUUAC-5'(SEQ ID NO:746)
KRAS-4631靶:5'-AAGATTTCCATTTGTCAAAAAGTAATG-3'(SEQ ID NO:2152)
5'-AUUUCCAUUUGUCAAAAAGUAAUga-3'(SEQ ID NO:1450)
3'-UCUAAAGGUAAACAGUUUUUCAUUACU-5'(SEQ ID NO:747)
KRAS-4632靶:5'-AGATTTCCATTTGTCAAAAAGTAATGA-3'(SEQ ID NO:2153)
5'-CAUUUGUCAAAAAGUAAUGAUUUct-3'(SEQ ID NO:1451)
3'-AGGUAAACAGUUUUUCAUUACUAAAGA-5'(SEQ ID NO:748)
KRAS-4637靶:5'-TCCATTTGTCAAAAAGTAATGATTTCT-3'(SEQ ID NO:2154)
5'-AUUUGUCAAAAAGUAAUGAUUUCtt-3'(SEQ ID NO:1452)
3'-GGUAAACAGUUUUUCAUUACUAAAGAA-5'(SEQ ID NO:749)
KRAS-4638靶:5'-CCATTTGTCAAAAAGTAATGATTTCTT-3'(SEQ ID NO:2155)
5'-UUUGUCAAAAAGUAAUGAUUUCUtg-3'(SEQ ID NO:1453)
3'-GUAAACAGUUUUUCAUUACUAAAGAAC-5'(SEQ ID NO:750)
KRAS-4639靶:5'-CATTTGTCAAAAAGTAATGATTTCTTG-3'(SEQ ID NO:2156)
5'-CAAAAAGUAAUGAUUUCUUGAUAat-3'(SEQ ID NO:1454)
3'-CAGUUUUUCAUUACUAAAGAACUAUUA-5'(SEQ ID NO:751)
KRAS-4644靶:5'-GTCAAAAAGTAATGATTTCTTGATAAT-3'(SEQ ID NO:2157)
5'-AAAAAGUAAUGAUUUCUUGAUAAtt-3'(SEQ ID NO:1455)
3'-AGUUUUUCAUUACUAAAGAACUAUUAA-5'(SEQ ID NO:752)
KRAS-4645靶:5'-TCAAAAAGTAATGATTTCTTGATAATT-3'(SEQ ID NO:2158)
5'-AAAAGUAAUGAUUUCUUGAUAAUtg-3'(SEQ ID NO:1456)
3'-GUUUUUCAUUACUAAAGAACUAUUAAC-5'(SEQ ID NO:753)
KRAS-4646靶:5'-CAAAAAGTAATGATTTCTTGATAATTG-3'(SEQ ID NO:2159)
5'-AAAGUAAUGAUUUCUUGAUAAUUgt-3'(SEQ ID NO:1457)
3'-UUUUUCAUUACUAAAGAACUAUUAACA-5'(SEQ ID NO:754)
KRAS-4647靶:5'-AAAAAGTAATGATTTCTTGATAATTGT-3'(SEQ ID NO:2160)
5'-AGUAAUGAUUUCUUGAUAAUUGUgt-3'(SEQ ID NO:1458)
3'-UUUCAUUACUAAAGAACUAUUAACACA-5'(SEQ ID NO:755)
KRAS-4649靶:5'-AAAGTAATGATTTCTTGATAATTGTGT-3'(SEQ ID NO:2161)
5'-UAAUGAUUUCUUGAUAAUUGUGUag-3'(SEQ ID NO:1459)
3'-UCAUUACUAAAGAACUAUUAACACAUC-5'(SEQ ID NO:756)
KRAS-4651靶:5'-AGTAATGATTTCTTGATAATTGTGTAG-3'(SEQ ID NO:2162)
5'-AAUGAUUUCUUGAUAAUUGUGUAgt-3'(SEQ ID NO:1460)
3'-CAUUACUAAAGAACUAUUAACACAUCA-5'(SEQ ID NO:757)
KRAS-4652靶:5'-GTAATGATTTCTTGATAATTGTGTAGT-3'(SEQ ID NO:2163)
5'-UGAUUUCUUGAUAAUUGUGUAGUaa-3'(SEQ ID NO:1461)
3'-UUACUAAAGAACUAUUAACACAUCAUU-5'(SEQ ID NO:758)
KRAS-4654靶:5'-AATGATTTCTTGATAATTGTGTAGTAA-3'(SEQ ID NO:2164)
5'-GAUUUCUUGAUAAUUGUGUAGUAat-3'(SEQ ID NO:1462)
3'-UACUAAAGAACUAUUAACACAUCAUUA-5'(SEQ ID NO:759)
KRAS-4655靶:5'-ATGATTTCTTGATAATTGTGTAGTAAT-3'(SEQ ID NO:2165)
5'-CUUGAUAAUUGUGUAGUAAUGUUtt-3'(SEQ ID NO:1463)
3'-AAGAACUAUUAACACAUCAUUACAAAA-5'(SEQ ID NO:760)
KRAS-4660靶:5'-TTCTTGATAATTGTGTAGTAATGTTTT-3'(SEQ ID NO:2166)
5'-UUGAUAAUUGUGUAGUAAUGUUUtt-3'(SEQ ID NO:1464)
3'-AGAACUAUUAACACAUCAUUACAAAAA-5'(SEQ ID NO:761)
KRAS-4661靶:5'-TCTTGATAATTGTGTAGTAATGTTTTT-3'(SEQ ID NO:2167)
5'-UGAUAAUUGUGUAGUAAUGUUUUtt-3'(SEQ ID NO:1465)
3'-GAACUAUUAACACAUCAUUACAAAAAA-5'(SEQ ID NO:762)
KRAS-4662靶:5'-CTTGATAATTGTGTAGTAATGTTTTTT-3'(SEQ ID NO:2168)
5'-AUAAUUGUGUAGUAAUGUUUUUUag-3'(SEQ ID NO:1466)
3'-ACUAUUAACACAUCAUUACAAAAAAUC-5'(SEQ ID NO:763)
KRAS-4664靶:5'-TGATAATTGTGTAGTAATGTTTTTTAG-3'(SEQ ID NO:2169)
5'-AUUGUGUAGUAAUGUUUUUUAGAac-3'(SEQ ID NO:1467)
3'-AUUAACACAUCAUUACAAAAAAUCUUG-5'(SEQ ID NO:764)
KRAS-4667靶:5'-TAATTGTGTAGTAATGTTTTTTAGAAC-3'(SEQ ID NO:2170)
5'-UGUGUAGUAAUGUUUUUUAGAACcc-3'(SEQ ID NO:1468)
3'-UAACACAUCAUUACAAAAAAUCUUGGG-5'(SEQ ID NO:765)
KRAS-4669靶:5'-ATTGTGTAGTAATGTTTTTTAGAACCC-3'(SEQ ID NO:2171)
5'-GUGUAGUAAUGUUUUUUAGAACCca-3'(SEQ ID NO:1469)
3'-AACACAUCAUUACAAAAAAUCUUGGGU-5'(SEQ ID NO:766)
KRAS-4670靶:5'-TTGTGTAGTAATGTTTTTTAGAACCCA-3'(SEQ ID NO:2172)
5'-UUAAAGCUGAAUUUAUAUUUAGUaa-3'(SEQ ID NO:1470)
3'-GGAAUUUCGACUUAAAUAUAAAUCAUU-5'(SEQ ID NO:767)
KRAS-4704靶:5'-CCTTAAAGCTGAATTTATATTTAGTAA-3'(SEQ ID NO:2173)
5'-AAAGCUGAAUUUAUAUUUAGUAAct-3'(SEQ ID NO:1471)
3'-AAUUUCGACUUAAAUAUAAAUCAUUGA-5'(SEQ ID NO:768)
KRAS-4706靶:5'-TTAAAGCTGAATTTATATTTAGTAACT-3'(SEQ ID NO:2174)
5'-UUUAUAUUUAGUAACUUCUGUGUta-3'(SEQ ID NO:1472)
3'-UUAAAUAUAAAUCAUUGAAGACACAAU-5'(SEQ ID NO:769)
KRAS-4715靶:5'-AATTTATATTTAGTAACTTCTGTGTTA-3'(SEQ ID NO:2175)
5'-UUAUAUUUAGUAACUUCUGUGUUaa-3'(SEQ ID NO:1473)
3'-UAAAUAUAAAUCAUUGAAGACACAAUU-5'(SEQ ID NO:770)
KRAS-4716靶:5'-ATTTATATTTAGTAACTTCTGTGTTAA-3'(SEQ ID NO:2176)
5'-UAUAUUUAGUAACUUCUGUGUUAat-3'(SEQ ID NO:1474)
3'-AAAUAUAAAUCAUUGAAGACACAAUUA-5'(SEQ ID NO:771)
KRAS-4717靶:5'-TTTATATTTAGTAACTTCTGTGTTAAT-3'(SEQ ID NO:2177)
5'-UUAGUAACUUCUGUGUUAAUACUgg-3'(SEQ ID NO:1475)
3'-UAAAUCAUUGAAGACACAAUUAUGACC-5'(SEQ ID NO:772)
KRAS-4722靶:5'-ATTTAGTAACTTCTGTGTTAATACTGG-3'(SEQ ID NO:2178)
5'-UGAAUAGCUGUCAUAAAAUGAAAct-3'(SEQ ID NO:1476)
3'-UGACUUAUCGACAGUAUUUUACUUUGA-5'(SEQ ID NO:773)
KRAS-4773靶:5'-ACTGAATAGCTGTCATAAAATGAAACT-3'(SEQ ID NO:2179)
5'-GAAUAGCUGUCAUAAAAUGAAACtt-3'(SEQ ID NO:1477)
3'-GACUUAUCGACAGUAUUUUACUUUGAA-5'(SEQ ID NO:774)
KRAS-4774靶:5'-CTGAATAGCTGTCATAAAATGAAACTT-3'(SEQ ID NO:2180)
5'-AAAUGAAACUUUCUUUCUAAAGAaa-3'(SEQ ID NO:1478)
3'-AUUUUACUUUGAAAGAAAGAUUUCUUU-5'(SEQ ID NO:775)
KRAS-4788靶:5'-TAAAATGAAACTTTCTTTCTAAAGAAA-3'(SEQ ID NO:2181)
5'-AAUGAAACUUUCUUUCUAAAGAAag-3'(SEQ ID NO:1479)
3'-UUUUACUUUGAAAGAAAGAUUUCUUUC-5'(SEQ ID NO:776)
KRAS-4789靶:5'-AAAATGAAACTTTCTTTCTAAAGAAAG-3'(SEQ ID NO:2182)
5'-AUGAAACUUUCUUUCUAAAGAAAga-3'(SEQ ID NO:1480)
3'-UUUACUUUGAAAGAAAGAUUUCUUUCU-5'(SEQ ID NO:777)
KRAS-4790靶:5'-AAATGAAACTTTCTTTCTAAAGAAAGA-3'(SEQ ID NO:2183)
5'-GAAACUUUCUUUCUAAAGAAAGAta-3'(SEQ ID NO:1481)
3'-UACUUUGAAAGAAAGAUUUCUUUCUAU-5'(SEQ ID NO:778)
KRAS-4792靶:5'-ATGAAACTTTCTTTCTAAAGAAAGATA-3'(SEQ ID NO:2184)
5'-CUUUCUUUCUAAAGAAAGAUACUca-3'(SEQ ID NO:1482)
3'-UUGAAAGAAAGAUUUCUUUCUAUGAGU-5'(SEQ ID NO:779)
KRAS-4796靶:5'-AACTTTCTTTCTAAAGAAAGATACTCA-3'(SEQ ID NO:2185)
5'-CAUGAGUUCUUGAAGAAUAGUCAta-3'(SEQ ID NO:1483)
3'-GUGUACUCAAGAACUUCUUAUCAGUAU-5'(SEQ ID NO:780)
KRAS-4821靶:5'-CACATGAGTTCTTGAAGAATAGTCATA-3'(SEQ ID NO:2186)
5'-UUGAAGAAUAGUCAUAACUAGAUta-3'(SEQ ID NO:1484)
3'-AGAACUUCUUAUCAGUAUUGAUCUAAU-5'(SEQ ID NO:781)
KRAS-4830靶:5'-TCTTGAAGAATAGTCATAACTAGATTA-3'(SEQ ID NO:2187)
5'-UGAAGAAUAGUCAUAACUAGAUUaa-3'(SEQ ID NO:1485)
3'-GAACUUCUUAUCAGUAUUGAUCUAAUU-5'(SEQ ID NO:782)
KRAS-4831靶:5'-CTTGAAGAATAGTCATAACTAGATTAA-3'(SEQ ID NO:2188)
5'-GAAGAAUAGUCAUAACUAGAUUAag-3'(SEQ ID NO:1486)
3'-AACUUCUUAUCAGUAUUGAUCUAAUUC-5'(SEQ ID NO:783)
KRAS-4832靶:5'-TTGAAGAATAGTCATAACTAGATTAAG-3'(SEQ ID NO:2189)
5'-GAAUAGUCAUAACUAGAUUAAGAtc-3'(SEQ ID NO:1487)
3'-UUCUUAUCAGUAUUGAUCUAAUUCUAG-5'(SEQ ID NO:784)
KRAS-4835靶:5'-AAGAATAGTCATAACTAGATTAAGATC-3'(SEQ ID NO:2190)
5'-AAUAGUCAUAACUAGAUUAAGAUct-3'(SEQ ID NO:1488)
3'-UCUUAUCAGUAUUGAUCUAAUUCUAGA-5'(SEQ ID NO:785)
KRAS-4836靶:5'-AGAATAGTCATAACTAGATTAAGATCT-3'(SEQ ID NO:2191)
5'-AUAGUCAUAACUAGAUUAAGAUCtg-3'(SEQ ID NO:1489)
3'-CUUAUCAGUAUUGAUCUAAUUCUAGAC-5'(SEQ ID NO:786)
KRAS-4837靶:5'-GAATAGTCATAACTAGATTAAGATCTG-3'(SEQ ID NO:2192)
5'-UAGUCAUAACUAGAUUAAGAUCUgt-3'(SEQ ID NO:1490)
3'-UUAUCAGUAUUGAUCUAAUUCUAGACA-5'(SEQ ID NO:787)
KRAS-4838靶:5'-AATAGTCATAACTAGATTAAGATCTGT-3'(SEQ ID NO:2193)
5'-CAUAACUAGAUUAAGAUCUGUGUtt-3'(SEQ ID NO:1491)
3'-CAGUAUUGAUCUAAUUCUAGACACAAA-5'(SEQ ID NO:788)
KRAS-4842靶:5'-GTCATAACTAGATTAAGATCTGTGTTT-3'(SEQ ID NO:2194)
5'-UAGAUUAAGAUCUGUGUUUUAGUtt-3'(SEQ ID NO:1492)
3'-UGAUCUAAUUCUAGACACAAAAUCAAA-5'(SEQ ID NO:789)
KRAS-4848靶:5'-ACTAGATTAAGATCTGTGTTTTAGTTT-3'(SEQ ID NO:2195)
5'-GAUUAAGAUCUGUGUUUUAGUUUaa-3'(SEQ ID NO:1493)
3'-AUCUAAUUCUAGACACAAAAUCAAAUU-5'(SEQ ID NO:790)
KRAS-4850靶:5'-TAGATTAAGATCTGTGTTTTAGTTTAA-3'(SEQ ID NO:2196)
5'-AUUAAGAUCUGUGUUUUAGUUUAat-3'(SEQ ID NO:1494)
3'-UCUAAUUCUAGACACAAAAUCAAAUUA-5'(SEQ ID NO:791)
KRAS-4851靶:5'-AGATTAAGATCTGTGTTTTAGTTTAAT-3'(SEQ ID NO:2197)
5'-UAAGAUCUGUGUUUUAGUUUAAUag-3'(SEQ ID NO:1495)
3'-UAAUUCUAGACACAAAAUCAAAUUAUC-5'(SEQ ID NO:792)
KRAS-4853靶:5'-ATTAAGATCTGTGTTTTAGTTTAATAG-3'(SEQ ID NO:2198)
5'-UGUGUUUUAGUUUAAUAGUUUGAag-3'(SEQ ID NO:1496)
3'-AGACACAAAAUCAAAUUAUCAAACUUC-5'(SEQ ID NO:793)
KRAS-4860靶:5'-TCTGTGTTTTAGTTTAATAGTTTGAAG-3'(SEQ ID NO:2199)
5'-GUGUUUUAGUUUAAUAGUUUGAAgt-3'(SEQ ID NO:1497)
3'-GACACAAAAUCAAAUUAUCAAACUUCA-5'(SEQ ID NO:794)
KRAS-4861靶:5'-CTGTGTTTTAGTTTAATAGTTTGAAGT-3'(SEQ ID NO:2200)
5'-GUUUUAGUUUAAUAGUUUGAAGUgc-3'(SEQ ID NO:1498)
3'-CACAAAAUCAAAUUAUCAAACUUCACG-5'(SEQ ID NO:795)
KRAS-4863靶:5'-GTGTTTTAGTTTAATAGTTTGAAGTGC-3'(SEQ ID NO:2201)
5'-UUUAGUUUAAUAGUUUGAAGUGCct-3'(SEQ ID NO:1499)
3'-CAAAAUCAAAUUAUCAAACUUCACGGA-5'(SEQ ID NO:796)
KRAS-4865靶:5'-GTTTTAGTTTAATAGTTTGAAGTGCCT-3'(SEQ ID NO:2202)
5'-UUAGUUUAAUAGUUUGAAGUGCCtg-3'(SEQ ID NO:1500)
3'-AAAAUCAAAUUAUCAAACUUCACGGAC-5'(SEQ ID NO:797)
KRAS-4866靶:5'-TTTTAGTTTAATAGTTTGAAGTGCCTG-3'(SEQ ID NO:2203)
5'-UUGGGAUAAUGAUAGGUAAUUUAga-3'(SEQ ID NO:1501)
3'-CAAACCCUAUUACUAUCCAUUAAAUCU-5'(SEQ ID NO:798)
KRAS-4892靶:5'-GTTTGGGATAATGATAGGTAATTTAGA-3'(SEQ ID NO:2204)
5'-GGGAUAAUGAUAGGUAAUUUAGAtg-3'(SEQ ID NO:1502)
3'-AACCCUAUUACUAUCCAUUAAAUCUAC-5'(SEQ ID NO:799)
KRAS-4894靶:5'-TTGGGATAATGATAGGTAATTTAGATG-3'(SEQ ID NO:2205)
5'-AUAAUGAUAGGUAAUUUAGAUGAat-3'(SEQ ID NO:1503)
3'-CCUAUUACUAUCCAUUAAAUCUACUUA-5'(SEQ ID NO:800)
KRAS-4897靶:5'-GGATAATGATAGGTAATTTAGATGAAT-3'(SEQ ID NO:2206)
5'-UAAUGAUAGGUAAUUUAGAUGAAtt-3'(SEQ ID NO:1504)
3'-CUAUUACUAUCCAUUAAAUCUACUUAA-5'(SEQ ID NO:801)
KRAS-4898靶:5'-GATAATGATAGGTAATTTAGATGAATT-3'(SEQ ID NO:2207)
5'-UGAUAGGUAAUUUAGAUGAAUUUag-3'(SEQ ID NO:1505)
3'-UUACUAUCCAUUAAAUCUACUUAAAUC-5'(SEQ ID NO:802)
KRAS-4901靶:5'-AATGATAGGTAATTTAGATGAATTTAG-3'(SEQ ID NO:2208)
5'-GAUAGGUAAUUUAGAUGAAUUUAgg-3'(SEQ ID NO:1506)
3'-UACUAUCCAUUAAAUCUACUUAAAUCC-5'(SEQ ID NO:803)
KRAS-4902靶:5'-ATGATAGGTAATTTAGATGAATTTAGG-3'(SEQ ID NO:2209)
5'-GUAAUUUAGAUGAAUUUAGGGGAaa-3'(SEQ ID NO:1507)
3'-UCCAUUAAAUCUACUUAAAUCCCCUUU-5'(SEQ ID NO:804)
KRAS-4907靶:5'-AGGTAATTTAGATGAATTTAGGGGAAA-3'(SEQ ID NO:2210)
5'-AAUUUAGAUGAAUUUAGGGGAAAaa-3'(SEQ ID NO:1508)
3'-CAUUAAAUCUACUUAAAUCCCCUUUUU-5'(SEQ ID NO:805)
KRAS-4909靶:5'-GTAATTTAGATGAATTTAGGGGAAAAA-3'(SEQ ID NO:2211)
5'-AUGAAUUUAGGGGAAAAAAAAGUta-3'(SEQ ID NO:1509)
3'-UCUACUUAAAUCCCCUUUUUUUUCAAU-5'(SEQ ID NO:806)
KRAS-4916靶:5'-AGATGAATTTAGGGGAAAAAAAAGTTA-3'(SEQ ID NO:2212)
5'-UGAAUUUAGGGGAAAAAAAAGUUat-3'(SEQ ID NO:1510)
3'-CUACUUAAAUCCCCUUUUUUUUCAAUA-5'(SEQ ID NO:807)
KRAS-4917靶:5'-GATGAATTTAGGGGAAAAAAAAGTTAT-3'(SEQ ID NO:2213)
5'-GAAAAAAAAGUUAUCUGCAGAUAtg-3'(SEQ ID NO:1511)
3'-CCCUUUUUUUUCAAUAGACGUCUAUAC-5'(SEQ ID NO:808)
KRAS-4928靶:5'-GGGAAAAAAAAGTTATCTGCAGATATG-3'(SEQ ID NO:2214)
5'-AAAAAAAAGUUAUCUGCAGAUAUgt-3'(SEQ ID NO:1512)
3'-CCUUUUUUUUCAAUAGACGUCUAUACA-5'(SEQ ID NO:809)
KRAS-4929靶:5'-GGAAAAAAAAGTTATCTGCAGATATGT-3'(SEQ ID NO:2215)
5'-AAAGUUAUCUGCAGAUAUGUUGAgg-3'(SEQ ID NO:1513)
3'-UUUUUCAAUAGACGUCUAUACAACUCC-5'(SEQ ID NO:810)
KRAS-4934靶:5'-AAAAAGTTATCTGCAGATATGTTGAGG-3'(SEQ ID NO:2216)
5'-CUUGUGUUUUCAUGUUGAAAAUAct-3'(SEQ ID NO:1514)
3'-CAGAACACAAAAGUACAACUUUUAUGA-5'(SEQ ID NO:811)
KRAS-5035靶:5'-GTCTTGTGTTTTCATGTTGAAAATACT-3'(SEQ ID NO:2217)
5'-UUGUGUUUUCAUGUUGAAAAUACtt-3'(SEQ ID NO:1515)
3'-AGAACACAAAAGUACAACUUUUAUGAA-5'(SEQ ID NO:812)
KRAS-5036靶:5'-TCTTGTGTTTTCATGTTGAAAATACTT-3'(SEQ ID NO:2218)
5'-UGUGUUUUCAUGUUGAAAAUACUtt-3'(SEQ ID NO:1516)
3'-GAACACAAAAGUACAACUUUUAUGAAA-5'(SEQ ID NO:813)
KRAS-5037靶:5'-CTTGTGTTTTCATGTTGAAAATACTTT-3'(SEQ ID NO:2219)
5'-UGUUGAAAAUACUUUUGCAUUUUtc-3'(SEQ ID NO:1517)
3'-GUACAACUUUUAUGAAAACGUAAAAAG-5'(SEQ ID NO:814)
KRAS-5047靶:5'-CATGTTGAAAATACTTTTGCATTTTTC-3'(SEQ ID NO:2220)
5'-GUUGAAAAUACUUUUGCAUUUUUcc-3'(SEQ ID NO:1518)
3'-UACAACUUUUAUGAAAACGUAAAAAGG-5'(SEQ ID NO:815)
KRAS-5048靶:5'-ATGTTGAAAATACTTTTGCATTTTTCC-3'(SEQ ID NO:2221)
5'-UUGAAAAUACUUUUGCAUUUUUCct-3'(SEQ ID NO:1519)
3'-ACAACUUUUAUGAAAACGUAAAAAGGA-5'(SEQ ID NO:816)
KRAS-5049靶:5'-TGTTGAAAATACTTTTGCATTTTTCCT-3'(SEQ ID NO:2222)
5'-UGAAAAUACUUUUGCAUUUUUCCtt-3'(SEQ ID NO:1520)
3'-CAACUUUUAUGAAAACGUAAAAAGGAA-5'(SEQ ID NO:817)
KRAS-5050靶:5'-GTTGAAAATACTTTTGCATTTTTCCTT-3'(SEQ ID NO:2223)
5'-UUUGCAUUUUUCCUUUGAGUGCCaa-3'(SEQ ID NO:1521)
3'-GAAAACGUAAAAAGGAAACUCACGGUU-5'(SEQ ID NO:818)
KRAS-5060靶:5'-CTTTTGCATTTTTCCTTTGAGTGCCAA-3'(SEQ ID NO:2224)
5'-AGUGCCAAUUUCUUACUAGUACUat-3'(SEQ ID NO:1522)
3'-ACUCACGGUUAAAGAAUGAUCAUGAUA-5'(SEQ ID NO:819)
KRAS-5077靶:5'-TGAGTGCCAATTTCTTACTAGTACTAT-3'(SEQ ID NO:2225)
5'-CAAUUUCUUACUAGUACUAUUUCtt-3'(SEQ ID NO:1523)
3'-CGGUUAAAGAAUGAUCAUGAUAAAGAA-5'(SEQ ID NO:820)
KRAS-5082靶:5'-GCCAATTTCTTACTAGTACTATTTCTT-3'(SEQ ID NO:2226)
5'-AAUUUCUUACUAGUACUAUUUCUta-3'(SEQ ID NO:1524)
3'-GGUUAAAGAAUGAUCAUGAUAAAGAAU-5'(SEQ ID NO:821)
KRAS-5083靶:5'-CCAATTTCTTACTAGTACTATTTCTTA-3'(SEQ ID NO:2227)
5'-CUAGUACUAUUUCUUAAUGUAACat-3'(SEQ ID NO:1525)
3'-AUGAUCAUGAUAAAGAAUUACAUUGUA-5'(SEQ ID NO:822)
KRAS-5092靶:5'-TACTAGTACTATTTCTTAATGTAACAT-3'(SEQ ID NO:2228)
5'-UAGUACUAUUUCUUAAUGUAACAtg-3'(SEQ ID NO:1526)
3'-UGAUCAUGAUAAAGAAUUACAUUGUAC-5'(SEQ ID NO:823)
KRAS-5093靶:5'-ACTAGTACTATTTCTTAATGTAACATG-3'(SEQ ID NO:2229)
5'-CUAUUUCUUAAUGUAACAUGUUUac-3'(SEQ ID NO:1527)
3'-AUGAUAAAGAAUUACAUUGUACAAAUG-5'(SEQ ID NO:824)
KRAS-5098靶:5'-TACTATTTCTTAATGTAACATGTTTAC-3'(SEQ ID NO:2230)
5'-UAUUUCUUAAUGUAACAUGUUUAcc-3'(SEQ ID NO:1528)
3'-UGAUAAAGAAUUACAUUGUACAAAUGG-5'(SEQ ID NO:825)
KRAS-5099靶:5'-ACTATTTCTTAATGTAACATGTTTACC-3'(SEQ ID NO:2231)
5'-AUUUCUUAAUGUAACAUGUUUACct-3'(SEQ ID NO:1529)
3'-GAUAAAGAAUUACAUUGUACAAAUGGA-5'(SEQ ID NO:826)
KRAS-5100靶:5'-CTATTTCTTAATGTAACATGTTTACCT-3'(SEQ ID NO:2232)
5'-AAUGUAACAUGUUUACCUGGAAUgt-3'(SEQ ID NO:1530)
3'-AAUUACAUUGUACAAAUGGACCUUACA-5'(SEQ ID NO:827)
KRAS-5107靶:5'-TTAATGTAACATGTTTACCTGGAATGT-3'(SEQ ID NO:2233)
5'-UGGAAUGUAUUUUAACUAUUUUUgt-3'(SEQ ID NO:1531)
3'-GGACCUUACAUAAAAUUGAUAAAAACA-5'(SEQ ID NO:828)
KRAS-5124靶:5'-CCTGGAATGTATTTTAACTATTTTTGT-3'(SEQ ID NO:2234)
5'-GAAUGUAUUUUAACUAUUUUUGUat-3'(SEQ ID NO:1532)
3'-ACCUUACAUAAAAUUGAUAAAAACAUA-5'(SEQ ID NO:829)
KRAS-5126靶:5'-TGGAATGTATTTTAACTATTTTTGTAT-3'(SEQ ID NO:2235)
5'-AAUGUAUUUUAACUAUUUUUGUAta-3'(SEQ ID NO:1533)
3'-CCUUACAUAAAAUUGAUAAAAACAUAU-5'(SEQ ID NO:830)
KRAS-5127靶:5'-GGAATGTATTTTAACTATTTTTGTATA-3'(SEQ ID NO:2236)
5'-AUGUAUUUUAACUAUUUUUGUAUag-3'(SEQ ID NO:1534)
3'-CUUACAUAAAAUUGAUAAAAACAUAUC-5'(SEQ ID NO:831)
KRAS-5128靶:5'-GAATGTATTTTAACTATTTTTGTATAG-3'(SEQ ID NO:2237)
5'-UGUAUUUUAACUAUUUUUGUAUAgt-3'(SEQ ID NO:1535)
3'-UUACAUAAAAUUGAUAAAAACAUAUCA-5'(SEQ ID NO:832)
KRAS-5129靶:5'-AATGTATTTTAACTATTTTTGTATAGT-3'(SEQ ID NO:2238)
5'-UAUUUUAACUAUUUUUGUAUAGUgt-3'(SEQ ID NO:1536)
3'-ACAUAAAAUUGAUAAAAACAUAUCACA-5'(SEQ ID NO:833)
KRAS-5131靶:5'-TGTATTTTAACTATTTTTGTATAGTGT-3'(SEQ ID NO:2239)
5'-UUUUAACUAUUUUUGUAUAGUGUaa-3'(SEQ ID NO:1537)
3'-AUAAAAUUGAUAAAAACAUAUCACAUU-5'(SEQ ID NO:834)
KRAS-5133靶:5'-TATTTTAACTATTTTTGTATAGTGTAA-3'(SEQ ID NO:2240)
5'-UUUAACUAUUUUUGUAUAGUGUAaa-3'(SEQ ID NO:1538)
3'-UAAAAUUGAUAAAAACAUAUCACAUUU-5'(SEQ ID NO:835)
KRAS-5134靶:5'-ATTTTAACTATTTTTGTATAGTGTAAA-3'(SEQ ID NO:2241)
5'-UUAACUAUUUUUGUAUAGUGUAAac-3'(SEQ ID NO:1539)
3'-AAAAUUGAUAAAAACAUAUCACAUUUG-5'(SEQ ID NO:836)
KRAS-5135靶:5'-TTTTAACTATTTTTGTATAGTGTAAAC-3'(SEQ ID NO:2242)
5'-UUUUUGUAUAGUGUAAACUGAAAca-3'(SEQ ID NO:1540)
3'-AUAAAAACAUAUCACAUUUGACUUUGU-5'(SEQ ID NO:837)
KRAS-5142靶:5'-TATTTTTGTATAGTGTAAACTGAAACA-3'(SEQ ID NO:2243)
5'-UUUUGUAUAGUGUAAACUGAAACat-3'(SEQ ID NO:1541)
3'-UAAAAACAUAUCACAUUUGACUUUGUA-5'(SEQ ID NO:838)
KRAS-5143靶:5'-ATTTTTGTATAGTGTAAACTGAAACAT-3'(SEQ ID NO:2244)
5'-UUUGUAUAGUGUAAACUGAAACAtg-3'(SEQ ID NO:1542)
3'-AAAAACAUAUCACAUUUGACUUUGUAC-5'(SEQ ID NO:839)
KRAS-5144靶:5'-TTTTTGTATAGTGTAAACTGAAACATG-3'(SEQ ID NO:2245)
5'-CUGAAACAUGCACAUUUUGUACAtt-3'(SEQ ID NO:1543)
3'-UUGACUUUGUACGUGUAAAACAUGUAA-5'(SEQ ID NO:840)
KRAS-5159靶:5'-AACTGAAACATGCACATTTTGTACATT-3'(SEQ ID NO:2246)
5'-CAUGCACAUUUUGUACAUUGUGCtt-3'(SEQ ID NO:1544)
3'-UUGUACGUGUAAAACAUGUAACACGAA-5'(SEQ ID NO:841)
KRAS-5165靶:5'-AACATGCACATTTTGTACATTGTGCTT-3'(SEQ ID NO:2247)
5'-CAGUUGUUUUCCAUCAUUUGGUUgc-3'(SEQ ID NO:1545)
3'-AGGUCAACAAAAGGUAGUAAACCAACG-5'(SEQ ID NO:842)
KRAS-5218靶:5'-TCCAGTTGTTTTCCATCATTTGGTTGC-3'(SEQ ID NO:2248)
5'-GUUGUUUUCCAUCAUUUGGUUGCgc-3'(SEQ ID NO:1546)
3'-GUCAACAAAAGGUAGUAAACCAACGCG-5'(SEQ ID NO:843)
KRAS-5220靶:5'-CAGTTGTTTTCCATCATTTGGTTGCGC-3'(SEQ ID NO:2249)
5'-GUUGGUCAUAUCAAACAUUAAAAat-3'(SEQ ID NO:1547)
3'-UACAACCAGUAUAGUUUGUAAUUUUUA-5'(SEQ ID NO:844)
KRAS-5257靶:5'-ATGTTGGTCATATCAAACATTAAAAAT-3'(SEQ ID NO:2250)
5'-UUGGUCAUAUCAAACAUUAAAAAtg-3'(SEQ ID NO:1548)
3'-ACAACCAGUAUAGUUUGUAAUUUUUAC-5'(SEQ ID NO:845)
KRAS-5258靶:5'-TGTTGGTCATATCAAACATTAAAAATG-3'(SEQ ID NO:2251)
5'-UGGUCAUAUCAAACAUUAAAAAUga-3'(SEQ ID NO:1549)
3'-CAACCAGUAUAGUUUGUAAUUUUUACU-5'(SEQ ID NO:846)
KRAS-5259靶:5'-GTTGGTCATATCAAACATTAAAAATGA-3'(SEQ ID NO:2252)
5'-CAUAUCAAACAUUAAAAAUGACCac-3'(SEQ ID NO:1550)
3'-CAGUAUAGUUUGUAAUUUUUACUGGUG-5'(SEQ ID NO:847)
KRAS-5263靶:5'-GTCATATCAAACATTAAAAATGACCAC-3'(SEQ ID NO:2253)
5'-AAUGACCACUCUUUUAAUUGAAAtt-3'(SEQ ID NO:1551)
3'-UUUUACUGGUGAGAAAAUUAACUUUAA-5'(SEQ ID NO:848)
KRAS-5279靶:5'-AAAATGACCACTCTTTTAATTGAAATT-3'(SEQ ID NO:2254)
5'-AUGACCACUCUUUUAAUUGAAAUta-3'(SEQ ID NO:1552)
3'-UUUACUGGUGAGAAAAUUAACUUUAAU-5'(SEQ ID NO:849)
KRAS-5280靶:5'-AAATGACCACTCTTTTAATTGAAATTA-3'(SEQ ID NO:2255)
5'-CUUUUAAUUGAAAUUAACUUUUAaa-3'(SEQ ID NO:1553)
3'-GAGAAAAUUAACUUUAAUUGAAAAUUU-5'(SEQ ID NO:850)
KRAS-5289靶:5'-CTCTTTTAATTGAAATTAACTTTTAAA-3'(SEQ ID NO:2256)
5'-UUUUAAUUGAAAUUAACUUUUAAat-3'(SEQ ID NO:1554)
3'-AGAAAAUUAACUUUAAUUGAAAAUUUA-5'(SEQ ID NO:851)
KRAS-5290靶:5'-TCTTTTAATTGAAATTAACTTTTAAAT-3'(SEQ ID NO:2257)
5'-UUAAUUGAAAUUAACUUUUAAAUgt-3'(SEQ ID NO:1555)
3'-AAAAUUAACUUUAAUUGAAAAUUUACA-5'(SEQ ID NO:852)
KRAS-5292靶:5'-TTTTAATTGAAATTAACTTTTAAATGT-3'(SEQ ID NO:2258)
5'-AAUUGAAAUUAACUUUUAAAUGUtt-3'(SEQ ID NO:1556)
3'-AAUUAACUUUAAUUGAAAAUUUACAAA-5'(SEQ ID NO:853)
KRAS-5294靶:5'-TTAATTGAAATTAACTTTTAAATGTTT-3'(SEQ ID NO:2259)
5'-AUUGAAAUUAACUUUUAAAUGUUta-3'(SEQ ID NO:1557)
3'-AUUAACUUUAAUUGAAAAUUUACAAAU-5'(SEQ ID NO:854)
KRAS-5295靶:5'-TAATTGAAATTAACTTTTAAATGTTTA-3'(SEQ ID NO:2260)
5'-UUGAAAUUAACUUUUAAAUGUUUat-3'(SEQ ID NO:1558)
3'-UUAACUUUAAUUGAAAAUUUACAAAUA-5'(SEQ ID NO:855)
KRAS-5296靶:5'-AATTGAAATTAACTTTTAAATGTTTAT-3'(SEQ ID NO:2261)
5'-UGAAAUUAACUUUUAAAUGUUUAta-3'(SEQ ID NO:1559)
3'-UAACUUUAAUUGAAAAUUUACAAAUAU-5'(SEQ ID NO:856)
KRAS-5297靶:5'-ATTGAAATTAACTTTTAAATGTTTATA-3'(SEQ ID NO:2262)
5'-GAAAUUAACUUUUAAAUGUUUAUag-3'(SEQ ID NO:1560)
3'-AACUUUAAUUGAAAAUUUACAAAUAUC-5'(SEQ ID NO:857)
KRAS-5298靶:5'-TTGAAATTAACTTTTAAATGTTTATAG-3'(SEQ ID NO:2263)
5'-AAAUUAACUUUUAAAUGUUUAUAgg-3'(SEQ ID NO:1561)
3'-ACUUUAAUUGAAAAUUUACAAAUAUCC-5'(SEQ ID NO:858)
KRAS-5299靶:5'-TGAAATTAACTTTTAAATGTTTATAGG-3'(SEQ ID NO:2264)
5'-UUAACUUUUAAAUGUUUAUAGGAgt-3'(SEQ ID NO:1562)
3'-UUAAUUGAAAAUUUACAAAUAUCCUCA-5'(SEQ ID NO:859)
KRAS-5302靶:5'-AATTAACTTTTAAATGTTTATAGGAGT-3'(SEQ ID NO:2265)
5'-CUUUUAAAUGUUUAUAGGAGUAUgt-3'(SEQ ID NO:1563)
3'-UUGAAAAUUUACAAAUAUCCUCAUACA-5'(SEQ ID NO:860)
KRAS-5306靶:5'-AACTTTTAAATGTTTATAGGAGTATGT-3'(SEQ ID NO:2266)
5'-UAAAUGUUUAUAGGAGUAUGUGCtg-3'(SEQ ID NO:1564)
3'-AAAUUUACAAAUAUCCUCAUACACGAC-5'(SEQ ID NO:861)
KRAS-5310靶:5'-TTTAAATGTTTATAGGAGTATGTGCTG-3'(SEQ ID NO:2267)
5'-AAAUGUUUAUAGGAGUAUGUGCUgt-3'(SEQ ID NO:1565)
3'-AAUUUACAAAUAUCCUCAUACACGACA-5'(SEQ ID NO:862)
KRAS-5311靶:5'-TTAAATGTTTATAGGAGTATGTGCTGT-3'(SEQ ID NO:2268)
5'-UGUGAAGUGAUCUAAAAUUUGUAat-3'(SEQ ID NO:1566)
3'-CGACACUUCACUAGAUUUUAAACAUUA-5'(SEQ ID NO:863)
KRAS-5333靶:5'-GCTGTGAAGTGATCTAAAATTTGTAAT-3'(SEQ ID NO:2269)
5'-UGAAGUGAUCUAAAAUUUGUAAUat-3'(SEQ ID NO:1567)
3'-ACACUUCACUAGAUUUUAAACAUUAUA-5'(SEQ ID NO:864)
KRAS-5335靶:5'-TGTGAAGTGATCTAAAATTTGTAATAT-3'(SEQ ID NO:2270)
5'-GAAGUGAUCUAAAAUUUGUAAUAtt-3'(SEQ ID NO:1568)
3'-CACUUCACUAGAUUUUAAACAUUAUAA-5'(SEQ ID NO:865)
KRAS-5336靶:5'-GTGAAGTGATCTAAAATTTGTAATATT-3'(SEQ ID NO:2271)
5'-AAGUGAUCUAAAAUUUGUAAUAUtt-3'(SEQ ID NO:1569)
3'-ACUUCACUAGAUUUUAAACAUUAUAAA-5'(SEQ ID NO:866)
KRAS-5337靶:5'-TGAAGTGATCTAAAATTTGTAATATTT-3'(SEQ ID NO:2272)
5'-AGUGAUCUAAAAUUUGUAAUAUUtt-3'(SEQ ID NO:1570)
3'-CUUCACUAGAUUUUAAACAUUAUAAAA-5'(SEQ ID NO:867)
KRAS-5338靶:5'-GAAGTGATCTAAAATTTGTAATATTTT-3'(SEQ ID NO:2273)
5'-GUGAUCUAAAAUUUGUAAUAUUUtt-3'(SEQ ID NO:1571)
3'-UUCACUAGAUUUUAAACAUUAUAAAAA-5'(SEQ ID NO:868)
KRAS-5339靶:5'-AAGTGATCTAAAATTTGTAATATTTTT-3'(SEQ ID NO:2274)
5'-UGAUCUAAAAUUUGUAAUAUUUUtg-3'(SEQ ID NO:1572)
3'-UCACUAGAUUUUAAACAUUAUAAAAAC-5'(SEQ ID NO:869)
KRAS-5340靶:5'-AGTGATCTAAAATTTGTAATATTTTTG-3'(SEQ ID NO:2275)
5'-CUAAAAUUUGUAAUAUUUUUGUCat-3'(SEQ ID NO:1573)
3'-UAGAUUUUAAACAUUAUAAAAACAGUA-5'(SEQ ID NO:870)
KRAS-5344靶:5'-ATCTAAAATTTGTAATATTTTTGTCAT-3'(SEQ ID NO:2276)
5'-UAAAAUUUGUAAUAUUUUUGUCAtg-3'(SEQ ID NO:1574)
3'-AGAUUUUAAACAUUAUAAAAACAGUAC-5'(SEQ ID NO:871)
KRAS-5345靶:5'-TCTAAAATTTGTAATATTTTTGTCATG-3'(SEQ ID NO:2277)
5'-AUUUGUAAUAUUUUUGUCAUGAAct-3'(SEQ ID NO:1575)
3'-UUUAAACAUUAUAAAAACAGUACUUGA-5'(SEQ ID NO:872)
KRAS-5349靶:5'-AAATTTGTAATATTTTTGTCATGAACT-3'(SEQ ID NO:2278)
5'-UUUGUAAUAUUUUUGUCAUGAACtg-3'(SEQ ID NO:1576)
3'-UUAAACAUUAUAAAAACAGUACUUGAC-5'(SEQ ID NO:873)
KRAS-5350靶:5'-AATTTGTAATATTTTTGTCATGAACTG-3'(SEQ ID NO:2279)
5'-UUGUAAUAUUUUUGUCAUGAACUgt-3'(SEQ ID NO:1577)
3'-UAAACAUUAUAAAAACAGUACUUGACA-5'(SEQ ID NO:874)
KRAS-5351靶:5'-ATTTGTAATATTTTTGTCATGAACTGT-3'(SEQ ID NO:2280)
5'-AAUAUUUUUGUCAUGAACUGUACta-3'(SEQ ID NO:1578)
3'-CAUUAUAAAAACAGUACUUGACAUGAU-5'(SEQ ID NO:875)
KRAS-5355靶:5'-GTAATATTTTTGTCATGAACTGTACTA-3'(SEQ ID NO:2281)
5'-AUAUUUUUGUCAUGAACUGUACUac-3'(SEQ ID NO:1579)
3'-AUUAUAAAAACAGUACUUGACAUGAUG-5'(SEQ ID NO:876)
KRAS-5356靶:5'-TAATATTTTTGTCATGAACTGTACTAC-3'(SEQ ID NO:2282)
5'-CUGUACUACUCCUAAUUAUUGUAat-3'(SEQ ID NO:1580)
3'-UUGACAUGAUGAGGAUUAAUAACAUUA-5'(SEQ ID NO:877)
KRAS-5372靶:5'-AACTGTACTACTCCTAATTATTGTAAT-3'(SEQ ID NO:2283)
5'-UGUACUACUCCUAAUUAUUGUAAtg-3'(SEQ ID NO:1581)
3'-UGACAUGAUGAGGAUUAAUAACAUUAC-5'(SEQ ID NO:878)
KRAS-5373靶:5'-ACTGTACTACTCCTAATTATTGTAATG-3'(SEQ ID NO:2284)
5'-CUAAUUAUUGUAAUGUAAUAAAAat-3'(SEQ ID NO:1582)
3'-AGGAUUAAUAACAUUACAUUAUUUUUA-5'(SEQ ID NO:879)
KRAS-5383靶:5'-TCCTAATTATTGTAATGTAATAAAAAT-3'(SEQ ID NO:2285)
5'-UAAUUAUUGUAAUGUAAUAAAAAta-3'(SEQ ID NO:1583)
3'-GGAUUAAUAACAUUACAUUAUUUUUAU-5'(SEQ ID NO:880)
KRAS-5384靶:5'-CCTAATTATTGTAATGTAATAAAAATA-3'(SEQ ID NO:2286)
5'-AUUAUUGUAAUGUAAUAAAAAUAgt-3'(SEQ ID NO:1584)
3'-AUUAAUAACAUUACAUUAUUUUUAUCA-5'(SEQ ID NO:881)
KRAS-5386靶:5'-TAATTATTGTAATGTAATAAAAATAGT-3'(SEQ ID NO:2287)
5'-UAUUGUAAUGUAAUAAAAAUAGUta-3'(SEQ ID NO:1585)
3'-UAAUAACAUUACAUUAUUUUUAUCAAU-5'(SEQ ID NO:882)
KRAS-5388靶:5'-ATTATTGTAATGTAATAAAAATAGTTA-3'(SEQ ID NO:2288)
5'-AUUGUAAUGUAAUAAAAAUAGUUac-3'(SEQ ID NO:1586)
3'-AAUAACAUUACAUUAUUUUUAUCAAUG-5'(SEQ ID NO:883)
KRAS-5389靶:5'-TTATTGTAATGTAATAAAAATAGTTAC-3'(SEQ ID NO:2289)
5'-UGUAAUGUAAUAAAAAUAGUUACag-3'(SEQ ID NO:1587)
3'-UAACAUUACAUUAUUUUUAUCAAUGUC-5'(SEQ ID NO:884)
KRAS-5391靶:5'-ATTGTAATGTAATAAAAATAGTTACAG-3'(SEQ ID NO:2290)
5'-GUAAUGUAAUAAAAAUAGUUACAgt-3'(SEQ ID NO:1588)
3'-AACAUUACAUUAUUUUUAUCAAUGUCA-5'(SEQ ID NO:885)
KRAS-5392靶:5'-TTGTAATGTAATAAAAATAGTTACAGT-3'(SEQ ID NO:2291)
5'-UGUAAUAAAAAUAGUUACAGUGAca-3'(SEQ ID NO:1589)
3'-UUACAUUAUUUUUAUCAAUGUCACUGU-5'(SEQ ID NO:886)
KRAS-5396靶:5'-AATGTAATAAAAATAGTTACAGTGACA-3'(SEQ ID NO:2292)
5'-GUAAUAAAAAUAGUUACAGUGACaa-3'(SEQ ID NO:1590)
3'-UACAUUAUUUUUAUCAAUGUCACUGUU-5'(SEQ ID NO:887)
KRAS-5397靶:5'-ATGTAATAAAAATAGTTACAGTGACAA-3'(SEQ ID NO:2293)
5'-UAAUAAAAAUAGUUACAGUGACAaa-3'(SEQ ID NO:1591)
3'-ACAUUAUUUUUAUCAAUGUCACUGUUU-5'(SEQ ID NO:888)
KRAS-5398靶:5'-TGTAATAAAAATAGTTACAGTGACAAA-3'(SEQ ID NO:2294)
5'-AUAGUUACAGUGACAAAAAAAAAaa-3'(SEQ ID NO:1592)
3'-UUUAUCAAUGUCACUGUUUUUUUUUUU-5'(SEQ ID NO:889)
KRAS-5406靶:5'-AAATAGTTACAGTGACAAAAAAAAAAA-3'(SEQ ID NO:2295)
5'-UAGUUACAGUGACAAAAAAAAAAaa-3'(SEQ ID NO:1593)
3'-UUAUCAAUGUCACUGUUUUUUUUUUUU-5'(SEQ ID NO:890)
KRAS-5407靶:5'-AATAGTTACAGTGACAAAAAAAAAAAA-3'(SEQ ID NO:2296)
5'-GUUACAGUGACAAAAAAAAAAAAaa-3'(SEQ ID NO:1594)
3'-AUCAAUGUCACUGUUUUUUUUUUUUUU-5'(SEQ ID NO:891)
KRAS-5409靶:5'-TAGTTACAGTGACAAAAAAAAAAAAAA-3'(SEQ ID NO:2297)
表5:其它优选的抗KRAS不对称DsiRNA试剂结构
5'-UGCUGAAAAUGACUGAAUAUAAAct-3'(SEQ ID NO:3001)
3'-GGACGACUUUUACUGACUUAUAUUUGA-5'(SEQ ID NO:2298)
KRAS-172靶:5'-CCTGCTGAAAATGACTGAATATAAACT-3'(SEQ ID NO:3704)
5'-AAAUGACUGAAUAUAAACUUGUGgt-3'(SEQ ID NO:3002)
3'-CUUUUACUGACUUAUAUUUGAACACCA-5'(SEQ ID NO:2299)
KRAS-178靶:5'-GAAAATGACTGAATATAAACTTGTGGT-3'(SEQ ID NO:3705)
5'-GACUGAAUAUAAACUUGUGGUAGtt-3'(SEQ ID NO:3003)
3'-UACUGACUUAUAUUUGAACACCAUCAA-5'(SEQ ID NO:2300)
KRAS-182靶:5'-ATGACTGAATATAAACTTGTGGTAGTT-3'(SEQ ID NO:3706)
5'-AGCUAAUUCAGAAUCAUUUUGUGga-3'(SEQ ID NO:3004)
3'-UGUCGAUUAAGUCUUAGUAAAACACCU-5'(SEQ ID NO:2301)
KRAS-244靶:5'-ACAGCTAATTCAGAATCATTTTGTGGA-3'(SEQ ID NO:3707)
5'-ACGAAUAUGAUCCAACAAUAGAGga-3'(SEQ ID NO:3005)
3'-CCUGCUUAUACUAGGUUGUUAUCUCCU-5'(SEQ ID NO:2302)
KRAS-268靶:5'-GGACGAATATGATCCAACAATAGAGGA-3'(SEQ ID NO:3708)
5'-AGCAAGUAGUAAUUGAUGGAGAAac-3'(SEQ ID NO:3006)
3'-CUUCGUUCAUCAUUAACUACCUCUUUG-5'(SEQ ID NO:2303)
KRAS-304靶:5'-GAAGCAAGTAGTAATTGATGGAGAAAC-3'(SEQ ID NO:3709)
5'-GGAGGGCUUUCUUUGUGUAUUUGcc-3'(SEQ ID NO:3007)
3'-CCCCUCCCGAAAGAAACACAUAAACGG-5'(SEQ ID NO:2304)
KRAS-404靶:5'-GGGGAGGGCTTTCTTTGTGTATTTGCC-3'(SEQ ID NO:3710)
5'-UCUUUGUGUAUUUGCCAUAAAUAat-3'(SEQ ID NO:3008)
3'-AAAGAAACACAUAAACGGUAUUUAUUA-5'(SEQ ID NO:2305)
KRAS-413靶:5'-TTTCTTTGTGTATTTGCCATAAATAAT-3'(SEQ ID NO:3711)
5'-CUUUGUGUAUUUGCCAUAAAUAAta-3'(SEQ ID NO:3009)
3'-AAGAAACACAUAAACGGUAUUUAUUAU-5'(SEQ ID NO:2306)
KRAS-414靶:5'-TTCTTTGTGTATTTGCCATAAATAATA-3'(SEQ ID NO:3712)
5'-UUUGUGUAUUUGCCAUAAAUAAUac-3'(SEQ ID NO:3010)
3'-AGAAACACAUAAACGGUAUUUAUUAUG-5'(SEQ ID NO:2307)
KRAS-415靶:5'-TCTTTGTGTATTTGCCATAAATAATAC-3'(SEQ ID NO:3713)
5'-UUGUGUAUUUGCCAUAAAUAAUAct-3'(SEQ ID NO:3011)
3'-GAAACACAUAAACGGUAUUUAUUAUGA-5'(SEQ ID NO:2308)
KRAS-416靶:5'-CTTTGTGTATTTGCCATAAATAATACT-3'(SEQ ID NO:3714)
5'-GUAUUUGCCAUAAAUAAUACUAAat-3'(SEQ ID NO:3012)
3'-CACAUAAACGGUAUUUAUUAUGAUUUA-5'(SEQ ID NO:2309)
KRAS-420靶:5'-GTGTATTTGCCATAAATAATACTAAAT-3'(SEQ ID NO:3715)
5'-UAUUUGCCAUAAAUAAUACUAAAtc-3'(SEQ ID NO:3013)
3'-ACAUAAACGGUAUUUAUUAUGAUUUAG-5'(SEQ ID NO:2310)
KRAS-421靶:5'-TGTATTTGCCATAAATAATACTAAATC-3'(SEQ ID NO:3716)
5'-CCAUAAAUAAUACUAAAUCAUUUga-3'(SEQ ID NO:3014)
3'-ACGGUAUUUAUUAUGAUUUAGUAAACU-5'(SEQ ID NO:2311)
KRAS-427靶:5'-TGCCATAAATAATACTAAATCATTTGA-3'(SEQ ID NO:3717)
5'-CAUAAAUAAUACUAAAUCAUUUGaa-3'(SEQ ID NO:3015)
3'-CGGUAUUUAUUAUGAUUUAGUAAACUU-5'(SEQ ID NO:2312)
KRAS-428靶:5'-GCCATAAATAATACTAAATCATTTGAA-3'(SEQ ID NO:3718)
5'-UAAAUAAUACUAAAUCAUUUGAAga-3'(SEQ ID NO:3016)
3'-GUAUUUAUUAUGAUUUAGUAAACUUCU-5'(SEQ ID NO:2313)
KRAS-430靶:5'-CATAAATAATACTAAATCATTTGAAGA-3'(SEQ ID NO:3719)
5'-AAAUAAUACUAAAUCAUUUGAAGat-3'(SEQ ID NO:3017)
3'-UAUUUAUUAUGAUUUAGUAAACUUCUA-5'(SEQ ID NO:2314)
KRAS-431靶:5'-ATAAATAATACTAAATCATTTGAAGAT-3'(SEQ ID NO:3720)
5'-AAUAAUACUAAAUCAUUUGAAGAta-3'(SEQ ID NO:3018)
3'-AUUUAUUAUGAUUUAGUAAACUUCUAU-5'(SEQ ID NO:2315)
KRAS-432靶:5'-TAAATAATACTAAATCATTTGAAGATA-3'(SEQ ID NO:3721)
5'-AUAAUACUAAAUCAUUUGAAGAUat-3'(SEQ ID NO:3019)
3'-UUUAUUAUGAUUUAGUAAACUUCUAUA-5'(SEQ ID NO:2316)
KRAS-433靶:5'-AAATAATACTAAATCATTTGAAGATAT-3'(SEQ ID NO:3722)
5'-AUUUGAAGAUAUUCACCAUUAUAga-3'(SEQ ID NO:3020)
3'-AGUAAACUUCUAUAAGUGGUAAUAUCU-5'(SEQ ID NO:2317)
KRAS-446靶:5'-TCATTTGAAGATATTCACCATTATAGA-3'(SEQ ID NO:3723)
5'-UUGAAGAUAUUCACCAUUAUAGAga-3'(SEQ ID NO:3021)
3'-UAAACUUCUAUAAGUGGUAAUAUCUCU-5'(SEQ ID NO:2318)
KRAS-448靶:5'-ATTTGAAGATATTCACCATTATAGAGA-3'(SEQ ID NO:3724)
5'-UGAAGAUAUUCACCAUUAUAGAGaa-3'(SEQ ID NO:3022)
3'-AAACUUCUAUAAGUGGUAAUAUCUCUU-5'(SEQ ID NO:2319)
KRAS-449靶:5'-TTTGAAGATATTCACCATTATAGAGAA-3'(SEQ ID NO:3725)
5'-GAAGAUAUUCACCAUUAUAGAGAac-3'(SEQ ID NO:3023)
3'-AACUUCUAUAAGUGGUAAUAUCUCUUG-5'(SEQ ID NO:2320)
KRAS-450靶:5'-TTGAAGATATTCACCATTATAGAGAAC-3'(SEQ ID NO:3726)
5'-AAGAUAUUCACCAUUAUAGAGAAca-3'(SEQ ID NO:3024)
3'-ACUUCUAUAAGUGGUAAUAUCUCUUGU-5'(SEQ ID NO:2321)
KRAS-451靶:5'-TGAAGATATTCACCATTATAGAGAACA-3'(SEQ ID NO:3727)
5'-CCAUUAUAGAGAACAAAUUAAAAga-3'(SEQ ID NO:3025)
3'-GUGGUAAUAUCUCUUGUUUAAUUUUCU-5'(SEQ ID NO:2322)
KRAS-461靶:5'-CACCATTATAGAGAACAAATTAAAAGA-3'(SEQ ID NO:3728)
5'-AUUAUAGAGAACAAAUUAAAAGAgt-3'(SEQ ID NO:3026)
3'-GGUAAUAUCUCUUGUUUAAUUUUCUCA-5'(SEQ ID NO:2323)
KRAS-463靶:5'-CCATTATAGAGAACAAATTAAAAGAGT-3'(SEQ ID NO:3729)
5'-UUAUAGAGAACAAAUUAAAAGAGtt-3'(SEQ ID NO:3027)
3'-GUAAUAUCUCUUGUUUAAUUUUCUCAA-5'(SEQ ID NO:2324)
KRAS-464靶:5'-CATTATAGAGAACAAATTAAAAGAGTT-3'(SEQ ID NO:3730)
5'-UAUAGAGAACAAAUUAAAAGAGUta-3'(SEQ ID NO:3028)
3'-UAAUAUCUCUUGUUUAAUUUUCUCAAU-5'(SEQ ID NO:2325)
KRAS-465靶:5'-ATTATAGAGAACAAATTAAAAGAGTTA-3'(SEQ ID NO:3731)
5'-AUAGAGAACAAAUUAAAAGAGUUaa-3'(SEQ ID NO:3029)
3'-AAUAUCUCUUGUUUAAUUUUCUCAAUU-5'(SEQ ID NO:2326)
KRAS-466靶:5'-TTATAGAGAACAAATTAAAAGAGTTAA-3'(SEQ ID NO:3732)
5'-CUAGUAGGAAAUAAAUGUGAUUUgc-3'(SEQ ID NO:3030)
3'-AGGAUCAUCCUUUAUUUACACUAAACG-5'(SEQ ID NO:2327)
KRAS-516靶:5'-TCCTAGTAGGAAATAAATGTGATTTGC-3'(SEQ ID NO:3733)
5'-UAGUAGGAAAUAAAUGUGAUUUGcc-3'(SEQ ID NO:3031)
3'-GGAUCAUCCUUUAUUUACACUAAACGG-5'(SEQ ID NO:2328)
KRAS-517靶:5'-CCTAGTAGGAAATAAATGTGATTTGCC-3'(SEQ ID NO:3734)
5'-AAGAAGUUAUGGAAUUCCUUUUAtt-3'(SEQ ID NO:3032)
3'-CGUUCUUCAAUACCUUAAGGAAAAUAA-5'(SEQ ID NO:2329)
KRAS-581靶:5'-GCAAGAAGTTATGGAATTCCTTTTATT-3'(SEQ ID NO:3735)
5'-AAGUUAUGGAAUUCCUUUUAUUGaa-3'(SEQ ID NO:3033)
3'-UCUUCAAUACCUUAAGGAAAAUAACUU-5'(SEQ ID NO:2330)
KRAS-584靶:5'-AGAAGTTATGGAATTCCTTTTATTGAA-3'(SEQ ID NO:3736)
5'-AGUUAUGGAAUUCCUUUUAUUGAaa-3'(SEQ ID NO:3034)
3'-CUUCAAUACCUUAAGGAAAAUAACUUU-5'(SEQ ID NO:2331)
KRAS-585靶:5'-GAAGTTATGGAATTCCTTTTATTGAAA-3'(SEQ ID NO:3737)
5'-GUUAUGGAAUUCCUUUUAUUGAAac-3'(SEQ ID NO:3035)
3'-UUCAAUACCUUAAGGAAAAUAACUUUG-5'(SEQ ID NO:2332)
KRAS-586靶:5'-AAGTTATGGAATTCCTTTTATTGAAAC-3'(SEQ ID NO:3738)
5'-UUAUGGAAUUCCUUUUAUUGAAAca-3'(SEQ ID NO:3036)
3'-UCAAUACCUUAAGGAAAAUAACUUUGU-5'(SEQ ID NO:2333)
KRAS-587靶:5'-AGTTATGGAATTCCTTTTATTGAAACA-3'(SEQ ID NO:3739)
5'-UGGAGGAUGCUUUUUAUACAUUGgt-3'(SEQ ID NO:3037)
3'-UCACCUCCUACGAAAAAUAUGUAACCA-5'(SEQ ID NO:2334)
KRAS-634靶:5'-AGTGGAGGATGCTTTTTATACATTGGT-3'(SEQ ID NO:3740)
5'-GAGGAUGCUUUUUAUACAUUGGUga-3'(SEQ ID NO:3038)
3'-ACCUCCUACGAAAAAUAUGUAACCACU-5'(SEQ ID NO:2335)
KRAS-636靶:5'-TGGAGGATGCTTTTTATACATTGGTGA-3'(SEQ ID NO:3741)
5'-ACAGAUUGAAAAAAAUCAGCAAAga-3'(SEQ ID NO:3039)
3'-UAUGUCUAACUUUUUUUAGUCGUUUCU-5'(SEQ ID NO:2336)
KRAS-676靶:5'-ATACAGATTGAAAAAAATCAGCAAAGA-3'(SEQ ID NO:3742)
5'-CAGAUUGAAAAAAAUCAGCAAAGaa-3'(SEQ ID NO:3040)
3'-AUGUCUAACUUUUUUUAGUCGUUUCUU-5'(SEQ ID NO:2337)
KRAS-677靶:5'-TACAGATTGAAAAAAATCAGCAAAGAA-3'(SEQ ID NO:3743)
5'-GAUUGAAAAAAAUCAGCAAAGAAga-3'(SEQ ID NO:3041)
3'-GUCUAACUUUUUUUAGUCGUUUCUUCU-5'(SEQ ID NO:2338)
KRAS-679靶:5'-CAGATTGAAAAAAATCAGCAAAGAAGA-3'(SEQ ID NO:3744)
5'-AUUGAAAAAAAUCAGCAAAGAAGaa-3'(SEQ ID NO:3042)
3'-UCUAACUUUUUUUAGUCGUUUCUUCUU-5'(SEQ ID NO:2339)
KRAS-680靶:5'-AGATTGAAAAAAATCAGCAAAGAAGAA-3'(SEQ ID NO:3745)
5'-UUGAAAAAAAUCAGCAAAGAAGAaa-3'(SEQ ID NO:3043)
3'-CUAACUUUUUUUAGUCGUUUCUUCUUU-5'(SEQ ID NO:2340)
KRAS-681靶:5'-GATTGAAAAAAATCAGCAAAGAAGAAA-3'(SEQ ID NO:3746)
5'-UGAAAAAAAUCAGCAAAGAAGAAaa-3'(SEQ ID NO:3044)
3'-UAACUUUUUUUAGUCGUUUCUUCUUUU-5'(SEQ ID NO:2341)
KRAS-682靶:5'-ATTGAAAAAAATCAGCAAAGAAGAAAA-3'(SEQ ID NO:3747)
5'-UCCUGGCUGUGUGAAAAUUAAAAaa-3'(SEQ ID NO:3045)
3'-UGAGGACCGACACACUUUUAAUUUUUU-5'(SEQ ID NO:2342)
KRAS-710靶:5'-ACTCCTGGCTGTGTGAAAATTAAAAAA-3'(SEQ ID NO:3748)
5'-GGCUGUGUGAAAAUUAAAAAAUGca-3'(SEQ ID NO:3046)
3'-GACCGACACACUUUUAAUUUUUUACGU-5'(SEQ ID NO:2343)
KRAS-714靶:5'-CTGGCTGTGTGAAAATTAAAAAATGCA-3'(SEQ ID NO:3749)
5'-GUGUGAAAAUUAAAAAAUGCAUUat-3'(SEQ ID NO:3047)
3'-GACACACUUUUAAUUUUUUACGUAAUA-5'(SEQ ID NO:2344)
KRAS-718靶:5'-CTGTGTGAAAATTAAAAAATGCATTAT-3'(SEQ ID NO:3750)
5'-UGUGAAAAUUAAAAAAUGCAUUAta-3'(SEQ ID NO:3048)
3'-ACACACUUUUAAUUUUUUACGUAAUAU-5'(SEQ ID NO:2345)
KRAS-719靶:5'-TGTGTGAAAATTAAAAAATGCATTATA-3'(SEQ ID NO:3751)
5'-GUGAAAAUUAAAAAAUGCAUUAUaa-3'(SEQ ID NO:3049)
3'-CACACUUUUAAUUUUUUACGUAAUAUU-5'(SEQ ID NO:2346)
KRAS-720靶:5'-GTGTGAAAATTAAAAAATGCATTATAA-3'(SEQ ID NO:3752)
5'-UGAAAAUUAAAAAAUGCAUUAUAat-3'(SEQ ID NO:3050)
3'-ACACUUUUAAUUUUUUACGUAAUAUUA-5'(SEQ ID NO:2347)
KRAS-721靶:5'-TGTGAAAATTAAAAAATGCATTATAAT-3'(SEQ ID NO:3753)
5'-AAAAUUAAAAAAUGCAUUAUAAUgt-3'(SEQ ID NO:3051)
3'-ACUUUUAAUUUUUUACGUAAUAUUACA-5'(SEQ ID NO:2348)
KRAS-723靶:5'-TGAAAATTAAAAAATGCATTATAATGT-3'(SEQ ID NO:3754)
5'-AAAUUAAAAAAUGCAUUAUAAUGta-3'(SEQ ID NO:3052)
3'-CUUUUAAUUUUUUACGUAAUAUUACAU-5'(SEQ ID NO:2349)
KRAS-724靶:5'-GAAAATTAAAAAATGCATTATAATGTA-3'(SEQ ID NO:3755)
5'-AAUUAAAAAAUGCAUUAUAAUGUaa-3'(SEQ ID NO:3053)
3'-UUUUAAUUUUUUACGUAAUAUUACAUU-5'(SEQ ID NO:2350)
KRAS-725靶:5'-AAAATTAAAAAATGCATTATAATGTAA-3'(SEQ ID NO:3756)
5'-AUUAAAAAAUGCAUUAUAAUGUAat-3'(SEQ ID NO:3054)
3'-UUUAAUUUUUUACGUAAUAUUACAUUA-5'(SEQ ID NO:2351)
KRAS-726靶:5'-AAATTAAAAAATGCATTATAATGTAAT-3'(SEQ ID NO:3757)
5'-UAAAAAAUGCAUUAUAAUGUAAUct-3'(SEQ ID NO:3055)
3'-UAAUUUUUUACGUAAUAUUACAUUAGA-5'(SEQ ID NO:2352)
KRAS-728靶:5'-ATTAAAAAATGCATTATAATGTAATCT-3'(SEQ ID NO:3758)
5'-UGCAUUAUAAUGUAAUCUGGGUGtt-3'(SEQ ID NO:3056)
3'-UUACGUAAUAUUACAUUAGACCCACAA-5'(SEQ ID NO:2353)
KRAS-735靶:5'-AATGCATTATAATGTAATCTGGGTGTT-3'(SEQ ID NO:3759)
5'-UUCGAGAAAUUCGAAAACAUAAAga-3'(SEQ ID NO:3057)
3'-UCAAGCUCUUUAAGCUUUUGUAUUUCU-5'(SEQ ID NO:2354)
KRAS-782靶:5'-AGTTCGAGAAATTCGAAAACATAAAGA-3'(SEQ ID NO:3760)
5'-UCGAGAAAUUCGAAAACAUAAAGaa-3'(SEQ ID NO:3058)
3'-CAAGCUCUUUAAGCUUUUGUAUUUCUU-5'(SEQ ID NO:2355)
KRAS-783靶:5'-GTTCGAGAAATTCGAAAACATAAAGAA-3'(SEQ ID NO:3761)
5'-CGAGAAAUUCGAAAACAUAAAGAaa-3'(SEQ ID NO:3059)
3'-AAGCUCUUUAAGCUUUUGUAUUUCUUU-5'(SEQ ID NO:2356)
KRAS-784靶:5'-TTCGAGAAATTCGAAAACATAAAGAAA-3'(SEQ ID NO:3762)
5'-GAAAUUCGAAAACAUAAAGAAAAga-3'(SEQ ID NO:3060)
3'-CUCUUUAAGCUUUUGUAUUUCUUUUCU-5'(SEQ ID NO:2357)
KRAS-787靶:5'-GAGAAATTCGAAAACATAAAGAAAAGA-3'(SEQ ID NO:3763)
5'-UCGAAAACAUAAAGAAAAGAUGAgc-3'(SEQ ID NO:3061)
3'-UAAGCUUUUGUAUUUCUUUUCUACUCG-5'(SEQ ID NO:2358)
KRAS-792靶:5'-ATTCGAAAACATAAAGAAAAGATGAGC-3'(SEQ ID NO:3764)
5'-CGAAAACAUAAAGAAAAGAUGAGca-3'(SEQ ID NO:3062)
3'-AAGCUUUUGUAUUUCUUUUCUACUCGU-5'(SEQ ID NO:2359)
KRAS-793靶:5'-TTCGAAAACATAAAGAAAAGATGAGCA-3'(SEQ ID NO:3765)
5'-AAAGAUGGUAAAAAGAAGAAAAAga-3'(SEQ ID NO:3063)
3'-CGUUUCUACCAUUUUUCUUCUUUUUCU-5'(SEQ ID NO:2360)
KRAS-817靶:5'-GCAAAGATGGTAAAAAGAAGAAAAAGA-3'(SEQ ID NO:3766)
5'-AAGAUGGUAAAAAGAAGAAAAAGaa-3'(SEQ ID NO:3064)
3'-GUUUCUACCAUUUUUCUUCUUUUUCUU-5'(SEQ ID NO:2361)
KRAS-818靶:5'-CAAAGATGGTAAAAAGAAGAAAAAGAA-3'(SEQ ID NO:3767)
5'-GAUGGUAAAAAGAAGAAAAAGAAgt-3'(SEQ ID NO:3065)
3'-UUCUACCAUUUUUCUUCUUUUUCUUCA-5'(SEQ ID NO:2362)
KRAS-820靶:5'-AAGATGGTAAAAAGAAGAAAAAGAAGT-3'(SEQ ID NO:3768)
5'-AUGGUAAAAAGAAGAAAAAGAAGtc-3'(SEQ ID NO:3066)
3'-UCUACCAUUUUUCUUCUUUUUCUUCAG-5'(SEQ ID NO:2363)
KRAS-821靶:5'-AGATGGTAAAAAGAAGAAAAAGAAGTC-3'(SEQ ID NO:3769)
5'-AAAAAGAAGAAAAAGAAGUCAAAga-3'(SEQ ID NO:3067)
3'-CAUUUUUCUUCUUUUUCUUCAGUUUCU-5'(SEQ ID NO:2364)
KRAS-826靶:5'-GTAAAAAGAAGAAAAAGAAGTCAAAGA-3'(SEQ ID NO:3770)
5'-AAAAGAAGAAAAAGAAGUCAAAGac-3'(SEQ ID NO:3068)
3'-AUUUUUCUUCUUUUUCUUCAGUUUCUG-5'(SEQ ID NO:2365)
KRAS-827靶:5'-TAAAAAGAAGAAAAAGAAGTCAAAGAC-3'(SEQ ID NO:3771)
5'-AAAGAAGAAAAAGAAGUCAAAGAca-3'(SEQ ID NO:3069)
3'-UUUUUCUUCUUUUUCUUCAGUUUCUGU-5'(SEQ ID NO:2366)
KRAS-828靶:5'-AAAAAGAAGAAAAAGAAGTCAAAGACA-3'(SEQ ID NO:3772)
5'-UCAAAGACAAAGUGUGUAAUUAUgt-3'(SEQ ID NO:3070)
3'-UCAGUUUCUGUUUCACACAUUAAUACA-5'(SEQ ID NO:2367)
KRAS-844靶:5'-AGTCAAAGACAAAGTGTGTAATTATGT-3'(SEQ ID NO:3773)
5'-CAAAGACAAAGUGUGUAAUUAUGta-3'(SEQ ID NO:3071)
3'-CAGUUUCUGUUUCACACAUUAAUACAU-5'(SEQ ID NO:2368)
KRAS-845靶:5'-GTCAAAGACAAAGTGTGTAATTATGTA-3'(SEQ ID NO:3774)
5'-GACAAAGUGUGUAAUUAUGUAAAta-3'(SEQ ID NO:3072)
3'-UUCUGUUUCACACAUUAAUACAUUUAU-5'(SEQ ID NO:2369)
KRAS-849靶:5'-AAGACAAAGTGTGTAATTATGTAAATA-3'(SEQ ID NO:3775)
5'-CAAAGUGUGUAAUUAUGUAAAUAca-3'(SEQ ID NO:3073)
3'-CUGUUUCACACAUUAAUACAUUUAUGU-5'(SEQ ID NO:2370)
KRAS-851靶:5'-GACAAAGTGTGTAATTATGTAAATACA-3'(SEQ ID NO:3776)
5'-GUGUGUAAUUAUGUAAAUACAAUtt-3'(SEQ ID NO:3074)
3'-UUCACACAUUAAUACAUUUAUGUUAAA-5'(SEQ ID NO:2371)
KRAS-855靶:5'-AAGTGTGTAATTATGTAAATACAATTT-3'(SEQ ID NO:3777)
5'-GUGUAAUUAUGUAAAUACAAUUUgt-3'(SEQ ID NO:3075)
3'-CACACAUUAAUACAUUUAUGUUAAACA-5'(SEQ ID NO:2372)
KRAS-857靶:5'-GTGTGTAATTATGTAAATACAATTTGT-3'(SEQ ID NO:3778)
5'-GUAAUUAUGUAAAUACAAUUUGUac-3'(SEQ ID NO:3076)
3'-CACAUUAAUACAUUUAUGUUAAACAUG-5'(SEQ ID NO:2373)
KRAS-859靶:5'-GTGTAATTATGTAAATACAATTTGTAC-3'(SEQ ID NO:3779)
5'-UAAUUAUGUAAAUACAAUUUGUAct-3'(SEQ ID NO:3077)
3'-ACAUUAAUACAUUUAUGUUAAACAUGA-5'(SEQ ID NO:2374)
KRAS-860靶:5'-TGTAATTATGTAAATACAATTTGTACT-3'(SEQ ID NO:3780)
5'-UAUGUAAAUACAAUUUGUACUUUtt-3'(SEQ ID NO:3078)
3'-UAAUACAUUUAUGUUAAACAUGAAAAA-5'(SEQ ID NO:2375)
KRAS-864靶:5'-ATTATGTAAATACAATTTGTACTTTTT-3'(SEQ ID NO:3781)
5'-AUGUAAAUACAAUUUGUACUUUUtt-3'(SEQ ID NO:3079)
3'-AAUACAUUUAUGUUAAACAUGAAAAAA-5'(SEQ ID NO:2376)
KRAS-865靶:5'-TTATGTAAATACAATTTGTACTTTTTT-3'(SEQ ID NO:3782)
5'-UGUAAAUACAAUUUGUACUUUUUtc-3'(SEQ ID NO:3080)
3'-AUACAUUUAUGUUAAACAUGAAAAAAG-5'(SEQ ID NO:2377)
KRAS-866靶:5'-TATGTAAATACAATTTGTACTTTTTTC-3'(SEQ ID NO:3783)
5'-GUAAAUACAAUUUGUACUUUUUUct-3'(SEQ ID NO:3081)
3'-UACAUUUAUGUUAAACAUGAAAAAAGA-5'(SEQ ID NO:2378)
KRAS-867靶:5'-ATGTAAATACAATTTGTACTTTTTTCT-3'(SEQ ID NO:3784)
5'-ACAAUUUGUACUUUUUUCUUAAGgc-3'(SEQ ID NO:3082)
3'-UAUGUUAAACAUGAAAAAAGAAUUCCG-5'(SEQ ID NO:2379)
KRAS-873靶:5'-ATACAATTTGTACTTTTTTCTTAAGGC-3'(SEQ ID NO:3785)
5'-CAAUUUGUACUUUUUUCUUAAGGca-3'(SEQ ID NO:3083)
3'-AUGUUAAACAUGAAAAAAGAAUUCCGU-5'(SEQ ID NO:2380)
KRAS-874靶:5'-TACAATTTGTACTTTTTTCTTAAGGCA-3'(SEQ ID NO:3786)
5'-UACUAGUACAAGUGGUAAUUUUUgt-3'(SEQ ID NO:3084)
3'-GUAUGAUCAUGUUCACCAUUAAAAACA-5'(SEQ ID NO:2381)
KRAS-899靶:5'-CATACTAGTACAAGTGGTAATTTTTGT-3'(SEQ ID NO:3787)
5'-ACUAGUACAAGUGGUAAUUUUUGta-3'(SEQ ID NO:3085)
3'-UAUGAUCAUGUUCACCAUUAAAAACAU-5'(SEQ ID NO:2382)
KRAS-900靶:5'-ATACTAGTACAAGTGGTAATTTTTGTA-3'(SEQ ID NO:3788)
5'-ACAAGUGGUAAUUUUUGUACAUUac-3'(SEQ ID NO:3086)
3'-CAUGUUCACCAUUAAAAACAUGUAAUG-5'(SEQ ID NO:2383)
KRAS-906靶:5'-GTACAAGTGGTAATTTTTGTACATTAC-3'(SEQ ID NO:3789)
5'-CAAGUGGUAAUUUUUGUACAUUAca-3'(SEQ ID NO:3087)
3'-AUGUUCACCAUUAAAAACAUGUAAUGU-5'(SEQ ID NO:2384)
KRAS-907靶:5'-TACAAGTGGTAATTTTTGTACATTACA-3'(SEQ ID NO:3790)
5'-UAAUUUUUGUACAUUACACUAAAtt-3'(SEQ ID NO:3088)
3'-CCAUUAAAAACAUGUAAUGUGAUUUAA-5'(SEQ ID NO:2385)
KRAS-914靶:5'-GGTAATTTTTGTACATTACACTAAATT-3'(SEQ ID NO:3791)
5'-AAUUUUUGUACAUUACACUAAAUta-3'(SEQ ID NO:3089)
3'-CAUUAAAAACAUGUAAUGUGAUUUAAU-5'(SEQ ID NO:2386)
KRAS-915靶:5'-GTAATTTTTGTACATTACACTAAATTA-3'(SEQ ID NO:3792)
5'-AUUUUUGUACAUUACACUAAAUUat-3'(SEQ ID NO:3090)
3'-AUUAAAAACAUGUAAUGUGAUUUAAUA-5'(SEQ ID NO:2387)
KRAS-916靶:5'-TAATTTTTGTACATTACACTAAATTAT-3'(SEQ ID NO:3793)
5'-UUUUUGUACAUUACACUAAAUUAtt-3'(SEQ ID NO:3091)
3'-UUAAAAACAUGUAAUGUGAUUUAAUAA-5'(SEQ ID NO:2388)
KRAS-917靶:5'-AATTTTTGTACATTACACTAAATTATT-3'(SEQ ID NO:3794)
5'-UUUUGUACAUUACACUAAAUUAUta-3'(SEQ ID NO:3092)
3'-UAAAAACAUGUAAUGUGAUUUAAUAAU-5'(SEQ ID NO:2389)
KRAS-918靶:5'-ATTTTTGTACATTACACTAAATTATTA-3'(SEQ ID NO:3795)
5'-CACUAAAUUAUUAGCAUUUGUUUta-3'(SEQ ID NO:3093)
3'-AUGUGAUUUAAUAAUCGUAAACAAAAU-5'(SEQ ID NO:2390)
KRAS-930靶:5'-TACACTAAATTATTAGCATTTGTTTTA-3'(SEQ ID NO:3796)
5'-CUAAAUUAUUAGCAUUUGUUUUAgc-3'(SEQ ID NO:3094)
3'-GUGAUUUAAUAAUCGUAAACAAAAUCG-5'(SEQ ID NO:2391)
KRAS-932靶:5'-CACTAAATTATTAGCATTTGTTTTAGC-3'(SEQ ID NO:3797)
5'-UAAAUUAUUAGCAUUUGUUUUAGca-3'(SEQ ID NO:3095)
3'-UGAUUUAAUAAUCGUAAACAAAAUCGU-5'(SEQ ID NO:2392)
KRAS-933靶:5'-ACTAAATTATTAGCATTTGTTTTAGCA-3'(SEQ ID NO:3798)
5'-UAUUAGCAUUUGUUUUAGCAUUAcc-3'(SEQ ID NO:3096)
3'-UAAUAAUCGUAAACAAAAUCGUAAUGG-5'(SEQ ID NO:2393)
KRAS-938靶:5'-ATTATTAGCATTTGTTTTAGCATTACC-3'(SEQ ID NO:3799)
5'-CAUUUGUUUUAGCAUUACCUAAUtt-3'(SEQ ID NO:3097)
3'-UCGUAAACAAAAUCGUAAUGGAUUAAA-5'(SEQ ID NO:2394)
KRAS-944靶:5'-AGCATTTGTTTTAGCATTACCTAATTT-3'(SEQ ID NO:3800)
5'-AUUUGUUUUAGCAUUACCUAAUUtt-3'(SEQ ID NO:3098)
3'-CGUAAACAAAAUCGUAAUGGAUUAAAA-5'(SEQ ID NO:2395)
KRAS-945靶:5'-GCATTTGTTTTAGCATTACCTAATTTT-3'(SEQ ID NO:3801)
5'-UUGUUUUAGCAUUACCUAAUUUUtt-3'(SEQ ID NO:3099)
3'-UAAACAAAAUCGUAAUGGAUUAAAAAA-5'(SEQ ID NO:2396)
KRAS-947靶:5'-ATTTGTTTTAGCATTACCTAATTTTTT-3'(SEQ ID NO:3802)
5'-UGUUUUAGCAUUACCUAAUUUUUtt-3'(SEQ ID NO:3100)
3'-AAACAAAAUCGUAAUGGAUUAAAAAAA-5'(SEQ ID NO:2397)
KRAS-948靶:5'-TTTGTTTTAGCATTACCTAATTTTTTT-3'(SEQ ID NO:3803)
5'-GUUUUAGCAUUACCUAAUUUUUUtc-3'(SEQ ID NO:3101)
3'-AACAAAAUCGUAAUGGAUUAAAAAAAG-5'(SEQ ID NO:2398)
KRAS-949靶:5'-TTGTTTTAGCATTACCTAATTTTTTTC-3'(SEQ ID NO:3804)
5'-UUUUAGCAUUACCUAAUUUUUUUcc-3'(SEQ ID NO:3102)
3'-ACAAAAUCGUAAUGGAUUAAAAAAAGG-5'(SEQ ID NO:2399)
KRAS-950靶:5'-TGTTTTAGCATTACCTAATTTTTTTCC-3'(SEQ ID NO:3805)
5'-GACUGUUAGCUUUUACCUUAAAUgc-3'(SEQ ID NO:3103)
3'-GUCUGACAAUCGAAAAUGGAAUUUACG-5'(SEQ ID NO:2400)
KRAS-986靶:5'-CAGACTGTTAGCTTTTACCTTAAATGC-3'(SEQ ID NO:3806)
5'-ACUGUUAGCUUUUACCUUAAAUGct-3'(SEQ ID NO:3104)
3'-UCUGACAAUCGAAAAUGGAAUUUACGA-5'(SEQ ID NO:2401)
KRAS-987靶:5'-AGACTGTTAGCTTTTACCTTAAATGCT-3'(SEQ ID NO:3807)
5'-AGCUUUUACCUUAAAUGCUUAUUtt-3'(SEQ ID NO:3105)
3'-AAUCGAAAAUGGAAUUUACGAAUAAAA-5'(SEQ ID NO:2402)
KRAS-993靶:5'-TTAGCTTTTACCTTAAATGCTTATTTT-3'(SEQ ID NO:3808)
5'-GCUUUUACCUUAAAUGCUUAUUUta-3'(SEQ ID NO:3106)
3'-AUCGAAAAUGGAAUUUACGAAUAAAAU-5'(SEQ ID NO:2403)
KRAS-994靶:5'-TAGCTTTTACCTTAAATGCTTATTTTA-3'(SEQ ID NO:3809)
5'-CUUUUACCUUAAAUGCUUAUUUUaa-3'(SEQ ID NO:3107)
3'-UCGAAAAUGGAAUUUACGAAUAAAAUU-5'(SEQ ID NO:2404)
KRAS-995靶:5'-AGCTTTTACCTTAAATGCTTATTTTAA-3'(SEQ ID NO:3810)
5'-CCUUAAAUGCUUAUUUUAAAAUGac-3'(SEQ ID NO:3108)
3'-AUGGAAUUUACGAAUAAAAUUUUACUG-5'(SEQ ID NO:2405)
KRAS-1001靶:5'-TACCTTAAATGCTTATTTTAAAATGAC-3'(SEQ ID NO:3811)
5'-CUUAAAUGCUUAUUUUAAAAUGAca-3'(SEQ ID NO:3109)
3'-UGGAAUUUACGAAUAAAAUUUUACUGU-5'(SEQ ID NO:2406)
KRAS-1002靶:5'-ACCTTAAATGCTTATTTTAAAATGACA-3'(SEQ ID NO:3812)
5'-UGCUUAUUUUAAAAUGACAGUGGaa-3'(SEQ ID NO:3110)
3'-UUACGAAUAAAAUUUUACUGUCACCUU-5'(SEQ ID NO:2407)
KRAS-1008靶:5'-AATGCTTATTTTAAAATGACAGTGGAA-3'(SEQ ID NO:3813)
5'-CUUAUUUUAAAAUGACAGUGGAAgt-3'(SEQ ID NO:3111)
3'-ACGAAUAAAAUUUUACUGUCACCUUCA-5'(SEQ ID NO:2408)
KRAS-1010靶:5'-TGCTTATTTTAAAATGACAGTGGAAGT-3'(SEQ ID NO:3814)
5'-GUGGAAGUUUUUUUUUCCUCUAAgt-3'(SEQ ID NO:3112)
3'-GUCACCUUCAAAAAAAAAGGAGAUUCA-5'(SEQ ID NO:2409)
KRAS-1027靶:5'-CAGTGGAAGTTTTTTTTTCCTCTAAGT-3'(SEQ ID NO:3815)
5'-GGAAGUUUUUUUUUCCUCUAAGUgc-3'(SEQ ID NO:3113)
3'-CACCUUCAAAAAAAAAGGAGAUUCACG-5'(SEQ ID NO:2410)
KRAS-1029靶:5'-GTGGAAGTTTTTTTTTCCTCTAAGTGC-3'(SEQ ID NO:3816)
5'-GAAGUUUUUUUUUCCUCUAAGUGcc-3'(SEQ ID NO:3114)
3'-ACCUUCAAAAAAAAAGGAGAUUCACGG-5'(SEQ ID NO:2411)
KRAS-1030靶:5'-TGGAAGTTTTTTTTTCCTCTAAGTGCC-3'(SEQ ID NO:3817)
5'-UUUUGGUUUUUGAACUAGCAAUGcc-3'(SEQ ID NO:3115)
3'-UCAAAACCAAAAACUUGAUCGUUACGG-5'(SEQ ID NO:2412)
KRAS-1068靶:5'-AGTTTTGGTTTTTGAACTAGCAATGCC-3'(SEQ ID NO:3818)
5'-GCCUGUGAAAAAGAAACUGAAUAcc-3'(SEQ ID NO:3116)
3'-UACGGACACUUUUUCUUUGACUUAUGG-5'(SEQ ID NO:2413)
KRAS-1090靶:5'-ATGCCTGTGAAAAAGAAACTGAATACC-3'(SEQ ID NO:3819)
5'-AAAAAGAAACUGAAUACCUAAGAtt-3'(SEQ ID NO:3117)
3'-ACUUUUUCUUUGACUUAUGGAUUCUAA-5'(SEQ ID NO:2414)
KRAS-1097靶:5'-TGAAAAAGAAACTGAATACCTAAGATT-3'(SEQ ID NO:3820)
5'-AAAAGAAACUGAAUACCUAAGAUtt-3'(SEQ ID NO:3118)
3'-CUUUUUCUUUGACUUAUGGAUUCUAAA-5'(SEQ ID NO:2415)
KRAS-1098靶:5'-GAAAAAGAAACTGAATACCTAAGATTT-3'(SEQ ID NO:3821)
5'-AACUGAAUACCUAAGAUUUCUGUct-3'(SEQ ID NO:3119)
3'-CUUUGACUUAUGGAUUCUAAAGACAGA-5'(SEQ ID NO:2416)
KRAS-1104靶:5'-GAAACTGAATACCTAAGATTTCTGTCT-3'(SEQ ID NO:3822)
5'-UGCAGUUGAUUACUUCUUAUUUUtc-3'(SEQ ID NO:3120)
3'-GUACGUCAACUAAUGAAGAAUAAAAAG-5'(SEQ ID NO:2417)
KRAS-1145靶:5'-CATGCAGTTGATTACTTCTTATTTTTC-3'(SEQ ID NO:3823)
5'-GCAGUUGAUUACUUCUUAUUUUUct-3'(SEQ ID NO:3121)
3'-UACGUCAACUAAUGAAGAAUAAAAAGA-5'(SEQ ID NO:2418)
KRAS-1146靶:5'-ATGCAGTTGATTACTTCTTATTTTTCT-3'(SEQ ID NO:3824)
5'-UUGAUUACUUCUUAUUUUUCUUAcc-3'(SEQ ID NO:3122)
3'-UCAACUAAUGAAGAAUAAAAAGAAUGG-5'(SEQ ID NO:2419)
KRAS-1150靶:5'-AGTTGATTACTTCTTATTTTTCTTACC-3'(SEQ ID NO:3825)
5'-UUCUUAUUUUUCUUACCAAUUGUga-3'(SEQ ID NO:3123)
3'-UGAAGAAUAAAAAGAAUGGUUAACACU-5'(SEQ ID NO:2420)
KRAS-1158靶:5'-ACTTCTTATTTTTCTTACCAATTGTGA-3'(SEQ ID NO:3826)
5'-UCUUAUUUUUCUUACCAAUUGUGaa-3'(SEQ ID NO:3124)
3'-GAAGAAUAAAAAGAAUGGUUAACACUU-5'(SEQ ID NO:2421)
KRAS-1159靶:5'-CTTCTTATTTTTCTTACCAATTGTGAA-3'(SEQ ID NO:3827)
5'-CUUAUUUUUCUUACCAAUUGUGAat-3'(SEQ ID NO:3125)
3'-AAGAAUAAAAAGAAUGGUUAACACUUA-5'(SEQ ID NO:2422)
KRAS-1160靶:5'-TTCTTATTTTTCTTACCAATTGTGAAT-3'(SEQ ID NO:3828)
5'-AUGUUGGUGUGAAACAAAUUAAUga-3'(SEQ ID NO:3126)
3'-CUUACAACCACACUUUGUUUAAUUACU-5'(SEQ ID NO:2423)
KRAS-1183靶:5'-GAATGTTGGTGTGAAACAAATTAATGA-3'(SEQ ID NO:3829)
5'-UUGGUGUGAAACAAAUUAAUGAAgc-3'(SEQ ID NO:3127)
3'-ACAACCACACUUUGUUUAAUUACUUCG-5'(SEQ ID NO:2424)
KRAS-1186靶:5'-TGTTGGTGTGAAACAAATTAATGAAGC-3'(SEQ ID NO:3830)
5'-UGGUGUGAAACAAAUUAAUGAAGct-3'(SEQ ID NO:3128)
3'-CAACCACACUUUGUUUAAUUACUUCGA-5'(SEQ ID NO:2425)
KRAS-1187靶:5'-GTTGGTGTGAAACAAATTAATGAAGCT-3'(SEQ ID NO:3831)
5'-AACAAAUUAAUGAAGCUUUUGAAtc-3'(SEQ ID NO:3129)
3'-CUUUGUUUAAUUACUUCGAAAACUUAG-5'(SEQ ID NO:2426)
KRAS-1195靶:5'-GAAACAAATTAATGAAGCTTTTGAATC-3'(SEQ ID NO:3832)
5'-ACAAAUUAAUGAAGCUUUUGAAUca-3'(SEQ ID NO:3130)
3'-UUUGUUUAAUUACUUCGAAAACUUAGU-5'(SEQ ID NO:2427)
KRAS-1196靶:5'-AAACAAATTAATGAAGCTTTTGAATCA-3'(SEQ ID NO:3833)
5'-UCUGUGUUUUAUCUAGUCACAUAaa-3'(SEQ ID NO:3131)
3'-UAAGACACAAAAUAGAUCAGUGUAUUU-5'(SEQ ID NO:2428)
KRAS-1228靶:5'-ATTCTGTGTTTTATCTAGTCACATAAA-3'(SEQ ID NO:3834)
5'-CUGUGUUUUAUCUAGUCACAUAAat-3'(SEQ ID NO:3132)
3'-AAGACACAAAAUAGAUCAGUGUAUUUA-5'(SEQ ID NO:2429)
KRAS-1229靶:5'-TTCTGTGTTTTATCTAGTCACATAAAT-3'(SEQ ID NO:3835)
5'-UGUUUUAUCUAGUCACAUAAAUGga-3'(SEQ ID NO:3133)
3'-ACACAAAAUAGAUCAGUGUAUUUACCU-5'(SEQ ID NO:2430)
KRAS-1232靶:5'-TGTGTTTTATCTAGTCACATAAATGGA-3'(SEQ ID NO:3836)
5'-GUUUUAUCUAGUCACAUAAAUGGat-3'(SEQ ID NO:3134)
3'-CACAAAAUAGAUCAGUGUAUUUACCUA-5'(SEQ ID NO:2431)
KRAS-1233靶:5'-GTGTTTTATCTAGTCACATAAATGGAT-3'(SEQ ID NO:3837)
5'-AUCUAGUCACAUAAAUGGAUUAAtt-3'(SEQ ID NO:3135)
3'-AAUAGAUCAGUGUAUUUACCUAAUUAA-5'(SEQ ID NO:2432)
KRAS-1238靶:5'-TTATCTAGTCACATAAATGGATTAATT-3'(SEQ ID NO:3838)
5'-UCUAGUCACAUAAAUGGAUUAAUta-3'(SEQ ID NO:3136)
3'-AUAGAUCAGUGUAUUUACCUAAUUAAU-5'(SEQ ID NO:2433)
KRAS-1239靶:5'-TATCTAGTCACATAAATGGATTAATTA-3'(SEQ ID NO:3839)
5'-CAUAAAUGGAUUAAUUACUAAUUtc-3'(SEQ ID NO:3137)
3'-GUGUAUUUACCUAAUUAAUGAUUAAAG-5'(SEQ ID NO:2434)
KRAS-1247靶:5'-CACATAAATGGATTAATTACTAATTTC-3'(SEQ ID NO:3840)
5'-AUAAAUGGAUUAAUUACUAAUUUca-3'(SEQ ID NO:3138)
3'-UGUAUUUACCUAAUUAAUGAUUAAAGU-5'(SEQ ID NO:2435)
KRAS-1248靶:5'-ACATAAATGGATTAATTACTAATTTCA-3'(SEQ ID NO:3841)
5'-UGGAUUAAUUACUAAUUUCAGUUga-3'(SEQ ID NO:3139)
3'-UUACCUAAUUAAUGAUUAAAGUCAACU-5'(SEQ ID NO:2436)
KRAS-1253靶:5'-AATGGATTAATTACTAATTTCAGTTGA-3'(SEQ ID NO:3842)
5'-GAUUAAUUACUAAUUUCAGUUGAga-3'(SEQ ID NO:3140)
3'-ACCUAAUUAAUGAUUAAAGUCAACUCU-5'(SEQ ID NO:2437)
KRAS-1255靶:5'-TGGATTAATTACTAATTTCAGTTGAGA-3'(SEQ ID NO:3843)
5'-AUUAAUUACUAAUUUCAGUUGAGac-3'(SEQ ID NO:3141)
3'-CCUAAUUAAUGAUUAAAGUCAACUCUG-5'(SEQ ID NO:2438)
KRAS-1256靶:5'-GGATTAATTACTAATTTCAGTTGAGAC-3'(SEQ ID NO:3844)
5'-UUAAUUACUAAUUUCAGUUGAGAcc-3'(SEQ ID NO:3142)
3'-CUAAUUAAUGAUUAAAGUCAACUCUGG-5'(SEQ ID NO:2439)
KRAS-1257靶:5'-GATTAATTACTAATTTCAGTTGAGACC-3'(SEQ ID NO:3845)
5'-UAAUUGGUUUUUACUGAAACAUUga-3'(SEQ ID NO:3143)
3'-AGAUUAACCAAAAAUGACUUUGUAACU-5'(SEQ ID NO:2440)
KRAS-1285靶:5'-TCTAATTGGTTTTTACTGAAACATTGA-3'(SEQ ID NO:3846)
5'-UGGUUUUUACUGAAACAUUGAGGga-3'(SEQ ID NO:3144)
3'-UAACCAAAAAUGACUUUGUAACUCCCU-5'(SEQ ID NO:2441)
KRAS-1289靶:5'-ATTGGTTTTTACTGAAACATTGAGGGA-3'(SEQ ID NO:3847)
5'-GGUUUUUACUGAAACAUUGAGGGaa-3'(SEQ ID NO:3145)
3'-AACCAAAAAUGACUUUGUAACUCCCUU-5'(SEQ ID NO:2442)
KRAS-1290靶:5'-TTGGTTTTTACTGAAACATTGAGGGAA-3'(SEQ ID NO:3848)
5'-AUUGAGGGAACACAAAUUUAUGGgc-3'(SEQ ID NO:3146)
3'-UGUAACUCCCUUGUGUUUAAAUACCCG-5'(SEQ ID NO:2443)
KRAS-1305靶:5'-ACATTGAGGGAACACAAATTTATGGGC-3'(SEQ ID NO:3849)
5'-UUGAGGGAACACAAAUUUAUGGGct-3'(SEQ ID NO:3147)
3'-GUAACUCCCUUGUGUUUAAAUACCCGA-5'(SEQ ID NO:2444)
KRAS-1306靶:5'-CATTGAGGGAACACAAATTTATGGGCT-3'(SEQ ID NO:3850)
5'-UGAUGAAUGUAAAGUUACACUGUtc-3'(SEQ ID NO:3148)
3'-GGACUACUUACAUUUCAAUGUGACAAG-5'(SEQ ID NO:2445)
KRAS-1379靶:5'-CCTGATGAATGTAAAGTTACACTGTTC-3'(SEQ ID NO:3851)
5'-GAUGAAUGUAAAGUUACACUGUUca-3'(SEQ ID NO:3149)
3'-GACUACUUACAUUUCAAUGUGACAAGU-5'(SEQ ID NO:2446)
KRAS-1380靶:5'-CTGATGAATGTAAAGTTACACTGTTCA-3'(SEQ ID NO:3852)
5'-CCAAAAUAUUAUAUUUUUUCUAUaa-3'(SEQ ID NO:3150)
3'-GGGGUUUUAUAAUAUAAAAAAGAUAUU-5'(SEQ ID NO:2447)
KRAS-1452靶:5'-CCCCAAAATATTATATTTTTTCTATAA-3'(SEQ ID NO:3853)
5'-CAAAAUAUUAUAUUUUUUCUAUAaa-3'(SEQ ID NO:3151)
3'-GGGUUUUAUAAUAUAAAAAAGAUAUUU-5'(SEQ ID NO:2448)
KRAS-1453靶:5'-CCCAAAATATTATATTTTTTCTATAAA-3'(SEQ ID NO:3854)
5'-AAAAUAUUAUAUUUUUUCUAUAAaa-3'(SEQ ID NO:3152)
3'-GGUUUUAUAAUAUAAAAAAGAUAUUUU-5'(SEQ ID NO:2449)
KRAS-1454靶:5'-CCAAAATATTATATTTTTTCTATAAAA-3'(SEQ ID NO:3855)
5'-AAAUAUUAUAUUUUUUCUAUAAAaa-3'(SEQ ID NO:3153)
3'-GUUUUAUAAUAUAAAAAAGAUAUUUUU-5'(SEQ ID NO:2450)
KRAS-1455靶:5'-CAAAATATTATATTTTTTCTATAAAAA-3'(SEQ ID NO:3856)
5'-AUAUUAUAUUUUUUCUAUAAAAAga-3'(SEQ ID NO:3154)
3'-UUUAUAAUAUAAAAAAGAUAUUUUUCU-5'(SEQ ID NO:2451)
KRAS-1457靶:5'-AAATATTATATTTTTTCTATAAAAAGA-3'(SEQ ID NO:3857)
5'-UAUUAUAUUUUUUCUAUAAAAAGaa-3'(SEQ ID NO:3155)
3'-UUAUAAUAUAAAAAAGAUAUUUUUCUU-5'(SEQ ID NO:2452)
KRAS-1458靶:5'-AATATTATATTTTTTCTATAAAAAGAA-3'(SEQ ID NO:3858)
5'-AUUAUAUUUUUUCUAUAAAAAGAaa-3'(SEQ ID NO:3156)
3'-UAUAAUAUAAAAAAGAUAUUUUUCUUU-5'(SEQ ID NO:2453)
KRAS-1459靶:5'-ATATTATATTTTTTCTATAAAAAGAAA-3'(SEQ ID NO:3859)
5'-UUAUAUUUUUUCUAUAAAAAGAAaa-3'(SEQ ID NO:3157)
3'-AUAAUAUAAAAAAGAUAUUUUUCUUUU-5'(SEQ ID NO:2454)
KRAS-1460靶:5'-TATTATATTTTTTCTATAAAAAGAAAA-3'(SEQ ID NO:3860)
5'-UAUAUUUUUUCUAUAAAAAGAAAaa-3'(SEQ ID NO:3158)
3'-UAAUAUAAAAAAGAUAUUUUUCUUUUU-5'(SEQ ID NO:2455)
KRAS-1461靶:5'-ATTATATTTTTTCTATAAAAAGAAAAA-3'(SEQ ID NO:3861)
5'-AUAUUUUUUCUAUAAAAAGAAAAaa-3'(SEQ ID NO:3159)
3'-AAUAUAAAAAAGAUAUUUUUCUUUUUU-5'(SEQ ID NO:2456)
KRAS-1462靶:5'-TTATATTTTTTCTATAAAAAGAAAAAA-3'(SEQ ID NO:3862)
5'-UAUUUUUUCUAUAAAAAGAAAAAaa-3'(SEQ ID NO:3160)
3'-AUAUAAAAAAGAUAUUUUUCUUUUUUU-5'(SEQ ID NO:2457)
KRAS-1463靶:5'-TATATTTTTTCTATAAAAAGAAAAAAA-3'(SEQ ID NO:3863)
5'-AUUUUUUCUAUAAAAAGAAAAAAat-3'(SEQ ID NO:3161)
3'-UAUAAAAAAGAUAUUUUUCUUUUUUUA-5'(SEQ ID NO:2458)
KRAS-1464靶:5'-ATATTTTTTCTATAAAAAGAAAAAAAT-3'(SEQ ID NO:3864)
5'-UUCUAUAAAAAGAAAAAAAUGGAaa-3'(SEQ ID NO:3162)
3'-AAAAGAUAUUUUUCUUUUUUUACCUUU-5'(SEQ ID NO:2459)
KRAS-1469靶:5'-TTTTCTATAAAAAGAAAAAAATGGAAA-3'(SEQ ID NO:3865)
5'-UCUAUAAAAAGAAAAAAAUGGAAaa-3'(SEQ ID NO:3163)
3'-AAAGAUAUUUUUCUUUUUUUACCUUUU-5'(SEQ ID NO:2460)
KRAS-1470靶:5'-TTTCTATAAAAAGAAAAAAATGGAAAA-3'(SEQ ID NO:3866)
5'-UAUAAAAAGAAAAAAAUGGAAAAaa-3'(SEQ ID NO:3164)
3'-AGAUAUUUUUCUUUUUUUACCUUUUUU-5'(SEQ ID NO:2461)
KRAS-1472靶:5'-TCTATAAAAAGAAAAAAATGGAAAAAA-3'(SEQ ID NO:3867)
5'-AUAAAAAGAAAAAAAUGGAAAAAaa-3'(SEQ ID NO:3165)
3'-GAUAUUUUUCUUUUUUUACCUUUUUUU-5'(SEQ ID NO:2462)
KRAS-1473靶:5'-CTATAAAAAGAAAAAAATGGAAAAAAA-3'(SEQ ID NO:3868)
5'-UAAAAAGAAAAAAAUGGAAAAAAat-3'(SEQ ID NO:3166)
3'-AUAUUUUUCUUUUUUUACCUUUUUUUA-5'(SEQ ID NO:2463)
KRAS-1474靶:5'-TATAAAAAGAAAAAAATGGAAAAAAAT-3'(SEQ ID NO:3869)
5'-AAAAAGAAAAAAAUGGAAAAAAAtt-3'(SEQ ID NO:3167)
3'-UAUUUUUCUUUUUUUACCUUUUUUUAA-5'(SEQ ID NO:2464)
KRAS-1475靶:5'-ATAAAAAGAAAAAAATGGAAAAAAATT-3'(SEQ ID NO:3870)
5'-AAAAGAAAAAAAUGGAAAAAAAUta-3'(SEQ ID NO:3168)
3'-AUUUUUCUUUUUUUACCUUUUUUUAAU-5'(SEQ ID NO:2465)
KRAS-1476靶:5'-TAAAAAGAAAAAAATGGAAAAAAATTA-3'(SEQ ID NO:3871)
5'-AAAGAAAAAAAUGGAAAAAAAUUac-3'(SEQ ID NO:3169)
3'-UUUUUCUUUUUUUACCUUUUUUUAAUG-5'(SEQ ID NO:2466)
KRAS-1477靶:5'-AAAAAGAAAAAAATGGAAAAAAATTAC-3'(SEQ ID NO:3872)
5'-AAGAAAAAAAUGGAAAAAAAUUAca-3'(SEQ ID NO:3170)
3'-UUUUCUUUUUUUACCUUUUUUUAAUGU-5'(SEQ ID NO:2467)
KRAS-1478靶:5'-AAAAGAAAAAAATGGAAAAAAATTACA-3'(SEQ ID NO:3873)
5'-AAAAAAUGGAAAAAAAUUACAAGgc-3'(SEQ ID NO:3171)
3'-CUUUUUUUACCUUUUUUUAAUGUUCCG-5'(SEQ ID NO:2468)
KRAS-1482靶:5'-GAAAAAAATGGAAAAAAATTACAAGGC-3'(SEQ ID NO:3874)
5'-AAAAAUGGAAAAAAAUUACAAGGca-3'(SEQ ID NO:3172)
3'-UUUUUUUACCUUUUUUUAAUGUUCCGU-5'(SEQ ID NO:2469)
KRAS-1483靶:5'-AAAAAAATGGAAAAAAATTACAAGGCA-3'(SEQ ID NO:3875)
5'-UGGAAAAAAAUUACAAGGCAAUGga-3'(SEQ ID NO:3173)
3'-UUACCUUUUUUUAAUGUUCCGUUACCU-5'(SEQ ID NO:2470)
KRAS-1488靶:5'-AATGGAAAAAAATTACAAGGCAATGGA-3'(SEQ ID NO:3876)
5'-GGAAAAAAAUUACAAGGCAAUGGaa-3'(SEQ ID NO:3174)
3'-UACCUUUUUUUAAUGUUCCGUUACCUU-5'(SEQ ID NO:2471)
KRAS-1489靶:5'-ATGGAAAAAAATTACAAGGCAATGGAA-3'(SEQ ID NO:3877)
5'-GAAAAAAAUUACAAGGCAAUGGAaa-3'(SEQ ID NO:3175)
3'-ACCUUUUUUUAAUGUUCCGUUACCUUU-5'(SEQ ID NO:2472)
KRAS-1490靶:5'-TGGAAAAAAATTACAAGGCAATGGAAA-3'(SEQ ID NO:3878)
5'-GCCAUUUCCUUUUCACAUUAGAUaa-3'(SEQ ID NO:3176)
3'-UCCGGUAAAGGAAAAGUGUAAUCUAUU-5'(SEQ ID NO:2473)
KRAS-1525靶:5'-AGGCCATTTCCTTTTCACATTAGATAA-3'(SEQ ID NO:3879)
5'-UCCUUUUCACAUUAGAUAAAUUAct-3'(SEQ ID NO:3177)
3'-AAAGGAAAAGUGUAAUCUAUUUAAUGA-5'(SEQ ID NO:2474)
KRAS-1531靶:5'-TTTCCTTTTCACATTAGATAAATTACT-3'(SEQ ID NO:3880)
5'-CACAUUAGAUAAAUUACUAUAAAga-3'(SEQ ID NO:3178)
3'-AAGUGUAAUCUAUUUAAUGAUAUUUCU-5'(SEQ ID NO:2475)
KRAS-1538靶:5'-TTCACATTAGATAAATTACTATAAAGA-3'(SEQ ID NO:3881)
5'-ACAUUAGAUAAAUUACUAUAAAGac-3'(SEQ ID NO:3179)
3'-AGUGUAAUCUAUUUAAUGAUAUUUCUG-5'(SEQ ID NO:2476)
KRAS-1539靶:5'-TCACATTAGATAAATTACTATAAAGAC-3'(SEQ ID NO:3882)
5'-CAUUAGAUAAAUUACUAUAAAGAct-3'(SEQ ID NO:3180)
3'-GUGUAAUCUAUUUAAUGAUAUUUCUGA-5'(SEQ ID NO:2477)
KRAS-1540靶:5'-CACATTAGATAAATTACTATAAAGACT-3'(SEQ ID NO:3883)
5'-AGUAUGAAAUGGGGAUUAUUAUAgc-3'(SEQ ID NO:3181)
3'-GGUCAUACUUUACCCCUAAUAAUAUCG-5'(SEQ ID NO:2478)
KRAS-1595靶:5'-CCAGTATGAAATGGGGATTATTATAGC-3'(SEQ ID NO:3884)
5'-UGGGGAUUAUUAUAGCAACCAUUtt-3'(SEQ ID NO:3182)
3'-UUACCCCUAAUAAUAUCGUUGGUAAAA-5'(SEQ ID NO:2479)
KRAS-1604靶:5'-AATGGGGATTATTATAGCAACCATTTT-3'(SEQ ID NO:3885)
5'-GGCUAUAUUUACAUGCUACUAAAtt-3'(SEQ ID NO:3183)
3'-CCCCGAUAUAAAUGUACGAUGAUUUAA-5'(SEQ ID NO:2480)
KRAS-1631靶:5'-GGGGCTATATTTACATGCTACTAAATT-3'(SEQ ID NO:3886)
5'-GCUAUAUUUACAUGCUACUAAAUtt-3'(SEQ ID NO:3184)
3'-CCCGAUAUAAAUGUACGAUGAUUUAAA-5'(SEQ ID NO:2481)
KRAS-1632靶:5'-GGGCTATATTTACATGCTACTAAATTT-3'(SEQ ID NO:3887)
5'-CUAUAUUUACAUGCUACUAAAUUtt-3'(SEQ ID NO:3185)
3'-CCGAUAUAAAUGUACGAUGAUUUAAAA-5'(SEQ ID NO:2482)
KRAS-1633靶:5'-GGCTATATTTACATGCTACTAAATTTT-3'(SEQ ID NO:3888)
5'-UAUAUUUACAUGCUACUAAAUUUtt-3'(SEQ ID NO:3186)
3'-CGAUAUAAAUGUACGAUGAUUUAAAAA-5'(SEQ ID NO:2483)
KRAS-1634靶:5'-GCTATATTTACATGCTACTAAATTTTT-3'(SEQ ID NO:3889)
5'-AUAUUUACAUGCUACUAAAUUUUta-3'(SEQ ID NO:3187)
3'-GAUAUAAAUGUACGAUGAUUUAAAAAU-5'(SEQ ID NO:2484)
KRAS-1635靶:5'-CTATATTTACATGCTACTAAATTTTTA-3'(SEQ ID NO:3890)
5'-UACAUGCUACUAAAUUUUUAUAAta-3'(SEQ ID NO:3188)
3'-AAAUGUACGAUGAUUUAAAAAUAUUAU-5'(SEQ ID NO:2485)
KRAS-1640靶:5'-TTTACATGCTACTAAATTTTTATAATA-3'(SEQ ID NO:3891)
5'-UACUAAAUUUUUAUAAUAAUUGAaa-3'(SEQ ID NO:3189)
3'-CGAUGAUUUAAAAAUAUUAUUAACUUU-5'(SEQ ID NO:2486)
KRAS-1647靶:5'-GCTACTAAATTTTTATAATAATTGAAA-3'(SEQ ID NO:3892)
5'-ACUAAAUUUUUAUAAUAAUUGAAaa-3'(SEQ ID NO:3190)
3'-GAUGAUUUAAAAAUAUUAUUAACUUUU-5'(SEQ ID NO:2487)
KRAS-1648靶:5'-CTACTAAATTTTTATAATAATTGAAAA-3'(SEQ ID NO:3893)
5'-UAAAUUUUUAUAAUAAUUGAAAAga-3'(SEQ ID NO:3191)
3'-UGAUUUAAAAAUAUUAUUAACUUUUCU-5'(SEQ ID NO:2488)
KRAS-1650靶:5'-ACTAAATTTTTATAATAATTGAAAAGA-3'(SEQ ID NO:3894)
5'-AAAUUUUUAUAAUAAUUGAAAAGat-3'(SEQ ID NO:3192)
3'-GAUUUAAAAAUAUUAUUAACUUUUCUA-5'(SEQ ID NO:2489)
KRAS-1651靶:5'-CTAAATTTTTATAATAATTGAAAAGAT-3'(SEQ ID NO:3895)
5'-AAUUUUUAUAAUAAUUGAAAAGAtt-3'(SEQ ID NO:3193)
3'-AUUUAAAAAUAUUAUUAACUUUUCUAA-5'(SEQ ID NO:2490)
KRAS-1652靶:5'-TAAATTTTTATAATAATTGAAAAGATT-3'(SEQ ID NO:3896)
5'-AUUUUUAUAAUAAUUGAAAAGAUtt-3'(SEQ ID NO:3194)
3'-UUUAAAAAUAUUAUUAACUUUUCUAAA-5'(SEQ ID NO:2491)
KRAS-1653靶:5'-AAATTTTTATAATAATTGAAAAGATTT-3'(SEQ ID NO:3897)
5'-UUUUUAUAAUAAUUGAAAAGAUUtt-3'(SEQ ID NO:3195)
3'-UUAAAAAUAUUAUUAACUUUUCUAAAA-5'(SEQ ID NO:2492)
KRAS-1654靶:5'-AATTTTTATAATAATTGAAAAGATTTT-3'(SEQ ID NO:3898)
5'-UUUUAUAAUAAUUGAAAAGAUUUta-3'(SEQ ID NO:3196)
3'-UAAAAAUAUUAUUAACUUUUCUAAAAU-5'(SEQ ID NO:2493)
KRAS-1655靶:5'-ATTTTTATAATAATTGAAAAGATTTTA-3'(SEQ ID NO:3899)
5'-UUUAUAAUAAUUGAAAAGAUUUUaa-3'(SEQ ID NO:3197)
3'-AAAAAUAUUAUUAACUUUUCUAAAAUU-5'(SEQ ID NO:2494)
KRAS-1656靶:5'-TTTTTATAATAATTGAAAAGATTTTAA-3'(SEQ ID NO:3900)
5'-UUAUAAUAAUUGAAAAGAUUUUAac-3'(SEQ ID NO:3198)
3'-AAAAUAUUAUUAACUUUUCUAAAAUUG-5'(SEQ ID NO:2495)
KRAS-1657靶:5'-TTTTATAATAATTGAAAAGATTTTAAC-3'(SEQ ID NO:3901)
5'-UAUAAUAAUUGAAAAGAUUUUAAca-3'(SEQ ID NO:3199)
3'-AAAUAUUAUUAACUUUUCUAAAAUUGU-5'(SEQ ID NO:2496)
KRAS-1658靶:5'-TTTATAATAATTGAAAAGATTTTAACA-3'(SEQ ID NO:3902)
5'-AUAAUUGAAAAGAUUUUAACAAGta-3'(SEQ ID NO:3200)
3'-AUUAUUAACUUUUCUAAAAUUGUUCAU-5'(SEQ ID NO:2497)
KRAS-1662靶:5'-TAATAATTGAAAAGATTTTAACAAGTA-3'(SEQ ID NO:3903)
5'-UAAUUGAAAAGAUUUUAACAAGUat-3'(SEQ ID NO:3201)
3'-UUAUUAACUUUUCUAAAAUUGUUCAUA-5'(SEQ ID NO:2498)
KRAS-1663靶:5'-AATAATTGAAAAGATTTTAACAAGTAT-3'(SEQ ID NO:3904)
5'-AUUGAAAAGAUUUUAACAAGUAUaa-3'(SEQ ID NO:3202)
3'-AUUAACUUUUCUAAAAUUGUUCAUAUU-5'(SEQ ID NO:2499)
KRAS-1665靶:5'-TAATTGAAAAGATTTTAACAAGTATAA-3'(SEQ ID NO:3905)
5'-UUGAAAAGAUUUUAACAAGUAUAaa-3'(SEQ ID NO:3203)
3'-UUAACUUUUCUAAAAUUGUUCAUAUUU-5'(SEQ ID NO:2500)
KRAS-1666靶:5'-AATTGAAAAGATTTTAACAAGTATAAA-3'(SEQ ID NO:3906)
5'-UGAAAAGAUUUUAACAAGUAUAAaa-3'(SEQ ID NO:3204)
3'-UAACUUUUCUAAAAUUGUUCAUAUUUU-5'(SEQ ID NO:2501)
KRAS-1667靶:5'-ATTGAAAAGATTTTAACAAGTATAAAA-3'(SEQ ID NO:3907)
5'-GAAAAGAUUUUAACAAGUAUAAAaa-3'(SEQ ID NO:3205)
3'-AACUUUUCUAAAAUUGUUCAUAUUUUU-5'(SEQ ID NO:2502)
KRAS-1668靶:5'-TTGAAAAGATTTTAACAAGTATAAAAA-3'(SEQ ID NO:3908)
5'-AAAAGAUUUUAACAAGUAUAAAAaa-3'(SEQ ID NO:3206)
3'-ACUUUUCUAAAAUUGUUCAUAUUUUUU-5'(SEQ ID NO:2503)
KRAS-1669靶:5'-TGAAAAGATTTTAACAAGTATAAAAAA-3'(SEQ ID NO:3909)
5'-AAAGAUUUUAACAAGUAUAAAAAat-3'(SEQ ID NO:3207)
3'-CUUUUCUAAAAUUGUUCAUAUUUUUUA-5'(SEQ ID NO:2504)
KRAS-1670靶:5'-GAAAAGATTTTAACAAGTATAAAAAAT-3'(SEQ ID NO:3910)
5'-AAGAUUUUAACAAGUAUAAAAAAtt-3'(SEQ ID NO:3208)
3'-UUUUCUAAAAUUGUUCAUAUUUUUUAA-5'(SEQ ID NO:2505)
KRAS-1671靶:5'-AAAAGATTTTAACAAGTATAAAAAATT-3'(SEQ ID NO:3911)
5'-AGAUUUUAACAAGUAUAAAAAAUtc-3'(SEQ ID NO:3209)
3'-UUUCUAAAAUUGUUCAUAUUUUUUAAG-5'(SEQ ID NO:2506)
KRAS-1672靶:5'-AAAGATTTTAACAAGTATAAAAAATTC-3'(SEQ ID NO:3912)
5'-GAUUUUAACAAGUAUAAAAAAUUct-3'(SEQ ID NO:3210)
3'-UUCUAAAAUUGUUCAUAUUUUUUAAGA-5'(SEQ ID NO:2507)
KRAS-1673靶:5'-AAGATTTTAACAAGTATAAAAAATTCT-3'(SEQ ID NO:3913)
5'-ACAAGUAUAAAAAAUUCUCAUAGga-3'(SEQ ID NO:3211)
3'-AUUGUUCAUAUUUUUUAAGAGUAUCCU-5'(SEQ ID NO:2508)
KRAS-1680靶:5'-TAACAAGTATAAAAAATTCTCATAGGA-3'(SEQ ID NO:3914)
5'-CAAGUAUAAAAAAUUCUCAUAGGaa-3'(SEQ ID NO:3212)
3'-UUGUUCAUAUUUUUUAAGAGUAUCCUU-5'(SEQ ID NO:2509)
KRAS-1681靶:5'-AACAAGTATAAAAAATTCTCATAGGAA-3'(SEQ ID NO:3915)
5'-AAGUAUAAAAAAUUCUCAUAGGAat-3'(SEQ ID NO:3213)
3'-UGUUCAUAUUUUUUAAGAGUAUCCUUA-5'(SEQ ID NO:2510)
KRAS-1682靶:5'-ACAAGTATAAAAAATTCTCATAGGAAT-3'(SEQ ID NO:3916)
5'-AGUAUAAAAAAUUCUCAUAGGAAtt-3'(SEQ ID NO:3214)
3'-GUUCAUAUUUUUUAAGAGUAUCCUUAA-5'(SEQ ID NO:2511)
KRAS-1683靶:5'-CAAGTATAAAAAATTCTCATAGGAATT-3'(SEQ ID NO:3917)
5'-GUAUAAAAAAUUCUCAUAGGAAUta-3'(SEQ ID NO:3215)
3'-UUCAUAUUUUUUAAGAGUAUCCUUAAU-5'(SEQ ID NO:2512)
KRAS-1684靶:5'-AAGTATAAAAAATTCTCATAGGAATTA-3'(SEQ ID NO:3918)
5'-UAUAAAAAAUUCUCAUAGGAAUUaa-3'(SEQ ID NO:3216)
3'-UCAUAUUUUUUAAGAGUAUCCUUAAUU-5'(SEQ ID NO:2513)
KRAS-1685靶:5'-AGTATAAAAAATTCTCATAGGAATTAA-3'(SEQ ID NO:3919)
5'-AUAAAAAAUUCUCAUAGGAAUUAaa-3'(SEQ ID NO:3217)
3'-CAUAUUUUUUAAGAGUAUCCUUAAUUU-5'(SEQ ID NO:2514)
KRAS-1686靶:5'-GTATAAAAAATTCTCATAGGAATTAAA-3'(SEQ ID NO:3920)
5'-UAAAAAAUUCUCAUAGGAAUUAAat-3'(SEQ ID NO:3218)
3'-AUAUUUUUUAAGAGUAUCCUUAAUUUA-5'(SEQ ID NO:2515)
KRAS-1687靶:5'-TATAAAAAATTCTCATAGGAATTAAAT-3'(SEQ ID NO:3921)
5'-AAAAAUUCUCAUAGGAAUUAAAUgt-3'(SEQ ID NO:3219)
3'-AUUUUUUAAGAGUAUCCUUAAUUUACA-5'(SEQ ID NO:2516)
KRAS-1689靶:5'-TAAAAAATTCTCATAGGAATTAAATGT-3'(SEQ ID NO:3922)
5'-AAAAUUCUCAUAGGAAUUAAAUGta-3'(SEQ ID NO:3220)
3'-UUUUUUAAGAGUAUCCUUAAUUUACAU-5'(SEQ ID NO:2517)
KRAS-1690靶:5'-AAAAAATTCTCATAGGAATTAAATGTA-3'(SEQ ID NO:3923)
5'-CUCUUUCAUAGUAUAACUUUAAAtc-3'(SEQ ID NO:3221)
3'-ACGAGAAAGUAUCAUAUUGAAAUUUAG-5'(SEQ ID NO:2518)
KRAS-1734靶:5'-TGCTCTTTCATAGTATAACTTTAAATC-3'(SEQ ID NO:3924)
5'-UCAUAGUAUAACUUUAAAUCUUUtc-3'(SEQ ID NO:3222)
3'-AAAGUAUCAUAUUGAAAUUUAGAAAAG-5'(SEQ ID NO:2519)
KRAS-1739靶:5'-TTTCATAGTATAACTTTAAATCTTTTC-3'(SEQ ID NO:3925)
5'-CAUAGUAUAACUUUAAAUCUUUUct-3'(SEQ ID NO:3223)
3'-AAGUAUCAUAUUGAAAUUUAGAAAAGA-5'(SEQ ID NO:2520)
KRAS-1740靶:5'-TTCATAGTATAACTTTAAATCTTTTCT-3'(SEQ ID NO:3926)
5'-UUUAAAUCUUUUCUUCAACUUGAgt-3'(SEQ ID NO:3224)
3'-UGAAAUUUAGAAAAGAAGUUGAACUCA-5'(SEQ ID NO:2521)
KRAS-1751靶:5'-ACTTTAAATCTTTTCTTCAACTTGAGT-3'(SEQ ID NO:3927)
5'-UUAAAUCUUUUCUUCAACUUGAGtc-3'(SEQ ID NO:3225)
3'-GAAAUUUAGAAAAGAAGUUGAACUCAG-5'(SEQ ID NO:2522)
KRAS-1752靶:5'-CTTTAAATCTTTTCTTCAACTTGAGTC-3'(SEQ ID NO:3928)
5'-AACUUGAGUCUUUGAAGAUAGUUtt-3'(SEQ ID NO:3226)
3'-AGUUGAACUCAGAAACUUCUAUCAAAA-5'(SEQ ID NO:2523)
KRAS-1767靶:5'-TCAACTTGAGTCTTTGAAGATAGTTTT-3'(SEQ ID NO:3929)
5'-CUUGAGUCUUUGAAGAUAGUUUUaa-3'(SEQ ID NO:3227)
3'-UUGAACUCAGAAACUUCUAUCAAAAUU-5'(SEQ ID NO:2524)
KRAS-1769靶:5'-AACTTGAGTCTTTGAAGATAGTTTTAA-3'(SEQ ID NO:3930)
5'-UUGAGUCUUUGAAGAUAGUUUUAat-3'(SEQ ID NO:3228)
3'-UGAACUCAGAAACUUCUAUCAAAAUUA-5'(SEQ ID NO:2525)
KRAS-1770靶:5'-ACTTGAGTCTTTGAAGATAGTTTTAAT-3'(SEQ ID NO:3931)
5'-AAGAUAGUUUUAAUUCUGCUUGUga-3'(SEQ ID NO:3229)
3'-ACUUCUAUCAAAAUUAAGACGAACACU-5'(SEQ ID NO:2526)
KRAS-1781靶:5'-TGAAGATAGTTTTAATTCTGCTTGTGA-3'(SEQ ID NO:3932)
5'-AGAUAGUUUUAAUUCUGCUUGUGac-3'(SEQ ID NO:3230)
3'-CUUCUAUCAAAAUUAAGACGAACACUG-5'(SEQ ID NO:2527)
KRAS-1782靶:5'-GAAGATAGTTTTAATTCTGCTTGTGAC-3'(SEQ ID NO:3933)
5'-GAUAGUUUUAAUUCUGCUUGUGAca-3'(SEQ ID NO:3231)
3'-UUCUAUCAAAAUUAAGACGAACACUGU-5'(SEQ ID NO:2528)
KRAS-1783靶:5'-AAGATAGTTTTAATTCTGCTTGTGACA-3'(SEQ ID NO:3934)
5'-UGCUUGUGACAUUAAAAGAUUAUtt-3'(SEQ ID NO:3232)
3'-AGACGAACACUGUAAUUUUCUAAUAAA-5'(SEQ ID NO:2529)
KRAS-1797靶:5'-TCTGCTTGTGACATTAAAAGATTATTT-3'(SEQ ID NO:3935)
5'-AGCAUUGCUUUUGUUUCUUAAGAaa-3'(SEQ ID NO:3233)
3'-UCUCGUAACGAAAACAAAGAAUUCUUU-5'(SEQ ID NO:2530)
KRAS-2045靶:5'-AGAGCATTGCTTTTGTTTCTTAAGAAA-3'(SEQ ID NO:3936)
5'-GCAUUGCUUUUGUUUCUUAAGAAaa-3'(SEQ ID NO:3234)
3'-CUCGUAACGAAAACAAAGAAUUCUUUU-5'(SEQ ID NO:2531)
KRAS-2046靶:5'-GAGCATTGCTTTTGTTTCTTAAGAAAA-3'(SEQ ID NO:3937)
5'-CUUUUGUUUCUUAAGAAAACAAAct-3'(SEQ ID NO:3235)
3'-ACGAAAACAAAGAAUUCUUUUGUUUGA-5'(SEQ ID NO:2532)
KRAS-2052靶:5'-TGCTTTTGTTTCTTAAGAAAACAAACT-3'(SEQ ID NO:3938)
5'-UUCUUAAGAAAACAAACUCUUUUtt-3'(SEQ ID NO:3236)
3'-CAAAGAAUUCUUUUGUUUGAGAAAAAA-5'(SEQ ID NO:2533)
KRAS-2059靶:5'-GTTTCTTAAGAAAACAAACTCTTTTTT-3'(SEQ ID NO:3939)
5'-UCUUAAGAAAACAAACUCUUUUUta-3'(SEQ ID NO:3237)
3'-AAAGAAUUCUUUUGUUUGAGAAAAAAU-5'(SEQ ID NO:2534)
KRAS-2060靶:5'-TTTCTTAAGAAAACAAACTCTTTTTTA-3'(SEQ ID NO:3940)
5'-CUUAAGAAAACAAACUCUUUUUUaa-3'(SEQ ID NO:3238)
3'-AAGAAUUCUUUUGUUUGAGAAAAAAUU-5'(SEQ ID NO:2535)
KRAS-2061靶:5'-TTCTTAAGAAAACAAACTCTTTTTTAA-3'(SEQ ID NO:3941)
5'-UUAAGAAAACAAACUCUUUUUUAaa-3'(SEQ ID NO:3239)
3'-AGAAUUCUUUUGUUUGAGAAAAAAUUU-5'(SEQ ID NO:2536)
KRAS-2062靶:5'-TCTTAAGAAAACAAACTCTTTTTTAAA-3'(SEQ ID NO:3942)
5'-UAAGAAAACAAACUCUUUUUUAAaa-3'(SEQ ID NO:3240)
3'-GAAUUCUUUUGUUUGAGAAAAAAUUUU-5'(SEQ ID NO:2537)
KRAS-2063靶:5'-CTTAAGAAAACAAACTCTTTTTTAAAA-3'(SEQ ID NO:3943)
5'-AAGAAAACAAACUCUUUUUUAAAaa-3'(SEQ ID NO:3241)
3'-AAUUCUUUUGUUUGAGAAAAAAUUUUU-5'(SEQ ID NO:2538)
KRAS-2064靶:5'-TTAAGAAAACAAACTCTTTTTTAAAAA-3'(SEQ ID NO:3944)
5'-AGAAAACAAACUCUUUUUUAAAAat-3'(SEQ ID NO:3242)
3'-AUUCUUUUGUUUGAGAAAAAAUUUUUA-5'(SEQ ID NO:2539)
KRAS-2065靶:5'-TAAGAAAACAAACTCTTTTTTAAAAAT-3'(SEQ ID NO:3945)
5'-AACAAACUCUUUUUUAAAAAUUAct-3'(SEQ ID NO:3243)
3'-UUUUGUUUGAGAAAAAAUUUUUAAUGA-5'(SEQ ID NO:2540)
KRAS-2069靶:5'-AAAACAAACTCTTTTTTAAAAATTACT-3'(SEQ ID NO:3946)
5'-CUCUUUUUUAAAAAUUACUUUUAaa-3'(SEQ ID NO:3244)
3'-UUGAGAAAAAAUUUUUAAUGAAAAUUU-5'(SEQ ID NO:2541)
KRAS-2075靶:5'-AACTCTTTTTTAAAAATTACTTTTAAA-3'(SEQ ID NO:3947)
5'-UCUUUUUUAAAAAUUACUUUUAAat-3'(SEQ ID NO:3245)
3'-UGAGAAAAAAUUUUUAAUGAAAAUUUA-5'(SEQ ID NO:2542)
KRAS-2076靶:5'-ACTCTTTTTTAAAAATTACTTTTAAAT-3'(SEQ ID NO:3948)
5'-CUUUUUUAAAAAUUACUUUUAAAta-3'(SEQ ID NO:3246)
3'-GAGAAAAAAUUUUUAAUGAAAAUUUAU-5'(SEQ ID NO:2543)
KRAS-2077靶:5'-CTCTTTTTTAAAAATTACTTTTAAATA-3'(SEQ ID NO:3949)
5'-UUUUUUAAAAAUUACUUUUAAAUat-3'(SEQ ID NO:3247)
3'-AGAAAAAAUUUUUAAUGAAAAUUUAUA-5'(SEQ ID NO:2544)
KRAS-2078靶:5'-TCTTTTTTAAAAATTACTTTTAAATAT-3'(SEQ ID NO:3950)
5'-UUUUUAAAAAUUACUUUUAAAUAtt-3'(SEQ ID NO:3248)
3'-GAAAAAAUUUUUAAUGAAAAUUUAUAA-5'(SEQ ID NO:2545)
KRAS-2079靶:5'-CTTTTTTAAAAATTACTTTTAAATATT-3'(SEQ ID NO:3951)
5'-UUUUAAAAAUUACUUUUAAAUAUta-3'(SEQ ID NO:3249)
3'-AAAAAAUUUUUAAUGAAAAUUUAUAAU-5'(SEQ ID NO:2546)
KRAS-2080靶:5'-TTTTTTAAAAATTACTTTTAAATATTA-3'(SEQ ID NO:3952)
5'-UUUAAAAAUUACUUUUAAAUAUUaa-3'(SEQ ID NO:3250)
3'-AAAAAUUUUUAAUGAAAAUUUAUAAUU-5'(SEQ ID NO:2547)
KRAS-2081靶:5'-TTTTTAAAAATTACTTTTAAATATTAA-3'(SEQ ID NO:3953)
5'-UUAAAAAUUACUUUUAAAUAUUAac-3'(SEQ ID NO:3251)
3'-AAAAUUUUUAAUGAAAAUUUAUAAUUG-5'(SEQ ID NO:2548)
KRAS-2082靶:5'-TTTTAAAAATTACTTTTAAATATTAAC-3'(SEQ ID NO:3954)
5'-UAAAAAUUACUUUUAAAUAUUAAct-3'(SEQ ID NO:3252)
3'-AAAUUUUUAAUGAAAAUUUAUAAUUGA-5'(SEQ ID NO:2549)
KRAS-2083靶:5'-TTTAAAAATTACTTTTAAATATTAACT-3'(SEQ ID NO:3955)
5'-UACUUUUAAAUAUUAACUCAAAAgt-3'(SEQ ID NO:3253)
3'-UAAUGAAAAUUUAUAAUUGAGUUUUCA-5'(SEQ ID NO:2550)
KRAS-2090靶:5'-ATTACTTTTAAATATTAACTCAAAAGT-3'(SEQ ID NO:3956)
5'-ACUUUUAAAUAUUAACUCAAAAGtt-3'(SEQ ID NO:3254)
3'-AAUGAAAAUUUAUAAUUGAGUUUUCAA-5'(SEQ ID NO:2551)
KRAS-2091靶:5'-TTACTTTTAAATATTAACTCAAAAGTT-3'(SEQ ID NO:3957)
5'-UUUUAAAUAUUAACUCAAAAGUUga-3'(SEQ ID NO:3255)
3'-UGAAAAUUUAUAAUUGAGUUUUCAACU-5'(SEQ ID NO:2552)
KRAS-2093靶:5'-ACTTTTAAATATTAACTCAAAAGTTGA-3'(SEQ ID NO:3958)
5'-UUAAAUAUUAACUCAAAAGUUGAga-3'(SEQ ID NO:3256)
3'-AAAAUUUAUAAUUGAGUUUUCAACUCU-5'(SEQ ID NO:2553)
KRAS-2095靶:5'-TTTTAAATATTAACTCAAAAGTTGAGA-3'(SEQ ID NO:3959)
5'-UAAAUAUUAACUCAAAAGUUGAGat-3'(SEQ ID NO:3257)
3'-AAAUUUAUAAUUGAGUUUUCAACUCUA-5'(SEQ ID NO:2554)
KRAS-2096靶:5'-TTTAAATATTAACTCAAAAGTTGAGAT-3'(SEQ ID NO:3960)
5'-AAAUAUUAACUCAAAAGUUGAGAtt-3'(SEQ ID NO:3258)
3'-AAUUUAUAAUUGAGUUUUCAACUCUAA-5'(SEQ ID NO:2555)
KRAS-2097靶:5'-TTAAATATTAACTCAAAAGTTGAGATT-3'(SEQ ID NO:3961)
5'-AAUAUUAACUCAAAAGUUGAGAUtt-3'(SEQ ID NO:3259)
3'-AUUUAUAAUUGAGUUUUCAACUCUAAA-5'(SEQ ID NO:2556)
KRAS-2098靶:5'-TAAATATTAACTCAAAAGTTGAGATTT-3'(SEQ ID NO:3962)
5'-GGUGUGCCAAGACAUUAAUUUUUtt-3'(SEQ ID NO:3260)
3'-CACCACACGGUUCUGUAAUUAAAAAAA-5'(SEQ ID NO:2557)
KRAS-2132靶:5'-GTGGTGTGCCAAGACATTAATTTTTTT-3'(SEQ ID NO:3963)
5'-GCCAAGACAUUAAUUUUUUUUUUaa-3'(SEQ ID NO:3261)
3'-CACGGUUCUGUAAUUAAAAAAAAAAUU-5'(SEQ ID NO:2558)
KRAS-2137靶:5'-GTGCCAAGACATTAATTTTTTTTTTAA-3'(SEQ ID NO:3964)
5'-CCAAGACAUUAAUUUUUUUUUUAaa-3'(SEQ ID NO:3262)
3'-ACGGUUCUGUAAUUAAAAAAAAAAUUU-5'(SEQ ID NO:2559)
KRAS-2138靶:5'-TGCCAAGACATTAATTTTTTTTTTAAA-3'(SEQ ID NO:3965)
5'-CAUUAAUUUUUUUUUUAAACAAUga-3'(SEQ ID NO:3263)
3'-CUGUAAUUAAAAAAAAAAUUUGUUACU-5'(SEQ ID NO:2560)
KRAS-2144靶:5'-GACATTAATTTTTTTTTTAAACAATGA-3'(SEQ ID NO:3966)
5'-AUUAAUUUUUUUUUUAAACAAUGaa-3'(SEQ ID NO:3264)
3'-UGUAAUUAAAAAAAAAAUUUGUUACUU-5'(SEQ ID NO:2561)
KRAS-2145靶:5'-ACATTAATTTTTTTTTTAAACAATGAA-3'(SEQ ID NO:3967)
5'-UAAUUUUUUUUUUAAACAAUGAAgt-3'(SEQ ID NO:3265)
3'-UAAUUAAAAAAAAAAUUUGUUACUUCA-5'(SEQ ID NO:2562)
KRAS-2147靶:5'-ATTAATTTTTTTTTTAAACAATGAAGT-3'(SEQ ID NO:3968)
5'-AUUUUUUUUUUAAACAAUGAAGUga-3'(SEQ ID NO:3266)
3'-AUUAAAAAAAAAAUUUGUUACUUCACU-5'(SEQ ID NO:2563)
KRAS-2149靶:5'-TAATTTTTTTTTTAAACAATGAAGTGA-3'(SEQ ID NO:3969)
5'-UUUUUUUUUUAAACAAUGAAGUGaa-3'(SEQ ID NO:3267)
3'-UUAAAAAAAAAAUUUGUUACUUCACUU-5'(SEQ ID NO:2564)
KRAS-2150靶:5'-AATTTTTTTTTTAAACAATGAAGTGAA-3'(SEQ ID NO:3970)
5'-UUUUUUUUUAAACAAUGAAGUGAaa-3'(SEQ ID NO:3268)
3'-UAAAAAAAAAAUUUGUUACUUCACUUU-5'(SEQ ID NO:2565)
KRAS-2151靶:5'-ATTTTTTTTTTAAACAATGAAGTGAAA-3'(SEQ ID NO:3971)
5'-UUUUUUUUAAACAAUGAAGUGAAaa-3'(SEQ ID NO:3269)
3'-AAAAAAAAAAUUUGUUACUUCACUUUU-5'(SEQ ID NO:2566)
KRAS-2152靶:5'-TTTTTTTTTTAAACAATGAAGTGAAAA-3'(SEQ ID NO:3972)
5'-UUUUUUUAAACAAUGAAGUGAAAaa-3'(SEQ ID NO:3270)
3'-AAAAAAAAAUUUGUUACUUCACUUUUU-5'(SEQ ID NO:2567)
KRAS-2153靶:5'-TTTTTTTTTAAACAATGAAGTGAAAAA-3'(SEQ ID NO:3973)
5'-UUUUUAAACAAUGAAGUGAAAAAgt-3'(SEQ ID NO:3271)
3'-AAAAAAAUUUGUUACUUCACUUUUUCA-5'(SEQ ID NO:2568)
KRAS-2155靶:5'-TTTTTTTAAACAATGAAGTGAAAAAGT-3'(SEQ ID NO:3974)
5'-UUUUAAACAAUGAAGUGAAAAAGtt-3'(SEQ ID NO:3272)
3'-AAAAAAUUUGUUACUUCACUUUUUCAA-5'(SEQ ID NO:2569)
KRAS-2156靶:5'-TTTTTTAAACAATGAAGTGAAAAAGTT-3'(SEQ ID NO:3975)
5'-UUUAAACAAUGAAGUGAAAAAGUtt-3'(SEQ ID NO:3273)
3'-AAAAAUUUGUUACUUCACUUUUUCAAA-5'(SEQ ID NO:2570)
KRAS-2157靶:5'-TTTTTAAACAATGAAGTGAAAAAGTTT-3'(SEQ ID NO:3976)
5'-AUGAAGUGAAAAAGUUUUACAAUct-3'(SEQ ID NO:3274)
3'-GUUACUUCACUUUUUCAAAAUGUUAGA-5'(SEQ ID NO:2571)
KRAS-2165靶:5'-CAATGAAGTGAAAAAGTTTTACAATCT-3'(SEQ ID NO:3977)
5'-UGAAAAAGUUUUACAAUCUCUAGgt-3'(SEQ ID NO:3275)
3'-UCACUUUUUCAAAAUGUUAGAGAUCCA-5'(SEQ ID NO:2572)
KRAS-2171靶:5'-AGTGAAAAAGTTTTACAATCTCTAGGT-3'(SEQ ID NO:3978)
5'-GAAAAAGUUUUACAAUCUCUAGGtt-3'(SEQ ID NO:3276)
3'-CACUUUUUCAAAAUGUUAGAGAUCCAA-5'(SEQ ID NO:2573)
KRAS-2172靶:5'-GTGAAAAAGTTTTACAATCTCTAGGTT-3'(SEQ ID NO:3979)
5'-AAAAAGUUUUACAAUCUCUAGGUtt-3'(SEQ ID NO:3277)
3'-ACUUUUUCAAAAUGUUAGAGAUCCAAA-5'(SEQ ID NO:2574)
KRAS-2173靶:5'-TGAAAAAGTTTTACAATCTCTAGGTTT-3'(SEQ ID NO:3980)
5'-ACUGGUUAAAUUAACAUUGCAUAaa-3'(SEQ ID NO:3278)
3'-UGUGACCAAUUUAAUUGUAACGUAUUU-5'(SEQ ID NO:2575)
KRAS-2214靶:5'-ACACTGGTTAAATTAACATTGCATAAA-3'(SEQ ID NO:3981)
5'-CUGGUUAAAUUAACAUUGCAUAAac-3'(SEQ ID NO:3279)
3'-GUGACCAAUUUAAUUGUAACGUAUUUG-5'(SEQ ID NO:2576)
KRAS-2215靶:5'-CACTGGTTAAATTAACATTGCATAAAC-3'(SEQ ID NO:3982)
5'-UGGUUAAAUUAACAUUGCAUAAAca-3'(SEQ ID NO:3280)
3'-UGACCAAUUUAAUUGUAACGUAUUUGU-5'(SEQ ID NO:2577)
KRAS-2216靶:5'-ACTGGTTAAATTAACATTGCATAAACA-3'(SEQ ID NO:3983)
5'-ACAUUGCAUAAACACUUUUCAAGtc-3'(SEQ ID NO:3281)
3'-AUUGUAACGUAUUUGUGAAAAGUUCAG-5'(SEQ ID NO:2578)
KRAS-2227靶:5'-TAACATTGCATAAACACTTTTCAAGTC-3'(SEQ ID NO:3984)
5'-UCAAGUCUGAUCCAUAUUUAAUAat-3'(SEQ ID NO:3282)
3'-AAAGUUCAGACUAGGUAUAAAUUAUUA-5'(SEQ ID NO:2579)
KRAS-2245靶:5'-TTTCAAGTCTGATCCATATTTAATAAT-3'(SEQ ID NO:3985)
5'-UCCAUAUUUAAUAAUGCUUUAAAat-3'(SEQ ID NO:3283)
3'-CUAGGUAUAAAUUAUUACGAAAUUUUA-5'(SEQ ID NO:2580)
KRAS-2255靶:5'-GATCCATATTTAATAATGCTTTAAAAT-3'(SEQ ID NO:3986)
5'-CCAUAUUUAAUAAUGCUUUAAAAta-3'(SEQ ID NO:3284)
3'-UAGGUAUAAAUUAUUACGAAAUUUUAU-5'(SEQ ID NO:2581)
KRAS-2256靶:5'-ATCCATATTTAATAATGCTTTAAAATA-3'(SEQ ID NO:3987)
5'-CAUAUUUAAUAAUGCUUUAAAAUaa-3'(SEQ ID NO:3285)
3'-AGGUAUAAAUUAUUACGAAAUUUUAUU-5'(SEQ ID NO:2582)
KRAS-2257靶:5'-TCCATATTTAATAATGCTTTAAAATAA-3'(SEQ ID NO:3988)
5'-AUAUUUAAUAAUGCUUUAAAAUAaa-3'(SEQ ID NO:3286)
3'-GGUAUAAAUUAUUACGAAAUUUUAUUU-5'(SEQ ID NO:2583)
KRAS-2258靶:5'-CCATATTTAATAATGCTTTAAAATAAA-3'(SEQ ID NO:3989)
5'-UAUUUAAUAAUGCUUUAAAAUAAaa-3'(SEQ ID NO:3287)
3'-GUAUAAAUUAUUACGAAAUUUUAUUUU-5'(SEQ ID NO:2584)
KRAS-2259靶:5'-CATATTTAATAATGCTTTAAAATAAAA-3'(SEQ ID NO:3990)
5'-AUUUAAUAAUGCUUUAAAAUAAAaa-3'(SEQ ID NO:3288)
3'-UAUAAAUUAUUACGAAAUUUUAUUUUU-5'(SEQ ID NO:2585)
KRAS-2260靶:5'-ATATTTAATAATGCTTTAAAATAAAAA-3'(SEQ ID NO:3991)
5'-UUAAUAAUGCUUUAAAAUAAAAAta-3'(SEQ ID NO:3289)
3'-UAAAUUAUUACGAAAUUUUAUUUUUAU-5'(SEQ ID NO:2586)
KRAS-2262靶:5'-ATTTAATAATGCTTTAAAATAAAAATA-3'(SEQ ID NO:3992)
5'-UAAUAAUGCUUUAAAAUAAAAAUaa-3'(SEQ ID NO:3290)
3'-AAAUUAUUACGAAAUUUUAUUUUUAUU-5'(SEQ ID NO:2587)
KRAS-2263靶:5'-TTTAATAATGCTTTAAAATAAAAATAA-3'(SEQ ID NO:3993)
5'-AAUAAUGCUUUAAAAUAAAAAUAaa-3'(SEQ ID NO:3291)
3'-AAUUAUUACGAAAUUUUAUUUUUAUUU-5'(SEQ ID NO:2588)
KRAS-2264靶:5'-TTAATAATGCTTTAAAATAAAAATAAA-3'(SEQ ID NO:3994)
5'-AUAAUGCUUUAAAAUAAAAAUAAaa-3'(SEQ ID NO:3292)
3'-AUUAUUACGAAAUUUUAUUUUUAUUUU-5'(SEQ ID NO:2589)
KRAS-2265靶:5'-TAATAATGCTTTAAAATAAAAATAAAA-3'(SEQ ID NO:3995)
5'-UUUAAAAUAAAAAUAAAAACAAUcc-3'(SEQ ID NO:3293)
3'-CGAAAUUUUAUUUUUAUUUUUGUUAGG-5'(SEQ ID NO:2590)
KRAS-2272靶:5'-GCTTTAAAATAAAAATAAAAACAATCC-3'(SEQ ID NO:3996)
5'-AUAAAAAUAAAAACAAUCCUUUUga-3'(SEQ ID NO:3294)
3'-UUUAUUUUUAUUUUUGUUAGGAAAACU-5'(SEQ ID NO:2591)
KRAS-2278靶:5'-AAATAAAAATAAAAACAATCCTTTTGA-3'(SEQ ID NO:3997)
5'-UAAAAAUAAAAACAAUCCUUUUGat-3'(SEQ ID NO:3295)
3'-UUAUUUUUAUUUUUGUUAGGAAAACUA-5'(SEQ ID NO:2592)
KRAS-2279靶:5'-AATAAAAATAAAAACAATCCTTTTGAT-3'(SEQ ID NO:3998)
5'-AAAAAUAAAAACAAUCCUUUUGAta-3'(SEQ ID NO:3296)
3'-UAUUUUUAUUUUUGUUAGGAAAACUAU-5'(SEQ ID NO:2593)
KRAS-2280靶:5'-ATAAAAATAAAAACAATCCTTTTGATA-3'(SEQ ID NO:3999)
5'-AAAAUAAAAACAAUCCUUUUGAUaa-3'(SEQ ID NO:3297)
3'-AUUUUUAUUUUUGUUAGGAAAACUAUU-5'(SEQ ID NO:2594)
KRAS-2281靶:5'-TAAAAATAAAAACAATCCTTTTGATAA-3'(SEQ ID NO:4000)
5'-AAAUAAAAACAAUCCUUUUGAUAaa-3'(SEQ ID NO:3298)
3'-UUUUUAUUUUUGUUAGGAAAACUAUUU-5'(SEQ ID NO:2595)
KRAS-2282靶:5'-AAAAATAAAAACAATCCTTTTGATAAA-3'(SEQ ID NO:4001)
5'-AAUAAAAACAAUCCUUUUGAUAAat-3'(SEQ ID NO:3299)
3'-UUUUAUUUUUGUUAGGAAAACUAUUUA-5'(SEQ ID NO:2596)
KRAS-2283靶:5'-AAAATAAAAACAATCCTTTTGATAAAT-3'(SEQ ID NO:4002)
5'-AUAAAAACAAUCCUUUUGAUAAAtt-3'(SEQ ID NO:3300)
3'-UUUAUUUUUGUUAGGAAAACUAUUUAA-5'(SEQ ID NO:2597)
KRAS-2284靶:5'-AAATAAAAACAATCCTTTTGATAAATT-3'(SEQ ID NO:4003)
5'-UAAAAACAAUCCUUUUGAUAAAUtt-3'(SEQ ID NO:3301)
3'-UUAUUUUUGUUAGGAAAACUAUUUAAA-5'(SEQ ID NO:2598)
KRAS-2285靶:5'-AATAAAAACAATCCTTTTGATAAATTT-3'(SEQ ID NO:4004)
5'-AACAAUCCUUUUGAUAAAUUUAAaa-3'(SEQ ID NO:3302)
3'-UUUUGUUAGGAAAACUAUUUAAAUUUU-5'(SEQ ID NO:2599)
KRAS-2289靶:5'-AAAACAATCCTTTTGATAAATTTAAAA-3'(SEQ ID NO:4005)
5'-UCCUUUUGAUAAAUUUAAAAUGUta-3'(SEQ ID NO:3303)
3'-UUAGGAAAACUAUUUAAAUUUUACAAU-5'(SEQ ID NO:2600)
KRAS-2294靶:5'-AATCCTTTTGATAAATTTAAAATGTTA-3'(SEQ ID NO:4006)
5'-CCUUUUGAUAAAUUUAAAAUGUUac-3'(SEQ ID NO:3304)
3'-UAGGAAAACUAUUUAAAUUUUACAAUG-5'(SEQ ID NO:2601)
KRAS-2295靶:5'-ATCCTTTTGATAAATTTAAAATGTTAC-3'(SEQ ID NO:4007)
5'-CUUUUGAUAAAUUUAAAAUGUUAct-3'(SEQ ID NO:3305)
3'-AGGAAAACUAUUUAAAUUUUACAAUGA-5'(SEQ ID NO:2602)
KRAS-2296靶:5'-TCCTTTTGATAAATTTAAAATGTTACT-3'(SEQ ID NO:4008)
5'-UGAUAAAUUUAAAAUGUUACUUAtt-3'(SEQ ID NO:3306)
3'-AAACUAUUUAAAUUUUACAAUGAAUAA-5'(SEQ ID NO:2603)
KRAS-2300靶:5'-TTTGATAAATTTAAAATGTTACTTATT-3'(SEQ ID NO:4009)
5'-GAUAAAUUUAAAAUGUUACUUAUtt-3'(SEQ ID NO:3307)
3'-AACUAUUUAAAUUUUACAAUGAAUAAA-5'(SEQ ID NO:2604)
KRAS-2301靶:5'-TTGATAAATTTAAAATGTTACTTATTT-3'(SEQ ID NO:4010)
5'-AUAAAUUUAAAAUGUUACUUAUUtt-3'(SEQ ID NO:3308)
3'-ACUAUUUAAAUUUUACAAUGAAUAAAA-5'(SEQ ID NO:2605)
KRAS-2302靶:5'-TGATAAATTTAAAATGTTACTTATTTT-3'(SEQ ID NO:4011)
5'-UAAAUUUAAAAUGUUACUUAUUUta-3'(SEQ ID NO:3309)
3'-CUAUUUAAAUUUUACAAUGAAUAAAAU-5'(SEQ ID NO:2606)
KRAS-2303靶:5'-GATAAATTTAAAATGTTACTTATTTTA-3'(SEQ ID NO:4012)
5'-AAAUUUAAAAUGUUACUUAUUUUaa-3'(SEQ ID NO:3310)
3'-UAUUUAAAUUUUACAAUGAAUAAAAUU-5'(SEQ ID NO:2607)
KRAS-2304靶:5'-ATAAATTTAAAATGTTACTTATTTTAA-3'(SEQ ID NO:4013)
5'-AAUUUAAAAUGUUACUUAUUUUAaa-3'(SEQ ID NO:3311)
3'-AUUUAAAUUUUACAAUGAAUAAAAUUU-5'(SEQ ID NO:2608)
KRAS-2305靶:5'-TAAATTTAAAATGTTACTTATTTTAAA-3'(SEQ ID NO:4014)
5'-UUUAAAAUGUUACUUAUUUUAAAat-3'(SEQ ID NO:3312)
3'-UUAAAUUUUACAAUGAAUAAAAUUUUA-5'(SEQ ID NO:2609)
KRAS-2307靶:5'-AATTTAAAATGTTACTTATTTTAAAAT-3'(SEQ ID NO:4015)
5'-UUAAAAUGUUACUUAUUUUAAAAta-3'(SEQ ID NO:3313)
3'-UAAAUUUUACAAUGAAUAAAAUUUUAU-5'(SEQ ID NO:2610)
KRAS-2308靶:5'-ATTTAAAATGTTACTTATTTTAAAATA-3'(SEQ ID NO:4016)
5'-UAAAAUGUUACUUAUUUUAAAAUaa-3'(SEQ ID NO:3314)
3'-AAAUUUUACAAUGAAUAAAAUUUUAUU-5'(SEQ ID NO:2611)
KRAS-2309靶:5'-TTTAAAATGTTACTTATTTTAAAATAA-3'(SEQ ID NO:4017)
5'-AAAAUGUUACUUAUUUUAAAAUAaa-3'(SEQ ID NO:3315)
3'-AAUUUUACAAUGAAUAAAAUUUUAUUU-5'(SEQ ID NO:2612)
KRAS-2310靶:5'-TTAAAATGTTACTTATTTTAAAATAAA-3'(SEQ ID NO:4018)
5'-AAAUGUUACUUAUUUUAAAAUAAat-3'(SEQ ID NO:3316)
3'-AUUUUACAAUGAAUAAAAUUUUAUUUA-5'(SEQ ID NO:2613)
KRAS-2311靶:5'-TAAAATGTTACTTATTTTAAAATAAAT-3'(SEQ ID NO:4019)
5'-AUGUUACUUAUUUUAAAAUAAAUga-3'(SEQ ID NO:3317)
3'-UUUACAAUGAAUAAAAUUUUAUUUACU-5'(SEQ ID NO:2614)
KRAS-2313靶:5'-AAATGTTACTTATTTTAAAATAAATGA-3'(SEQ ID NO:4020)
5'-ACUUAUUUUAAAAUAAAUGAAGUga-3'(SEQ ID NO:3318)
3'-AAUGAAUAAAAUUUUAUUUACUUCACU-5'(SEQ ID NO:2615)
KRAS-2318靶:5'-TTACTTATTTTAAAATAAATGAAGTGA-3'(SEQ ID NO:4021)
5'-UUAUUUUAAAAUAAAUGAAGUGAga-3'(SEQ ID NO:3319)
3'-UGAAUAAAAUUUUAUUUACUUCACUCU-5'(SEQ ID NO:2616)
KRAS-2320靶:5'-ACTTATTTTAAAATAAATGAAGTGAGA-3'(SEQ ID NO:4022)
5'-UAUUUUAAAAUAAAUGAAGUGAGat-3'(SEQ ID NO:3320)
3'-GAAUAAAAUUUUAUUUACUUCACUCUA-5'(SEQ ID NO:2617)
KRAS-2321靶:5'-CTTATTTTAAAATAAATGAAGTGAGAT-3'(SEQ ID NO:4023)
5'-UUUAAAAUAAAUGAAGUGAGAUGgc-3'(SEQ ID NO:3321)
3'-UAAAAUUUUAUUUACUUCACUCUACCG-5'(SEQ ID NO:2618)
KRAS-2324靶:5'-ATTTTAAAATAAATGAAGTGAGATGGC-3'(SEQ ID NO:4024)
5'-UUAAAAUAAAUGAAGUGAGAUGGca-3'(SEQ ID NO:3322)
3'-AAAAUUUUAUUUACUUCACUCUACCGU-5'(SEQ ID NO:2619)
KRAS-2325靶:5'-TTTTAAAATAAATGAAGTGAGATGGCA-3'(SEQ ID NO:4025)
5'-UCCAUUUCUUCAUGUUAAAAGAAgt-3'(SEQ ID NO:3323)
3'-AUAGGUAAAGAAGUACAAUUUUCUUCA-5'(SEQ ID NO:2620)
KRAS-2445靶:5'-TATCCATTTCTTCATGTTAAAAGAAGT-3'(SEQ ID NO:4026)
5'-CCAUUUCUUCAUGUUAAAAGAAGtc-3'(SEQ ID NO:3324)
3'-UAGGUAAAGAAGUACAAUUUUCUUCAG-5'(SEQ ID NO:2621)
KRAS-2446靶:5'-ATCCATTTCTTCATGTTAAAAGAAGTC-3'(SEQ ID NO:4027)
5'-CUCAAACUCUUAGUUUUUUUUUUtt-3'(SEQ ID NO:3325)
3'-UAGAGUUUGAGAAUCAAAAAAAAAAAA-5'(SEQ ID NO:2622)
KRAS-2473靶:5'-ATCTCAAACTCTTAGTTTTTTTTTTTT-3'(SEQ ID NO:4028)
5'-UAGUUUUUUUUUUUUACAACUAUgt-3'(SEQ ID NO:3326)
3'-GAAUCAAAAAAAAAAAAUGUUGAUACA-5'(SEQ ID NO:2623)
KRAS-2483靶:5'-CTTAGTTTTTTTTTTTTACAACTATGT-3'(SEQ ID NO:4029)
5'-AGUUUUUUUUUUUUACAACUAUGta-3'(SEQ ID NO:3327)
3'-AAUCAAAAAAAAAAAAUGUUGAUACAU-5'(SEQ ID NO:2624)
KRAS-2484靶:5'-TTAGTTTTTTTTTTTTACAACTATGTA-3'(SEQ ID NO:4030)
5'-GUUUUUUUUUUUUACAACUAUGUaa-3'(SEQ ID NO:3328)
3'-AUCAAAAAAAAAAAAUGUUGAUACAUU-5'(SEQ ID NO:2625)
KRAS-2485靶:5'-TAGTTTTTTTTTTTTACAACTATGTAA-3'(SEQ ID NO:4031)
5'-UUUUUUUUUUUUACAACUAUGUAat-3'(SEQ ID NO:3329)
3'-UCAAAAAAAAAAAAUGUUGAUACAUUA-5'(SEQ ID NO:2626)
KRAS-2486靶:5'-AGTTTTTTTTTTTTACAACTATGTAAT-3'(SEQ ID NO:4032)
5'-UUUUUUUUUUUACAACUAUGUAAtt-3'(SEQ ID NO:3330)
3'-CAAAAAAAAAAAAUGUUGAUACAUUAA-5'(SEQ ID NO:2627)
KRAS-2487靶:5'-GTTTTTTTTTTTTACAACTATGTAATT-3'(SEQ ID NO:4033)
5'-UUUUUUUUUUACAACUAUGUAAUtt-3'(SEQ ID NO:3331)
3'-AAAAAAAAAAAAUGUUGAUACAUUAAA-5'(SEQ ID NO:2628)
KRAS-2488靶:5'-TTTTTTTTTTTTACAACTATGTAATTT-3'(SEQ ID NO:4034)
5'-UUUUUUUUUACAACUAUGUAAUUta-3'(SEQ ID NO:3332)
3'-AAAAAAAAAAAUGUUGAUACAUUAAAU-5'(SEQ ID NO:2629)
KRAS-2489靶:5'-TTTTTTTTTTTACAACTATGTAATTTA-3'(SEQ ID NO:4035)
5'-UUUUUUUUACAACUAUGUAAUUUat-3'(SEQ ID NO:3333)
3'-AAAAAAAAAAUGUUGAUACAUUAAAUA-5'(SEQ ID NO:2630)
KRAS-2490靶:5'-TTTTTTTTTTACAACTATGTAATTTAT-3'(SEQ ID NO:4036)
5'-UUUUUUUACAACUAUGUAAUUUAta-3'(SEQ ID NO:3334)
3'-AAAAAAAAAUGUUGAUACAUUAAAUAU-5'(SEQ ID NO:2631)
KRAS-2491靶:5'-TTTTTTTTTACAACTATGTAATTTATA-3'(SEQ ID NO:4037)
5'-UUUUUUACAACUAUGUAAUUUAUat-3'(SEQ ID NO:3335)
3'-AAAAAAAAUGUUGAUACAUUAAAUAUA-5'(SEQ ID NO:2632)
KRAS-2492靶:5'-TTTTTTTTACAACTATGTAATTTATAT-3'(SEQ ID NO:4038)
5'-UUUUUACAACUAUGUAAUUUAUAtt-3'(SEQ ID NO:3336)
3'-AAAAAAAUGUUGAUACAUUAAAUAUAA-5'(SEQ ID NO:2633)
KRAS-2493靶:5'-TTTTTTTACAACTATGTAATTTATATT-3'(SEQ ID NO:4039)
5'-AACUAUGUAAUUUAUAUUCCAUUta-3'(SEQ ID NO:3337)
3'-UGUUGAUACAUUAAAUAUAAGGUAAAU-5'(SEQ ID NO:2634)
KRAS-2500靶:5'-ACAACTATGTAATTTATATTCCATTTA-3'(SEQ ID NO:4040)
5'-ACUAUGUAAUUUAUAUUCCAUUUac-3'(SEQ ID NO:3338)
3'-GUUGAUACAUUAAAUAUAAGGUAAAUG-5'(SEQ ID NO:2635)
KRAS-2501靶:5'-CAACTATGTAATTTATATTCCATTTAC-3'(SEQ ID NO:4041)
5'-CUAUGUAAUUUAUAUUCCAUUUAca-3'(SEQ ID NO:3339)
3'-UUGAUACAUUAAAUAUAAGGUAAAUGU-5'(SEQ ID NO:2636)
KRAS-2502靶:5'-AACTATGTAATTTATATTCCATTTACA-3'(SEQ ID NO:4042)
5'-AAUUUAUAUUCCAUUUACAUAAGga-3'(SEQ ID NO:3340)
3'-CAUUAAAUAUAAGGUAAAUGUAUUCCU-5'(SEQ ID NO:2637)
KRAS-2508靶:5'-GTAATTTATATTCCATTTACATAAGGA-3'(SEQ ID NO:4043)
5'-AUUUAUAUUCCAUUUACAUAAGGat-3'(SEQ ID NO:3341)
3'-AUUAAAUAUAAGGUAAAUGUAUUCCUA-5'(SEQ ID NO:2638)
KRAS-2509靶:5'-TAATTTATATTCCATTTACATAAGGAT-3'(SEQ ID NO:4044)
5'-UUUAUAUUCCAUUUACAUAAGGAta-3'(SEQ ID NO:3342)
3'-UUAAAUAUAAGGUAAAUGUAUUCCUAU-5'(SEQ ID NO:2639)
KRAS-2510靶:5'-AATTTATATTCCATTTACATAAGGATA-3'(SEQ ID NO:4045)
5'-UUAUAUUCCAUUUACAUAAGGAUac-3'(SEQ ID NO:3343)
3'-UAAAUAUAAGGUAAAUGUAUUCCUAUG-5'(SEQ ID NO:2640)
KRAS-2511靶:5'-ATTTATATTCCATTTACATAAGGATAC-3'(SEQ ID NO:4046)
5'-UACAUAAGGAUACACUUAUUUGUca-3'(SEQ ID NO:3344)
3'-AAAUGUAUUCCUAUGUGAAUAAACAGU-5'(SEQ ID NO:2641)
KRAS-2523靶:5'-TTTACATAAGGATACACTTATTTGTCA-3'(SEQ ID NO:4047)
5'-UAAGGAUACACUUAUUUGUCAAGct-3'(SEQ ID NO:3345)
3'-GUAUUCCUAUGUGAAUAAACAGUUCGA-5'(SEQ ID NO:2642)
KRAS-2527靶:5'-CATAAGGATACACTTATTTGTCAAGCT-3'(SEQ ID NO:4048)
5'-AUCUGUAAAUUUUUAACCUAUGUta-3'(SEQ ID NO:3346)
3'-GUUAGACAUUUAAAAAUUGGAUACAAU-5'(SEQ ID NO:2643)
KRAS-2559靶:5'-CAATCTGTAAATTTTTAACCTATGTTA-3'(SEQ ID NO:4049)
5'-UCUGUAAAUUUUUAACCUAUGUUac-3'(SEQ ID NO:3347)
3'-UUAGACAUUUAAAAAUUGGAUACAAUG-5'(SEQ ID NO:2644)
KRAS-2560靶:5'-AATCTGTAAATTTTTAACCTATGTTAC-3'(SEQ ID NO:4050)
5'-CUGUAAAUUUUUAACCUAUGUUAca-3'(SEQ ID NO:3348)
3'-UAGACAUUUAAAAAUUGGAUACAAUGU-5'(SEQ ID NO:2645)
KRAS-2561靶:5'-ATCTGTAAATTTTTAACCTATGTTACA-3'(SEQ ID NO:4051)
5'-UGCAAGAGGUGAAGUUUAUAUUUga-3'(SEQ ID NO:3349)
3'-ACACGUUCUCCACUUCAAAUAUAAACU-5'(SEQ ID NO:2646)
KRAS-2617靶:5'-TGTGCAAGAGGTGAAGTTTATATTTGA-3'(SEQ ID NO:4052)
5'-CAAGAGGUGAAGUUUAUAUUUGAat-3'(SEQ ID NO:3350)
3'-ACGUUCUCCACUUCAAAUAUAAACUUA-5'(SEQ ID NO:2647)
KRAS-2619靶:5'-TGCAAGAGGTGAAGTTTATATTTGAAT-3'(SEQ ID NO:4053)
5'-AAGAGGUGAAGUUUAUAUUUGAAta-3'(SEQ ID NO:3351)
3'-CGUUCUCCACUUCAAAUAUAAACUUAU-5'(SEQ ID NO:2648)
KRAS-2620靶:5'-GCAAGAGGTGAAGTTTATATTTGAATA-3'(SEQ ID NO:4054)
5'-GAGGUGAAGUUUAUAUUUGAAUAtc-3'(SEQ ID NO:3352)
3'-UUCUCCACUUCAAAUAUAAACUUAUAG-5'(SEQ ID NO:2649)
KRAS-2622靶:5'-AAGAGGTGAAGTTTATATTTGAATATC-3'(SEQ ID NO:4055)
5'-AGGUGAAGUUUAUAUUUGAAUAUcc-3'(SEQ ID NO:3353)
3'-UCUCCACUUCAAAUAUAAACUUAUAGG-5'(SEQ ID NO:2650)
KRAS-2623靶:5'-AGAGGTGAAGTTTATATTTGAATATCC-3'(SEQ ID NO:4056)
5'-AAGUUUAUAUUUGAAUAUCCAUUct-3'(SEQ ID NO:3354)
3'-ACUUCAAAUAUAAACUUAUAGGUAAGA-5'(SEQ ID NO:2651)
KRAS-2628靶:5'-TGAAGTTTATATTTGAATATCCATTCT-3'(SEQ ID NO:4057)
5'-ACUUGAUGCAGUUUUAAUACUUGta-3'(SEQ ID NO:3355)
3'-ACUGAACUACGUCAAAAUUAUGAACAU-5'(SEQ ID NO:2652)
KRAS-2716靶:5'-TGACTTGATGCAGTTTTAATACTTGTA-3'(SEQ ID NO:4058)
5'-UUGAUGCAGUUUUAAUACUUGUAat-3'(SEQ ID NO:3356)
3'-UGAACUACGUCAAAAUUAUGAACAUUA-5'(SEQ ID NO:2653)
KRAS-2718靶:5'-ACTTGATGCAGTTTTAATACTTGTAAT-3'(SEQ ID NO:4059)
5'-GAUUUGACCUAAUCACUAAUUUUca-3'(SEQ ID NO:3357)
3'-CCCUAAACUGGAUUAGUGAUUAAAAGU-5'(SEQ ID NO:2654)
KRAS-2869靶:5'-GGGATTTGACCTAATCACTAATTTTCA-3'(SEQ ID NO:4060)
5'-ACCUAAUCACUAAUUUUCAGGUGgt-3'(SEQ ID NO:3358)
3'-ACUGGAUUAGUGAUUAAAAGUCCACCA-5'(SEQ ID NO:2655)
KRAS-2875靶:5'-TGACCTAATCACTAATTTTCAGGTGGT-3'(SEQ ID NO:4061)
5'-CAGUAGGAUUUUUCAAACCUGGUat-3'(SEQ ID NO:3359)
3'-CUGUCAUCCUAAAAAGUUUGGACCAUA-5'(SEQ ID NO:2656)
KRAS-2944靶:5'-GACAGTAGGATTTTTCAAACCTGGTAT-3'(SEQ ID NO:4062)
5'-AGUGGAAGGAGAAUUUAAUAAAGat-3'(SEQ ID NO:3360)
3'-GGUCACCUUCCUCUUAAAUUAUUUCUA-5'(SEQ ID NO:2657)
KRAS-2989靶:5'-CCAGTGGAAGGAGAATTTAATAAAGAT-3'(SEQ ID NO:4063)
5'-GGAAGGAGAAUUUAAUAAAGAUAgt-3'(SEQ ID NO:3361)
3'-CACCUUCCUCUUAAAUUAUUUCUAUCA-5'(SEQ ID NO:2658)
KRAS-2992靶:5'-GTGGAAGGAGAATTTAATAAAGATAGT-3'(SEQ ID NO:4064)
5'-AAGGAGAAUUUAAUAAAGAUAGUgc-3'(SEQ ID NO:3362)
3'-CCUUCCUCUUAAAUUAUUUCUAUCACG-5'(SEQ ID NO:2659)
KRAS-2994靶:5'-GGAAGGAGAATTTAATAAAGATAGTGC-3'(SEQ ID NO:4065)
5'-AGGAGAAUUUAAUAAAGAUAGUGct-3'(SEQ ID NO:3363)
3'-CUUCCUCUUAAAUUAUUUCUAUCACGA-5'(SEQ ID NO:2660)
KRAS-2995靶:5'-GAAGGAGAATTTAATAAAGATAGTGCT-3'(SEQ ID NO:4066)
5'-GAAUUUAAUAAAGAUAGUGCUGAaa-3'(SEQ ID NO:3364)
3'-CUCUUAAAUUAUUUCUAUCACGACUUU-5'(SEQ ID NO:2661)
KRAS-2999靶:5'-GAGAATTTAATAAAGATAGTGCTGAAA-3'(SEQ ID NO:4067)
5'-UCCUUAGGUAAUCUAUAACUAGGac-3'(SEQ ID NO:3365)
3'-UAAGGAAUCCAUUAGAUAUUGAUCCUG-5'(SEQ ID NO:2662)
KRAS-3028靶:5'-ATTCCTTAGGTAATCTATAACTAGGAC-3'(SEQ ID NO:4068)
5'-CCUUAGGUAAUCUAUAACUAGGAct-3'(SEQ ID NO:3366)
3'-AAGGAAUCCAUUAGAUAUUGAUCCUGA-5'(SEQ ID NO:2663)
KRAS-3029靶:5'-TTCCTTAGGTAATCTATAACTAGGACT-3'(SEQ ID NO:4069)
5'-AACAGUAAUACAUUCCAUUGUUUta-3'(SEQ ID NO:3367)
3'-CAUUGUCAUUAUGUAAGGUAACAAAAU-5'(SEQ ID NO:2664)
KRAS-3063靶:5'-GTAACAGTAATACATTCCATTGTTTTA-3'(SEQ ID NO:4070)
5'-CAGUAAUACAUUCCAUUGUUUUAgt-3'(SEQ ID NO:3368)
3'-UUGUCAUUAUGUAAGGUAACAAAAUCA-5'(SEQ ID NO:2665)
KRAS-3065靶:5'-AACAGTAATACATTCCATTGTTTTAGT-3'(SEQ ID NO:4071)
5'-AGUAAUACAUUCCAUUGUUUUAGta-3'(SEQ ID NO:3369)
3'-UGUCAUUAUGUAAGGUAACAAAAUCAU-5'(SEQ ID NO:2666)
KRAS-3066靶:5'-ACAGTAATACATTCCATTGTTTTAGTA-3'(SEQ ID NO:4072)
5'-GUAAUACAUUCCAUUGUUUUAGUaa-3'(SEQ ID NO:3370)
3'-GUCAUUAUGUAAGGUAACAAAAUCAUU-5'(SEQ ID NO:2667)
KRAS-3067靶:5'-CAGTAATACATTCCATTGTTTTAGTAA-3'(SEQ ID NO:4073)
5'-CCAUUGUUUUAGUAACCAGAAAUct-3'(SEQ ID NO:3371)
3'-AAGGUAACAAAAUCAUUGGUCUUUAGA-5'(SEQ ID NO:2668)
KRAS-3077靶:5'-TTCCATTGTTTTAGTAACCAGAAATCT-3'(SEQ ID NO:4074)
5'-ACCAGAAAUCUUCAUGCAAUGAAaa-3'(SEQ ID NO:3372)
3'-AUUGGUCUUUAGAAGUACGUUACUUUU-5'(SEQ ID NO:2669)
KRAS-3091靶:5'-TAACCAGAAATCTTCATGCAATGAAAA-3'(SEQ ID NO:4075)
5'-UUCAUGCAAUGAAAAAUACUUUAat-3'(SEQ ID NO:3373)
3'-AGAAGUACGUUACUUUUUAUGAAAUUA-5'(SEQ ID NO:2670)
KRAS-3101靶:5'-TCTTCATGCAATGAAAAATACTTTAAT-3'(SEQ ID NO:4076)
5'-AAUGAAAAAUACUUUAAUUCAUGaa-3'(SEQ ID NO:3374)
3'-CGUUACUUUUUAUGAAAUUAAGUACUU-5'(SEQ ID NO:2671)
KRAS-3108靶:5'-GCAATGAAAAATACTTTAATTCATGAA-3'(SEQ ID NO:4077)
5'-UGAAAAAUACUUUAAUUCAUGAAgc-3'(SEQ ID NO:3375)
3'-UUACUUUUUAUGAAAUUAAGUACUUCG-5'(SEQ ID NO:2672)
KRAS-3110靶:5'-AATGAAAAATACTTTAATTCATGAAGC-3'(SEQ ID NO:4078)
5'-GAAAAAUACUUUAAUUCAUGAAGct-3'(SEQ ID NO:3376)
3'-UACUUUUUAUGAAAUUAAGUACUUCGA-5'(SEQ ID NO:2673)
KRAS-3111靶:5'-ATGAAAAATACTTTAATTCATGAAGCT-3'(SEQ ID NO:4079)
5'-UUCAUGAAGCUUACUUUUUUUUUtt-3'(SEQ ID NO:3377)
3'-UUAAGUACUUCGAAUGAAAAAAAAAAA-5'(SEQ ID NO:2674)
KRAS-3125靶:5'-AATTCATGAAGCTTACTTTTTTTTTTT-3'(SEQ ID NO:4080)
5'-AUGAAGCUUACUUUUUUUUUUUGgt-3'(SEQ ID NO:3378)
3'-AGUACUUCGAAUGAAAAAAAAAAACCA-5'(SEQ ID NO:2675)
KRAS-3128靶:5'-TCATGAAGCTTACTTTTTTTTTTTGGT-3'(SEQ ID NO:4081)
5'-AGCUUACUUUUUUUUUUUGGUGUca-3'(SEQ ID NO:3379)
3'-CUUCGAAUGAAAAAAAAAAACCACAGU-5'(SEQ ID NO:2676)
KRAS-3132靶:5'-GAAGCTTACTTTTTTTTTTTGGTGTCA-3'(SEQ ID NO:4082)
5'-UACUUUUUUUUUUUGGUGUCAGAgt-3'(SEQ ID NO:3380)
3'-GAAUGAAAAAAAAAAACCACAGUCUCA-5'(SEQ ID NO:2677)
KRAS-3136靶:5'-CTTACTTTTTTTTTTTGGTGTCAGAGT-3'(SEQ ID NO:4083)
5'-ACUUUUUUUUUUUGGUGUCAGAGtc-3'(SEQ ID NO:3381)
3'-AAUGAAAAAAAAAAACCACAGUCUCAG-5'(SEQ ID NO:2678)
KRAS-3137靶:5'-TTACTTTTTTTTTTTGGTGTCAGAGTC-3'(SEQ ID NO:4084)
5'-AACUAAUUUUUGUAUUUUUAGGAga-3'(SEQ ID NO:3382)
3'-AGUUGAUUAAAAACAUAAAAAUCCUCU-5'(SEQ ID NO:2679)
KRAS-3295靶:5'-TCAACTAATTTTTGTATTTTTAGGAGA-3'(SEQ ID NO:4085)
5'-UAAUUUUUGUAUUUUUAGGAGAGac-3'(SEQ ID NO:3383)
3'-UGAUUAAAAACAUAAAAAUCCUCUCUG-5'(SEQ ID NO:2680)
KRAS-3298靶:5'-ACTAATTTTTGTATTTTTAGGAGAGAC-3'(SEQ ID NO:4086)
5'-CUCAUUUAUUCAGCAAAUAUUUAtt-3'(SEQ ID NO:3384)
3'-UUGAGUAAAUAAGUCGUUUAUAAAUAA-5'(SEQ ID NO:2681)
KRAS-3411靶:5'-AACTCATTTATTCAGCAAATATTTATT-3'(SEQ ID NO:4087)
5'-CAUUUAUUCAGCAAAUAUUUAUUga-3'(SEQ ID NO:3385)
3'-GAGUAAAUAAGUCGUUUAUAAAUAACU-5'(SEQ ID NO:2682)
KRAS-3413靶:5'-CTCATTTATTCAGCAAATATTTATTGA-3'(SEQ ID NO:4088)
5'-UUUAUUCAGCAAAUAUUUAUUGAgt-3'(SEQ ID NO:3386)
3'-GUAAAUAAGUCGUUUAUAAAUAACUCA-5'(SEQ ID NO:2683)
KRAS-3415靶:5'-CATTTATTCAGCAAATATTTATTGAGT-3'(SEQ ID NO:4089)
5'-UAUUUUAGUUUUGCAAAGAAGGGgt-3'(SEQ ID NO:3387)
3'-GCAUAAAAUCAAAACGUUUCUUCCCCA-5'(SEQ ID NO:2684)
KRAS-3587靶:5'-CGTATTTTAGTTTTGCAAAGAAGGGGT-3'(SEQ ID NO:4090)
5'-CUCUAUAAUUGUUUUGCUACGAUtc-3'(SEQ ID NO:3388)
3'-UCGAGAUAUUAACAAAACGAUGCUAAG-5'(SEQ ID NO:2685)
KRAS-3628靶:5'-AGCTCTATAATTGTTTTGCTACGATTC-3'(SEQ ID NO:4091)
5'-UACUUUAUGUAAAUCACUUCAUUgt-3'(SEQ ID NO:3389)
3'-CGAUGAAAUACAUUUAGUGAAGUAACA-5'(SEQ ID NO:2686)
KRAS-3675靶:5'-GCTACTTTATGTAAATCACTTCATTGT-3'(SEQ ID NO:4092)
5'-ACUUUAUGUAAAUCACUUCAUUGtt-3'(SEQ ID NO:3390)
3'-GAUGAAAUACAUUUAGUGAAGUAACAA-5'(SEQ ID NO:2687)
KRAS-3676靶:5'-CTACTTTATGTAAATCACTTCATTGTT-3'(SEQ ID NO:4093)
5'-CUUUAUGUAAAUCACUUCAUUGUtt-3'(SEQ ID NO:3391)
3'-AUGAAAUACAUUUAGUGAAGUAACAAA-5'(SEQ ID NO:2688)
KRAS-3677靶:5'-TACTTTATGTAAATCACTTCATTGTTT-3'(SEQ ID NO:4094)
5'-UUUAUGUAAAUCACUUCAUUGUUtt-3'(SEQ ID NO:3392)
3'-UGAAAUACAUUUAGUGAAGUAACAAAA-5'(SEQ ID NO:2689)
KRAS-3678靶:5'-ACTTTATGTAAATCACTTCATTGTTTT-3'(SEQ ID NO:4095)
5'-UUAUGUAAAUCACUUCAUUGUUUta-3'(SEQ ID NO:3393)
3'-GAAAUACAUUUAGUGAAGUAACAAAAU-5'(SEQ ID NO:2690)
KRAS-3679靶:5'-CTTTATGTAAATCACTTCATTGTTTTA-3'(SEQ ID NO:4096)
5'-UAUGUAAAUCACUUCAUUGUUUUaa-3'(SEQ ID NO:3394)
3'-AAAUACAUUUAGUGAAGUAACAAAAUU-5'(SEQ ID NO:2691)
KRAS-3680靶:5'-TTTATGTAAATCACTTCATTGTTTTAA-3'(SEQ ID NO:4097)
5'-AUGUAAAUCACUUCAUUGUUUUAaa-3'(SEQ ID NO:3395)
3'-AAUACAUUUAGUGAAGUAACAAAAUUU-5'(SEQ ID NO:2692)
KRAS-3681靶:5'-TTATGTAAATCACTTCATTGTTTTAAA-3'(SEQ ID NO:4098)
5'-AUUGUUUUAAAGGAAUAAACUUGat-3'(SEQ ID NO:3396)
3'-AGUAACAAAAUUUCCUUAUUUGAACUA-5'(SEQ ID NO:2693)
KRAS-3695靶:5'-TCATTGTTTTAAAGGAATAAACTTGAT-3'(SEQ ID NO:4099)
5'-UUGUUUUAAAGGAAUAAACUUGAtt-3'(SEQ ID NO:3397)
3'-GUAACAAAAUUUCCUUAUUUGAACUAA-5'(SEQ ID NO:2694)
KRAS-3696靶:5'-CATTGTTTTAAAGGAATAAACTTGATT-3'(SEQ ID NO:4100)
5'-UUUUAAAGGAAUAAACUUGAUUAta-3'(SEQ ID NO:3398)
3'-ACAAAAUUUCCUUAUUUGAACUAAUAU-5'(SEQ ID NO:2695)
KRAS-3699靶:5'-TGTTTTAAAGGAATAAACTTGATTATA-3'(SEQ ID NO:4101)
5'-UUUAAAGGAAUAAACUUGAUUAUat-3'(SEQ ID NO:3399)
3'-CAAAAUUUCCUUAUUUGAACUAAUAUA-5'(SEQ ID NO:2696)
KRAS-3700靶:5'-GTTTTAAAGGAATAAACTTGATTATAT-3'(SEQ ID NO:4102)
5'-UUAAAGGAAUAAACUUGAUUAUAtt-3'(SEQ ID NO:3400)
3'-AAAAUUUCCUUAUUUGAACUAAUAUAA-5'(SEQ ID NO:2697)
KRAS-3701靶:5'-TTTTAAAGGAATAAACTTGATTATATT-3'(SEQ ID NO:4103)
5'-AAAGGAAUAAACUUGAUUAUAUUgt-3'(SEQ ID NO:3401)
3'-AAUUUCCUUAUUUGAACUAAUAUAACA-5'(SEQ ID NO:2698)
KRAS-3703靶:5'-TTAAAGGAATAAACTTGATTATATTGT-3'(SEQ ID NO:4104)
5'-AAGGAAUAAACUUGAUUAUAUUGtt-3'(SEQ ID NO:3402)
3'-AUUUCCUUAUUUGAACUAAUAUAACAA-5'(SEQ ID NO:2699)
KRAS-3704靶:5'-TAAAGGAATAAACTTGATTATATTGTT-3'(SEQ ID NO:4105)
5'-AGGAAUAAACUUGAUUAUAUUGUtt-3'(SEQ ID NO:3403)
3'-UUUCCUUAUUUGAACUAAUAUAACAAA-5'(SEQ ID NO:2700)
KRAS-3705靶:5'-AAAGGAATAAACTTGATTATATTGTTT-3'(SEQ ID NO:4106)
5'-GGAAUAAACUUGAUUAUAUUGUUtt-3'(SEQ ID NO:3404)
3'-UUCCUUAUUUGAACUAAUAUAACAAAA-5'(SEQ ID NO:2701)
KRAS-3706靶:5'-AAGGAATAAACTTGATTATATTGTTTT-3'(SEQ ID NO:4107)
5'-GAAUAAACUUGAUUAUAUUGUUUtt-3'(SEQ ID NO:3405)
3'-UCCUUAUUUGAACUAAUAUAACAAAAA-5'(SEQ ID NO:2702)
KRAS-3707靶:5'-AGGAATAAACTTGATTATATTGTTTTT-3'(SEQ ID NO:4108)
5'-AACUUGAUUAUAUUGUUUUUUUAtt-3'(SEQ ID NO:3406)
3'-AUUUGAACUAAUAUAACAAAAAAAUAA-5'(SEQ ID NO:2703)
KRAS-3712靶:5'-TAAACTTGATTATATTGTTTTTTTATT-3'(SEQ ID NO:4109)
5'-ACUUGAUUAUAUUGUUUUUUUAUtt-3'(SEQ ID NO:3407)
3'-UUUGAACUAAUAUAACAAAAAAAUAAA-5'(SEQ ID NO:2704)
KRAS-3713靶:5'-AAACTTGATTATATTGTTTTTTTATTT-3'(SEQ ID NO:4110)
5'-UGAUUAUAUUGUUUUUUUAUUUGgc-3'(SEQ ID NO:3408)
3'-GAACUAAUAUAACAAAAAAAUAAACCG-5'(SEQ ID NO:2705)
KRAS-3716靶:5'-CTTGATTATATTGTTTTTTTATTTGGC-3'(SEQ ID NO:4111)
5'-AUAUUGUUUUUUUAUUUGGCAUAac-3'(SEQ ID NO:3409)
3'-AAUAUAACAAAAAAAUAAACCGUAUUG-5'(SEQ ID NO:2706)
KRAS-3721靶:5'-TTATATTGTTTTTTTATTTGGCATAAC-3'(SEQ ID NO:4112)
5'-UAUUGUUUUUUUAUUUGGCAUAAct-3'(SEQ ID NO:3410)
3'-AUAUAACAAAAAAAUAAACCGUAUUGA-5'(SEQ ID NO:2707)
KRAS-3722靶:5'-TATATTGTTTTTTTATTTGGCATAACT-3'(SEQ ID NO:4113)
5'-GUUUUUUUAUUUGGCAUAACUGUga-3'(SEQ ID NO:3411)
3'-AACAAAAAAAUAAACCGUAUUGACACU-5'(SEQ ID NO:2708)
KRAS-3726靶:5'-TTGTTTTTTTATTTGGCATAACTGTGA-3'(SEQ ID NO:4114)
5'-UUUUUUUAUUUGGCAUAACUGUGat-3'(SEQ ID NO:3412)
3'-ACAAAAAAAUAAACCGUAUUGACACUA-5'(SEQ ID NO:2709)
KRAS-3727靶:5'-TGTTTTTTTATTTGGCATAACTGTGAT-3'(SEQ ID NO:4115)
5'-GCAUAACUGUGAUUCUUUUAGGAca-3'(SEQ ID NO:3413)
3'-ACCGUAUUGACACUAAGAAAAUCCUGU-5'(SEQ ID NO:2710)
KRAS-3739靶:5'-TGGCATAACTGTGATTCTTTTAGGACA-3'(SEQ ID NO:4116)
5'-ACUGUGAUUCUUUUAGGACAAUUac-3'(SEQ ID NO:3414)
3'-AUUGACACUAAGAAAAUCCUGUUAAUG-5'(SEQ ID NO:2711)
KRAS-3744靶:5'-TAACTGTGATTCTTTTAGGACAATTAC-3'(SEQ ID NO:4117)
5'-CUGUGAUUCUUUUAGGACAAUUAct-3'(SEQ ID NO:3415)
3'-UUGACACUAAGAAAAUCCUGUUAAUGA-5'(SEQ ID NO:2712)
KRAS-3745靶:5'-AACTGTGATTCTTTTAGGACAATTACT-3'(SEQ ID NO:4118)
5'-GGUGUAUGUCAGAUAUUCAUAUUga-3'(SEQ ID NO:3416)
3'-UUCCACAUACAGUCUAUAAGUAUAACU-5'(SEQ ID NO:2713)
KRAS-3781靶:5'-AAGGTGTATGTCAGATATTCATATTGA-3'(SEQ ID NO:4119)
5'-GUGUAUGUCAGAUAUUCAUAUUGac-3'(SEQ ID NO:3417)
3'-UCCACAUACAGUCUAUAAGUAUAACUG-5'(SEQ ID NO:2714)
KRAS-3782靶:5'-AGGTGTATGTCAGATATTCATATTGAC-3'(SEQ ID NO:4120)
5'-CAAAUGUGUAAUAUUCCAGUUUUct-3'(SEQ ID NO:3418)
3'-GGGUUUACACAUUAUAAGGUCAAAAGA-5'(SEQ ID NO:2715)
KRAS-3808靶:5'-CCCAAATGTGTAATATTCCAGTTTTCT-3'(SEQ ID NO:4121)
5'-CAUAAGUAAUUAAAAUAUACUUAaa-3'(SEQ ID NO:3419)
3'-ACGUAUUCAUUAAUUUUAUAUGAAUUU-5'(SEQ ID NO:2716)
KRAS-3836靶:5'-TGCATAAGTAATTAAAATATACTTAAA-3'(SEQ ID NO:4122)
5'-AUAAGUAAUUAAAAUAUACUUAAaa-3'(SEQ ID NO:3420)
3'-CGUAUUCAUUAAUUUUAUAUGAAUUUU-5'(SEQ ID NO:2717)
KRAS-3837靶:5'-GCATAAGTAATTAAAATATACTTAAAA-3'(SEQ ID NO:4123)
5'-UAAGUAAUUAAAAUAUACUUAAAaa-3'(SEQ ID NO:3421)
3'-GUAUUCAUUAAUUUUAUAUGAAUUUUU-5'(SEQ ID NO:2718)
KRAS-3838靶:5'-CATAAGTAATTAAAATATACTTAAAAA-3'(SEQ ID NO:4124)
5'-AAGUAAUUAAAAUAUACUUAAAAat-3'(SEQ ID NO:3422)
3'-UAUUCAUUAAUUUUAUAUGAAUUUUUA-5'(SEQ ID NO:2719)
KRAS-3839靶:5'-ATAAGTAATTAAAATATACTTAAAAAT-3'(SEQ ID NO:4125)
5'-AGUAAUUAAAAUAUACUUAAAAAtt-3'(SEQ ID NO:3423)
3'-AUUCAUUAAUUUUAUAUGAAUUUUUAA-5'(SEQ ID NO:2720)
KRAS-3840靶:5'-TAAGTAATTAAAATATACTTAAAAATT-3'(SEQ ID NO:4126)
5'-GUAAUUAAAAUAUACUUAAAAAUta-3'(SEQ ID NO:3424)
3'-UUCAUUAAUUUUAUAUGAAUUUUUAAU-5'(SEQ ID NO:2721)
KRAS-3841靶:5'-AAGTAATTAAAATATACTTAAAAATTA-3'(SEQ ID NO:4127)
5'-UAAUUAAAAUAUACUUAAAAAUUaa-3'(SEQ ID NO:3425)
3'-UCAUUAAUUUUAUAUGAAUUUUUAAUU-5'(SEQ ID NO:2722)
KRAS-3842靶:5'-AGTAATTAAAATATACTTAAAAATTAA-3'(SEQ ID NO:4128)
5'-AAUUAAAAUAUACUUAAAAAUUAat-3'(SEQ ID NO:3426)
3'-CAUUAAUUUUAUAUGAAUUUUUAAUUA-5'(SEQ ID NO:2723)
KRAS-3843靶:5'-GTAATTAAAATATACTTAAAAATTAAT-3'(SEQ ID NO:4129)
5'-AUUAAAAUAUACUUAAAAAUUAAta-3'(SEQ ID NO:3427)
3'-AUUAAUUUUAUAUGAAUUUUUAAUUAU-5'(SEQ ID NO:2724)
KRAS-3844靶:5'-TAATTAAAATATACTTAAAAATTAATA-3'(SEQ ID NO:4130)
5'-UAAAAUAUACUUAAAAAUUAAUAgt-3'(SEQ ID NO:3428)
3'-UAAUUUUAUAUGAAUUUUUAAUUAUCA-5'(SEQ ID NO:2725)
KRAS-3846靶:5'-ATTAAAATATACTTAAAAATTAATAGT-3'(SEQ ID NO:4131)
5'-AAAAUAUACUUAAAAAUUAAUAGtt-3'(SEQ ID NO:3429)
3'-AAUUUUAUAUGAAUUUUUAAUUAUCAA-5'(SEQ ID NO:2726)
KRAS-3847靶:5'-TTAAAATATACTTAAAAATTAATAGTT-3'(SEQ ID NO:4132)
5'-AAAUAUACUUAAAAAUUAAUAGUtt-3'(SEQ ID NO:3430)
3'-AUUUUAUAUGAAUUUUUAAUUAUCAAA-5'(SEQ ID NO:2727)
KRAS-3848靶:5'-TAAAATATACTTAAAAATTAATAGTTT-3'(SEQ ID NO:4133)
5'-AAUAUACUUAAAAAUUAAUAGUUtt-3'(SEQ ID NO:3431)
3'-UUUUAUAUGAAUUUUUAAUUAUCAAAA-5'(SEQ ID NO:2728)
KRAS-3849靶:5'-AAAATATACTTAAAAATTAATAGTTTT-3'(SEQ ID NO:4134)
5'-UACUUAAAAAUUAAUAGUUUUAUct-3'(SEQ ID NO:3432)
3'-AUAUGAAUUUUUAAUUAUCAAAAUAGA-5'(SEQ ID NO:2729)
KRAS-3853靶:5'-TATACTTAAAAATTAATAGTTTTATCT-3'(SEQ ID NO:4135)
5'-UAAAAAUUAAUAGUUUUAUCUGGgt-3'(SEQ ID NO:3433)
3'-GAAUUUUUAAUUAUCAAAAUAGACCCA-5'(SEQ ID NO:2730)
KRAS-3857靶:5'-CTTAAAAATTAATAGTTTTATCTGGGT-3'(SEQ ID NO:4136)
5'-AAAAAUUAAUAGUUUUAUCUGGGta-3'(SEQ ID NO:3434)
3'-AAUUUUUAAUUAUCAAAAUAGACCCAU-5'(SEQ ID NO:2731)
KRAS-3858靶:5'-TTAAAAATTAATAGTTTTATCTGGGTA-3'(SEQ ID NO:4137)
5'-AAAAUUAAUAGUUUUAUCUGGGUac-3'(SEQ ID NO:3435)
3'-AUUUUUAAUUAUCAAAAUAGACCCAUG-5'(SEQ ID NO:2732)
KRAS-3859靶:5'-TAAAAATTAATAGTTTTATCTGGGTAC-3'(SEQ ID NO:4138)
5'-AUCUGGGUACAAAUAAACAGGUGcc-3'(SEQ ID NO:3436)
3'-AAUAGACCCAUGUUUAUUUGUCCACGG-5'(SEQ ID NO:2733)
KRAS-3874靶:5'-TTATCTGGGTACAAATAAACAGGTGCC-3'(SEQ ID NO:4139)
5'-GACAAGGAAACUUCUAUGUAAAAat-3'(SEQ ID NO:3437)
3'-GUCUGUUCCUUUGAAGAUACAUUUUUA-5'(SEQ ID NO:2734)
KRAS-3913靶:5'-CAGACAAGGAAACTTCTATGTAAAAAT-3'(SEQ ID NO:4140)
5'-ACAAGGAAACUUCUAUGUAAAAAtc-3'(SEQ ID NO:3438)
3'-UCUGUUCCUUUGAAGAUACAUUUUUAG-5'(SEQ ID NO:2735)
KRAS-3914靶:5'-AGACAAGGAAACTTCTATGTAAAAATC-3'(SEQ ID NO:4141)
5'-CAAGGAAACUUCUAUGUAAAAAUca-3'(SEQ ID NO:3439)
3'-CUGUUCCUUUGAAGAUACAUUUUUAGU-5'(SEQ ID NO:2736)
KRAS-3915靶:5'-GACAAGGAAACTTCTATGTAAAAATCA-3'(SEQ ID NO:4142)
5'-UUCUAUGUAAAAAUCACUAUGAUtt-3'(SEQ ID NO:3440)
3'-UGAAGAUACAUUUUUAGUGAUACUAAA-5'(SEQ ID NO:2737)
KRAS-3924靶:5'-ACTTCTATGTAAAAATCACTATGATTT-3'(SEQ ID NO:4143)
5'-UCUAUGUAAAAAUCACUAUGAUUtc-3'(SEQ ID NO:3441)
3'-GAAGAUACAUUUUUAGUGAUACUAAAG-5'(SEQ ID NO:2738)
KRAS-3925靶:5'-CTTCTATGTAAAAATCACTATGATTTC-3'(SEQ ID NO:4144)
5'-CUAUGUAAAAAUCACUAUGAUUUct-3'(SEQ ID NO:3442)
3'-AAGAUACAUUUUUAGUGAUACUAAAGA-5'(SEQ ID NO:2739)
KRAS-3926靶:5'-TTCTATGTAAAAATCACTATGATTTCT-3'(SEQ ID NO:4145)
5'-GUAAAAAUCACUAUGAUUUCUGAat-3'(SEQ ID NO:3443)
3'-UACAUUUUUAGUGAUACUAAAGACUUA-5'(SEQ ID NO:2740)
KRAS-3930靶:5'-ATGTAAAAATCACTATGATTTCTGAAT-3'(SEQ ID NO:4146)
5'-UAAAAAUCACUAUGAUUUCUGAAtt-3'(SEQ ID NO:3444)
3'-ACAUUUUUAGUGAUACUAAAGACUUAA-5'(SEQ ID NO:2741)
KRAS-3931靶:5'-TGTAAAAATCACTATGATTTCTGAATT-3'(SEQ ID NO:4147)
5'-CUAUGAUUUCUGAAUUGCUAUGUga-3'(SEQ ID NO:3445)
3'-GUGAUACUAAAGACUUAACGAUACACU-5'(SEQ ID NO:2742)
KRAS-3940靶:5'-CACTATGATTTCTGAATTGCTATGTGA-3'(SEQ ID NO:4148)
5'-UAUGAUUUCUGAAUUGCUAUGUGaa-3'(SEQ ID NO:3446)
3'-UGAUACUAAAGACUUAACGAUACACUU-5'(SEQ ID NO:2743)
KRAS-3941靶:5'-ACTATGATTTCTGAATTGCTATGTGAA-3'(SEQ ID NO:4149)
5'-UAUGUGAAACUACAGAUCUUUGGaa-3'(SEQ ID NO:3447)
3'-CGAUACACUUUGAUGUCUAGAAACCUU-5'(SEQ ID NO:2744)
KRAS-3958靶:5'-GCTATGTGAAACTACAGATCTTTGGAA-3'(SEQ ID NO:4150)
5'-AUGUGAAACUACAGAUCUUUGGAac-3'(SEQ ID NO:3448)
3'-GAUACACUUUGAUGUCUAGAAACCUUG-5'(SEQ ID NO:2745)
KRAS-3959靶:5'-CTATGTGAAACTACAGATCTTTGGAAC-3'(SEQ ID NO:4151)
5'-AGGGUGUUAAGACUUACACAGUAcc-3'(SEQ ID NO:3449)
3'-CAUCCCACAAUUCUGAAUGUGUCAUGG-5'(SEQ ID NO:2746)
KRAS-3995靶:5'-GTAGGGTGTTAAGACTTACACAGTACC-3'(SEQ ID NO:4152)
5'-UUUAGGCCUCUUGAAUUUUUGAUgt-3'(SEQ ID NO:3450)
3'-AUAAAUCCGGAGAACUUAAAAACUACA-5'(SEQ ID NO:2747)
KRAS-4082靶:5'-TATTTAGGCCTCTTGAATTTTTGATGT-3'(SEQ ID NO:4153)
5'-UCUUGAAUUUUUGAUGUAGAUGGgc-3'(SEQ ID NO:3451)
3'-GGAGAACUUAAAAACUACAUCUACCCG-5'(SEQ ID NO:2748)
KRAS-4090靶:5'-CCTCTTGAATTTTTGATGTAGATGGGC-3'(SEQ ID NO:4154)
5'-CUUGAAUUUUUGAUGUAGAUGGGca-3'(SEQ ID NO:3452)
3'-GAGAACUUAAAAACUACAUCUACCCGU-5'(SEQ ID NO:2749)
KRAS-4091靶:5'-CTCTTGAATTTTTGATGTAGATGGGCA-3'(SEQ ID NO:4155)
5'-UAGAUGGGCAUUUUUUUAAGGUAgt-3'(SEQ ID NO:3453)
3'-ACAUCUACCCGUAAAAAAAUUCCAUCA-5'(SEQ ID NO:2750)
KRAS-4106靶:5'-TGTAGATGGGCATTTTTTTAAGGTAGT-3'(SEQ ID NO:4156)
5'-GGCAUUUUUUUAAGGUAGUGGUUaa-3'(SEQ ID NO:3454)
3'-ACCCGUAAAAAAAUUCCAUCACCAAUU-5'(SEQ ID NO:2751)
KRAS-4112靶:5'-TGGGCATTTTTTTAAGGTAGTGGTTAA-3'(SEQ ID NO:4157)
5'-AGGUAGUGGUUAAUUACCUUUAUgt-3'(SEQ ID NO:3455)
3'-AUUCCAUCACCAAUUAAUGGAAAUACA-5'(SEQ ID NO:2752)
KRAS-4124靶:5'-TAAGGTAGTGGTTAATTACCTTTATGT-3'(SEQ ID NO:4158)
5'-GUAGUGGUUAAUUACCUUUAUGUga-3'(SEQ ID NO:3456)
3'-UCCAUCACCAAUUAAUGGAAAUACACU-5'(SEQ ID NO:2753)
KRAS-4126靶:5'-AGGTAGTGGTTAATTACCTTTATGTGA-3'(SEQ ID NO:4159)
5'-UAGUGGUUAAUUACCUUUAUGUGaa-3'(SEQ ID NO:3457)
3'-CCAUCACCAAUUAAUGGAAAUACACUU-5'(SEQ ID NO:2754)
KRAS-4127靶:5'-GGTAGTGGTTAATTACCTTTATGTGAA-3'(SEQ ID NO:4160)
5'-AGUGGUUAAUUACCUUUAUGUGAac-3'(SEQ ID NO:3458)
3'-CAUCACCAAUUAAUGGAAAUACACUUG-5'(SEQ ID NO:2755)
KRAS-4128靶:5'-GTAGTGGTTAATTACCTTTATGTGAAC-3'(SEQ ID NO:4161)
5'-GUGGUUAAUUACCUUUAUGUGAAct-3'(SEQ ID NO:3459)
3'-AUCACCAAUUAAUGGAAAUACACUUGA-5'(SEQ ID NO:2756)
KRAS-4129靶:5'-TAGTGGTTAATTACCTTTATGTGAACT-3'(SEQ ID NO:4162)
5'-ACCUUUAUGUGAACUUUGAAUGGtt-3'(SEQ ID NO:3460)
3'-AAUGGAAAUACACUUGAAACUUACCAA-5'(SEQ ID NO:2757)
KRAS-4139靶:5'-TTACCTTTATGTGAACTTTGAATGGTT-3'(SEQ ID NO:4163)
5'-UAUGUGAACUUUGAAUGGUUUAAca-3'(SEQ ID NO:3461)
3'-AAAUACACUUGAAACUUACCAAAUUGU-5'(SEQ ID NO:2758)
KRAS-4144靶:5'-TTTATGTGAACTTTGAATGGTTTAACA-3'(SEQ ID NO:4164)
5'-AACUUUGAAUGGUUUAACAAAAGat-3'(SEQ ID NO:3462)
3'-ACUUGAAACUUACCAAAUUGUUUUCUA-5'(SEQ ID NO:2759)
KRAS-4150靶:5'-TGAACTTTGAATGGTTTAACAAAAGAT-3'(SEQ ID NO:4165)
5'-UUGAAUGGUUUAACAAAAGAUUUgt-3'(SEQ ID NO:3463)
3'-GAAACUUACCAAAUUGUUUUCUAAACA-5'(SEQ ID NO:2760)
KRAS-4154靶:5'-CTTTGAATGGTTTAACAAAAGATTTGT-3'(SEQ ID NO:4166)
5'-UGAAUGGUUUAACAAAAGAUUUGtt-3'(SEQ ID NO:3464)
3'-AAACUUACCAAAUUGUUUUCUAAACAA-5'(SEQ ID NO:2761)
KRAS-4155靶:5'-TTTGAATGGTTTAACAAAAGATTTGTT-3'(SEQ ID NO:4167)
5'-GAAUGGUUUAACAAAAGAUUUGUtt-3'(SEQ ID NO:3465)
3'-AACUUACCAAAUUGUUUUCUAAACAAA-5'(SEQ ID NO:2762)
KRAS-4156靶:5'-TTGAATGGTTTAACAAAAGATTTGTTT-3'(SEQ ID NO:4168)
5'-AAUGGUUUAACAAAAGAUUUGUUtt-3'(SEQ ID NO:3466)
3'-ACUUACCAAAUUGUUUUCUAAACAAAA-5'(SEQ ID NO:2763)
KRAS-4157靶:5'-TGAATGGTTTAACAAAAGATTTGTTTT-3'(SEQ ID NO:4169)
5'-AUGGUUUAACAAAAGAUUUGUUUtt-3'(SEQ ID NO:3467)
3'-CUUACCAAAUUGUUUUCUAAACAAAAA-5'(SEQ ID NO:2764)
KRAS-4158靶:5'-GAATGGTTTAACAAAAGATTTGTTTTT-3'(SEQ ID NO:4170)
5'-GGUUUAACAAAAGAUUUGUUUUUgt-3'(SEQ ID NO:3468)
3'-UACCAAAUUGUUUUCUAAACAAAAACA-5'(SEQ ID NO:2765)
KRAS-4160靶:5'-ATGGTTTAACAAAAGATTTGTTTTTGT-3'(SEQ ID NO:4171)
5'-GUUUAACAAAAGAUUUGUUUUUGta-3'(SEQ ID NO:3469)
3'-ACCAAAUUGUUUUCUAAACAAAAACAU-5'(SEQ ID NO:2766)
KRAS-4161靶:5'-TGGTTTAACAAAAGATTTGTTTTTGTA-3'(SEQ ID NO:4172)
5'-AACAAAAGAUUUGUUUUUGUAGAga-3'(SEQ ID NO:3470)
3'-AAUUGUUUUCUAAACAAAAACAUCUCU-5'(SEQ ID NO:2767)
KRAS-4165靶:5'-TTAACAAAAGATTTGTTTTTGTAGAGA-3'(SEQ ID NO:4173)
5'-ACAAAAGAUUUGUUUUUGUAGAGat-3'(SEQ ID NO:3471)
3'-AUUGUUUUCUAAACAAAAACAUCUCUA-5'(SEQ ID NO:2768)
KRAS-4166靶:5'-TAACAAAAGATTTGTTTTTGTAGAGAT-3'(SEQ ID NO:4174)
5'-CAAAAGAUUUGUUUUUGUAGAGAtt-3'(SEQ ID NO:3472)
3'-UUGUUUUCUAAACAAAAACAUCUCUAA-5'(SEQ ID NO:2769)
KRAS-4167靶:5'-AACAAAAGATTTGTTTTTGTAGAGATT-3'(SEQ ID NO:4175)
5'-AAAGAUUUGUUUUUGUAGAGAUUtt-3'(SEQ ID NO:3473)
3'-GUUUUCUAAACAAAAACAUCUCUAAAA-5'(SEQ ID NO:2770)
KRAS-4169靶:5'-CAAAAGATTTGTTTTTGTAGAGATTTT-3'(SEQ ID NO:4176)
5'-AAGAUUUGUUUUUGUAGAGAUUUta-3'(SEQ ID NO:3474)
3'-UUUUCUAAACAAAAACAUCUCUAAAAU-5'(SEQ ID NO:2771)
KRAS-4170靶:5'-AAAAGATTTGTTTTTGTAGAGATTTTA-3'(SEQ ID NO:4177)
5'-AGAUUUGUUUUUGUAGAGAUUUUaa-3'(SEQ ID NO:3475)
3'-UUUCUAAACAAAAACAUCUCUAAAAUU-5'(SEQ ID NO:2772)
KRAS-4171靶:5'-AAAGATTTGTTTTTGTAGAGATTTTAA-3'(SEQ ID NO:4178)
5'-GAUUUGUUUUUGUAGAGAUUUUAaa-3'(SEQ ID NO:3476)
3'-UUCUAAACAAAAACAUCUCUAAAAUUU-5'(SEQ ID NO:2773)
KRAS-4172靶:5'-AAGATTTGTTTTTGTAGAGATTTTAAA-3'(SEQ ID NO:4179)
5'-UUUUUGUAGAGAUUUUAAAGGGGga-3'(SEQ ID NO:3477)
3'-ACAAAAACAUCUCUAAAAUUUCCCCCU-5'(SEQ ID NO:2774)
KRAS-4178靶:5'-TGTTTTTGTAGAGATTTTAAAGGGGGA-3'(SEQ ID NO:4180)
5'-AAGGGGGAGAAUUCUAGAAAUAAat-3'(SEQ ID NO:3478)
3'-AUUUCCCCCUCUUAAGAUCUUUAUUUA-5'(SEQ ID NO:2775)
KRAS-4195靶:5'-TAAAGGGGGAGAATTCTAGAAATAAAT-3'(SEQ ID NO:4181)
5'-GGGGGAGAAUUCUAGAAAUAAAUgt-3'(SEQ ID NO:3479)
3'-UUCCCCCUCUUAAGAUCUUUAUUUACA-5'(SEQ ID NO:2776)
KRAS-4197靶:5'-AAGGGGGAGAATTCTAGAAATAAATGT-3'(SEQ ID NO:4182)
5'-GGGGAGAAUUCUAGAAAUAAAUGtt-3'(SEQ ID NO:3480)
3'-UCCCCCUCUUAAGAUCUUUAUUUACAA-5'(SEQ ID NO:2777)
KRAS-4198靶:5'-AGGGGGAGAATTCTAGAAATAAATGTT-3'(SEQ ID NO:4183)
5'-GGGAGAAUUCUAGAAAUAAAUGUta-3'(SEQ ID NO:3481)
3'-CCCCCUCUUAAGAUCUUUAUUUACAAU-5'(SEQ ID NO:2778)
KRAS-4199靶:5'-GGGGGAGAATTCTAGAAATAAATGTTA-3'(SEQ ID NO:4184)
5'-GGAGAAUUCUAGAAAUAAAUGUUac-3'(SEQ ID NO:3482)
3'-CCCCUCUUAAGAUCUUUAUUUACAAUG-5'(SEQ ID NO:2779)
KRAS-4200靶:5'-GGGGAGAATTCTAGAAATAAATGTTAC-3'(SEQ ID NO:4185)
5'-GAGAAUUCUAGAAAUAAAUGUUAcc-3'(SEQ ID NO:3483)
3'-CCCUCUUAAGAUCUUUAUUUACAAUGG-5'(SEQ ID NO:2780)
KRAS-4201靶:5'-GGGAGAATTCTAGAAATAAATGTTACC-3'(SEQ ID NO:4186)
5'-UUCUAGAAAUAAAUGUUACCUAAtt-3'(SEQ ID NO:3484)
3'-UUAAGAUCUUUAUUUACAAUGGAUUAA-5'(SEQ ID NO:2781)
KRAS-4206靶:5'-AATTCTAGAAATAAATGTTACCTAATT-3'(SEQ ID NO:4187)
5'-UCUAGAAAUAAAUGUUACCUAAUta-3'(SEQ ID NO:3485)
3'-UAAGAUCUUUAUUUACAAUGGAUUAAU-5'(SEQ ID NO:2782)
KRAS-4207靶:5'-ATTCTAGAAATAAATGTTACCTAATTA-3'(SEQ ID NO:4188)
5'-CUAGAAAUAAAUGUUACCUAAUUat-3'(SEQ ID NO:3486)
3'-AAGAUCUUUAUUUACAAUGGAUUAAUA-5'(SEQ ID NO:2783)
KRAS-4208靶:5'-TTCTAGAAATAAATGTTACCTAATTAT-3'(SEQ ID NO:4189)
5'-UAGAAAUAAAUGUUACCUAAUUAtt-3'(SEQ ID NO:3487)
3'-AGAUCUUUAUUUACAAUGGAUUAAUAA-5'(SEQ ID NO:2784)
KRAS-4209靶:5'-TCTAGAAATAAATGTTACCTAATTATT-3'(SEQ ID NO:4190)
5'-AGAAAUAAAUGUUACCUAAUUAUta-3'(SEQ ID NO:3488)
3'-GAUCUUUAUUUACAAUGGAUUAAUAAU-5'(SEQ ID NO:2785)
KRAS-4210靶:5'-CTAGAAATAAATGTTACCTAATTATTA-3'(SEQ ID NO:4191)
5'-AAAUAAAUGUUACCUAAUUAUUAca-3'(SEQ ID NO:3489)
3'-UCUUUAUUUACAAUGGAUUAAUAAUGU-5'(SEQ ID NO:2786)
KRAS-4212靶:5'-AGAAATAAATGTTACCTAATTATTACA-3'(SEQ ID NO:4192)
5'-ACCUAAUUAUUACAGCCUUAAAGac-3'(SEQ ID NO:3490)
3'-AAUGGAUUAAUAAUGUCGGAAUUUCUG-5'(SEQ ID NO:2787)
KRAS-4223靶:5'-TTACCTAATTATTACAGCCTTAAAGAC-3'(SEQ ID NO:4193)
5'-CCUAAUUAUUACAGCCUUAAAGAca-3'(SEQ ID NO:3491)
3'-AUGGAUUAAUAAUGUCGGAAUUUCUGU-5'(SEQ ID NO:2788)
KRAS-4224靶:5'-TACCTAATTATTACAGCCTTAAAGACA-3'(SEQ ID NO:4194)
5'-CCUUAAAGACAAAAAUCCUUGUUga-3'(SEQ ID NO:3492)
3'-UCGGAAUUUCUGUUUUUAGGAACAACU-5'(SEQ ID NO:2789)
KRAS-4238靶:5'-AGCCTTAAAGACAAAAATCCTTGTTGA-3'(SEQ ID NO:4195)
5'-UAAAGACAAAAAUCCUUGUUGAAgt-3'(SEQ ID NO:3493)
3'-GAAUUUCUGUUUUUAGGAACAACUUCA-5'(SEQ ID NO:2790)
KRAS-4241靶:5'-CTTAAAGACAAAAATCCTTGTTGAAGT-3'(SEQ ID NO:4196)
5'-UCCUUGUUGAAGUUUUUUUAAAAaa-3'(SEQ ID NO:3494)
3'-UUAGGAACAACUUCAAAAAAAUUUUUU-5'(SEQ ID NO:2791)
KRAS-4253靶:5'-AATCCTTGTTGAAGTTTTTTTAAAAAA-3'(SEQ ID NO:4197)
5'-CCUUGUUGAAGUUUUUUUAAAAAaa-3'(SEQ ID NO:3495)
3'-UAGGAACAACUUCAAAAAAAUUUUUUU-5'(SEQ ID NO:2792)
KRAS-4254靶:5'-ATCCTTGTTGAAGTTTTTTTAAAAAAA-3'(SEQ ID NO:4198)
5'-UUGUUGAAGUUUUUUUAAAAAAAgc-3'(SEQ ID NO:3496)
3'-GGAACAACUUCAAAAAAAUUUUUUUCG-5'(SEQ ID NO:2793)
KRAS-4256靶:5'-CCTTGTTGAAGTTTTTTTAAAAAAAGC-3'(SEQ ID NO:4199)
5'-UGUUGAAGUUUUUUUAAAAAAAGct-3'(SEQ ID NO:3497)
3'-GAACAACUUCAAAAAAAUUUUUUUCGA-5'(SEQ ID NO:2794)
KRAS-4257靶:5'-CTTGTTGAAGTTTTTTTAAAAAAAGCT-3'(SEQ ID NO:4200)
5'-GAAGUUUUUUUAAAAAAAGCUAAat-3'(SEQ ID NO:3498)
3'-AACUUCAAAAAAAUUUUUUUCGAUUUA-5'(SEQ ID NO:2795)
KRAS-4261靶:5'-TTGAAGTTTTTTTAAAAAAAGCTAAAT-3'(SEQ ID NO:4201)
5'-AAGUUUUUUUAAAAAAAGCUAAAtt-3'(SEQ ID NO:3499)
3'-ACUUCAAAAAAAUUUUUUUCGAUUUAA-5'(SEQ ID NO:2796)
KRAS-4262靶:5'-TGAAGTTTTTTTAAAAAAAGCTAAATT-3'(SEQ ID NO:4202)
5'-AGUUUUUUUAAAAAAAGCUAAAUta-3'(SEQ ID NO:3500)
3'-CUUCAAAAAAAUUUUUUUCGAUUUAAU-5'(SEQ ID NO:2797)
KRAS-4263靶:5'-GAAGTTTTTTTAAAAAAAGCTAAATTA-3'(SEQ ID NO:4203)
5'-GUUUUUUUAAAAAAAGCUAAAUUac-3'(SEQ ID NO:3501)
3'-UUCAAAAAAAUUUUUUUCGAUUUAAUG-5'(SEQ ID NO:2798)
KRAS-4264靶:5'-AAGTTTTTTTAAAAAAAGCTAAATTAC-3'(SEQ ID NO:4204)
5'-UUUUUUUAAAAAAAGCUAAAUUAca-3'(SEQ ID NO:3502)
3'-UCAAAAAAAUUUUUUUCGAUUUAAUGU-5'(SEQ ID NO:2799)
KRAS-4265靶:5'-AGTTTTTTTAAAAAAAGCTAAATTACA-3'(SEQ ID NO:4205)
5'-UUUAAAAAAAGCUAAAUUACAUAga-3'(SEQ ID NO:3503)
3'-AAAAAUUUUUUUCGAUUUAAUGUAUCU-5'(SEQ ID NO:2800)
KRAS-4269靶:5'-TTTTTAAAAAAAGCTAAATTACATAGA-3'(SEQ ID NO:4206)
5'-UAAAAAAAGCUAAAUUACAUAGAct-3'(SEQ ID NO:3504)
3'-AAAUUUUUUUCGAUUUAAUGUAUCUGA-5'(SEQ ID NO:2801)
KRAS-4271靶:5'-TTTAAAAAAAGCTAAATTACATAGACT-3'(SEQ ID NO:4207)
5'-ACUUAGGCAUUAACAUGUUUGUGga-3'(SEQ ID NO:3505)
3'-UCUGAAUCCGUAAUUGUACAAACACCU-5'(SEQ ID NO:2802)
KRAS-4293靶:5'-AGACTTAGGCATTAACATGTTTGTGGA-3'(SEQ ID NO:4208)
5'-CUUAGGCAUUAACAUGUUUGUGGaa-3'(SEQ ID NO:3506)
3'-CUGAAUCCGUAAUUGUACAAACACCUU-5'(SEQ ID NO:2803)
KRAS-4294靶:5'-GACTTAGGCATTAACATGTTTGTGGAA-3'(SEQ ID NO:4209)
5'-AGCAGACGUAUAUUGUAUCAUUUga-3'(SEQ ID NO:3507)
3'-UAUCGUCUGCAUAUAACAUAGUAAACU-5'(SEQ ID NO:2804)
KRAS-4325靶:5'-ATAGCAGACGTATATTGTATCATTTGA-3'(SEQ ID NO:4210)
5'-GACGUAUAUUGUAUCAUUUGAGUga-3'(SEQ ID NO:3508)
3'-GUCUGCAUAUAACAUAGUAAACUCACU-5'(SEQ ID NO:2805)
KRAS-4329靶:5'-CAGACGTATATTGTATCATTTGAGTGA-3'(SEQ ID NO:4211)
5'-CGUAUAUUGUAUCAUUUGAGUGAat-3'(SEQ ID NO:3509)
3'-CUGCAUAUAACAUAGUAAACUCACUUA-5'(SEQ ID NO:2806)
KRAS-4331靶:5'-GACGTATATTGTATCATTTGAGTGAAT-3'(SEQ ID NO:4212)
5'-AUAUUGUAUCAUUUGAGUGAAUGtt-3'(SEQ ID NO:3510)
3'-CAUAUAACAUAGUAAACUCACUUACAA-5'(SEQ ID NO:2807)
KRAS-4334靶:5'-GTATATTGTATCATTTGAGTGAATGTT-3'(SEQ ID NO:4213)
5'-UAUUGUAUCAUUUGAGUGAAUGUtc-3'(SEQ ID NO:3511)
3'-AUAUAACAUAGUAAACUCACUUACAAG-5'(SEQ ID NO:2808)
KRAS-4335靶:5'-TATATTGTATCATTTGAGTGAATGTTC-3'(SEQ ID NO:4214)
5'-AUUGUAUCAUUUGAGUGAAUGUUcc-3'(SEQ ID NO:3512)
3'-UAUAACAUAGUAAACUCACUUACAAGG-5'(SEQ ID NO:2809)
KRAS-4336靶:5'-ATATTGTATCATTTGAGTGAATGTTCC-3'(SEQ ID NO:4215)
5'-AUAGGAAUUUAGAACCUAACUUUta-3'(SEQ ID NO:3513)
3'-CGUAUCCUUAAAUCUUGGAUUGAAAAU-5'(SEQ ID NO:2810)
KRAS-4402靶:5'-GCATAGGAATTTAGAACCTAACTTTTA-3'(SEQ ID NO:4216)
5'-UAGGAAUUUAGAACCUAACUUUUat-3'(SEQ ID NO:3514)
3'-GUAUCCUUAAAUCUUGGAUUGAAAAUA-5'(SEQ ID NO:2811)
KRAS-4403靶:5'-CATAGGAATTTAGAACCTAACTTTTAT-3'(SEQ ID NO:4217)
5'-AAUUUAGAACCUAACUUUUAUAGgt-3'(SEQ ID NO:3515)
3'-CCUUAAAUCUUGGAUUGAAAAUAUCCA-5'(SEQ ID NO:2812)
KRAS-4407靶:5'-GGAATTTAGAACCTAACTTTTATAGGT-3'(SEQ ID NO:4218)
5'-AUUUAGAACCUAACUUUUAUAGGtt-3'(SEQ ID NO:3516)
3'-CUUAAAUCUUGGAUUGAAAAUAUCCAA-5'(SEQ ID NO:2813)
KRAS-4408靶:5'-GAATTTAGAACCTAACTTTTATAGGTT-3'(SEQ ID NO:4219)
5'-UUUAGAACCUAACUUUUAUAGGUta-3'(SEQ ID NO:3517)
3'-UUAAAUCUUGGAUUGAAAAUAUCCAAU-5'(SEQ ID NO:2814)
KRAS-4409靶:5'-AATTTAGAACCTAACTTTTATAGGTTA-3'(SEQ ID NO:4220)
5'-UUAGAACCUAACUUUUAUAGGUUat-3'(SEQ ID NO:3518)
3'-UAAAUCUUGGAUUGAAAAUAUCCAAUA-5'(SEQ ID NO:2815)
KRAS-4410靶:5'-ATTTAGAACCTAACTTTTATAGGTTAT-3'(SEQ ID NO:4221)
5'-UUUUAUAGGUUAUCAAAACUGUUgt-3'(SEQ ID NO:3519)
3'-UGAAAAUAUCCAAUAGUUUUGACAACA-5'(SEQ ID NO:2816)
KRAS-4422靶:5'-ACTTTTATAGGTTATCAAAACTGTTGT-3'(SEQ ID NO:4222)
5'-UUAUAGGUUAUCAAAACUGUUGUca-3'(SEQ ID NO:3520)
3'-AAAAUAUCCAAUAGUUUUGACAACAGU-5'(SEQ ID NO:2817)
KRAS-4424靶:5'-TTTTATAGGTTATCAAAACTGTTGTCA-3'(SEQ ID NO:4223)
5'-AAUUUUGUCCUAAUAUAUACAUAga-3'(SEQ ID NO:3521)
3'-UGUUAAAACAGGAUUAUAUAUGUAUCU-5'(SEQ ID NO:2818)
KRAS-4458靶:5'-ACAATTTTGTCCTAATATATACATAGA-3'(SEQ ID NO:4224)
5'-AUUUUGUCCUAAUAUAUACAUAGaa-3'(SEQ ID NO:3522)
3'-GUUAAAACAGGAUUAUAUAUGUAUCUU-5'(SEQ ID NO:2819)
KRAS-4459靶:5'-CAATTTTGTCCTAATATATACATAGAA-3'(SEQ ID NO:4225)
5'-UUUUGUCCUAAUAUAUACAUAGAaa-3'(SEQ ID NO:3523)
3'-UUAAAACAGGAUUAUAUAUGUAUCUUU-5'(SEQ ID NO:2820)
KRAS-4460靶:5'-AATTTTGTCCTAATATATACATAGAAA-3'(SEQ ID NO:4226)
5'-CCUAAUAUAUACAUAGAAACUUUgt-3'(SEQ ID NO:3524)
3'-CAGGAUUAUAUAUGUAUCUUUGAAACA-5'(SEQ ID NO:2821)
KRAS-4466靶:5'-GTCCTAATATATACATAGAAACTTTGT-3'(SEQ ID NO:4227)
5'-UAUAUACAUAGAAACUUUGUGGGgc-3'(SEQ ID NO:3525)
3'-UUAUAUAUGUAUCUUUGAAACACCCCG-5'(SEQ ID NO:2822)
KRAS-4471靶:5'-AATATATACATAGAAACTTTGTGGGGC-3'(SEQ ID NO:4228)
5'-CACAAGUUCAUCUCAUUUGUAUUcc-3'(SEQ ID NO:3526)
3'-ACGUGUUCAAGUAGAGUAAACAUAAGG-5'(SEQ ID NO:2823)
KRAS-4514靶:5'-TGCACAAGTTCATCTCATTTGTATTCC-3'(SEQ ID NO:4229)
5'-CUCAUUUGUAUUCCAUUGAUUUUtt-3'(SEQ ID NO:3527)
3'-UAGAGUAAACAUAAGGUAACUAAAAAA-5'(SEQ ID NO:2824)
KRAS-4525靶:5'-ATCTCATTTGTATTCCATTGATTTTTT-3'(SEQ ID NO:4230)
5'-UCAUUUGUAUUCCAUUGAUUUUUtt-3'(SEQ ID NO:3528)
3'-AGAGUAAACAUAAGGUAACUAAAAAAA-5'(SEQ ID NO:2825)
KRAS-4526靶:5'-TCTCATTTGTATTCCATTGATTTTTTT-3'(SEQ ID NO:4231)
5'-CAUUUGUAUUCCAUUGAUUUUUUtt-3'(SEQ ID NO:3529)
3'-GAGUAAACAUAAGGUAACUAAAAAAAA-5'(SEQ ID NO:2826)
KRAS-4527靶:5'-CTCATTTGTATTCCATTGATTTTTTTT-3'(SEQ ID NO:4232)
5'-AUUUGUAUUCCAUUGAUUUUUUUtt-3'(SEQ ID NO:3530)
3'-AGUAAACAUAAGGUAACUAAAAAAAAA-5'(SEQ ID NO:2827)
KRAS-4528靶:5'-TCATTTGTATTCCATTGATTTTTTTTT-3'(SEQ ID NO:4233)
5'-UUUGUAUUCCAUUGAUUUUUUUUtt-3'(SEQ ID NO:3531)
3'-GUAAACAUAAGGUAACUAAAAAAAAAA-5'(SEQ ID NO:2828)
KRAS-4529靶:5'-CATTTGTATTCCATTGATTTTTTTTTT-3'(SEQ ID NO:4234)
5'-UUGUAUUCCAUUGAUUUUUUUUUtc-3'(SEQ ID NO:3532)
3'-UAAACAUAAGGUAACUAAAAAAAAAAG-5'(SEQ ID NO:2829)
KRAS-4530靶:5'-ATTTGTATTCCATTGATTTTTTTTTTC-3'(SEQ ID NO:4235)
5'-UGUAUUCCAUUGAUUUUUUUUUUct-3'(SEQ ID NO:3533)
3'-AAACAUAAGGUAACUAAAAAAAAAAGA-5'(SEQ ID NO:2830)
KRAS-4531靶:5'-TTTGTATTCCATTGATTTTTTTTTTCT-3'(SEQ ID NO:4236)
5'-CAUUGAUUUUUUUUUUCUUCUAAac-3'(SEQ ID NO:3534)
3'-AGGUAACUAAAAAAAAAAGAAGAUUUG-5'(SEQ ID NO:2831)
KRAS-4538靶:5'-TCCATTGATTTTTTTTTTCTTCTAAAC-3'(SEQ ID NO:4237)
5'-AUUGAUUUUUUUUUUCUUCUAAAca-3'(SEQ ID NO:3535)
3'-GGUAACUAAAAAAAAAAGAAGAUUUGU-5'(SEQ ID NO:2832)
KRAS-4539靶:5'-CCATTGATTTTTTTTTTCTTCTAAACA-3'(SEQ ID NO:4238)
5'-AUUUUUUUUUUCUUCUAAACAUUtt-3'(SEQ ID NO:3536)
3'-ACUAAAAAAAAAAGAAGAUUUGUAAAA-5'(SEQ ID NO:2833)
KRAS-4543靶:5'-TGATTTTTTTTTTCTTCTAAACATTTT-3'(SEQ ID NO:4239)
5'-UUUUUUUUUUCUUCUAAACAUUUtt-3'(SEQ ID NO:3537)
3'-CUAAAAAAAAAAGAAGAUUUGUAAAAA-5'(SEQ ID NO:2834)
KRAS-4544靶:5'-GATTTTTTTTTTCTTCTAAACATTTTT-3'(SEQ ID NO:4240)
5'-UUUUUUUUUCUUCUAAACAUUUUtt-3'(SEQ ID NO:3538)
3'-UAAAAAAAAAAGAAGAUUUGUAAAAAA-5'(SEQ ID NO:2835)
KRAS-4545靶:5'-ATTTTTTTTTTCTTCTAAACATTTTTT-3'(SEQ ID NO:4241)
5'-UUUUUUUUCUUCUAAACAUUUUUtc-3'(SEQ ID NO:3539)
3'-AAAAAAAAAAGAAGAUUUGUAAAAAAG-5'(SEQ ID NO:2836)
KRAS-4546靶:5'-TTTTTTTTTTCTTCTAAACATTTTTTC-3'(SEQ ID NO:4242)
5'-UUUUUUUCUUCUAAACAUUUUUUct-3'(SEQ ID NO:3540)
3'-AAAAAAAAAGAAGAUUUGUAAAAAAGA-5'(SEQ ID NO:2837)
KRAS-4547靶:5'-TTTTTTTTTCTTCTAAACATTTTTTCT-3'(SEQ ID NO:4243)
5'-AACAUUUUUUCUUCAAACAGUAUat-3'(SEQ ID NO:3541)
3'-AUUUGUAAAAAAGAAGUUUGUCAUAUA-5'(SEQ ID NO:2838)
KRAS-4560靶:5'-TAAACATTTTTTCTTCAAACAGTATAT-3'(SEQ ID NO:4244)
5'-ACAUUUUUUCUUCAAACAGUAUAta-3'(SEQ ID NO:3542)
3'-UUUGUAAAAAAGAAGUUUGUCAUAUAU-5'(SEQ ID NO:2839)
KRAS-4561靶:5'-AAACATTTTTTCTTCAAACAGTATATA-3'(SEQ ID NO:4245)
5'-CAUUUUUUCUUCAAACAGUAUAUaa-3'(SEQ ID NO:3543)
3'-UUGUAAAAAAGAAGUUUGUCAUAUAUU-5'(SEQ ID NO:2840)
KRAS-4562靶:5'-AACATTTTTTCTTCAAACAGTATATAA-3'(SEQ ID NO:4246)
5'-AUUUUUUCUUCAAACAGUAUAUAac-3'(SEQ ID NO:3544)
3'-UGUAAAAAAGAAGUUUGUCAUAUAUUG-5'(SEQ ID NO:2841)
KRAS-4563靶:5'-ACATTTTTTCTTCAAACAGTATATAAC-3'(SEQ ID NO:4247)
5'-UUUUUUCUUCAAACAGUAUAUAAct-3'(SEQ ID NO:3545)
3'-GUAAAAAAGAAGUUUGUCAUAUAUUGA-5'(SEQ ID NO:2842)
KRAS-4564靶:5'-CATTTTTTCTTCAAACAGTATATAACT-3'(SEQ ID NO:4248)
5'-UUCAAACAGUAUAUAACUUUUUUta-3'(SEQ ID NO:3546)
3'-AGAAGUUUGUCAUAUAUUGAAAAAAAU-5'(SEQ ID NO:2843)
KRAS-4571靶:5'-TCTTCAAACAGTATATAACTTTTTTTA-3'(SEQ ID NO:4249)
5'-ACAGUAUAUAACUUUUUUUAGGGga-3'(SEQ ID NO:3547)
3'-UUUGUCAUAUAUUGAAAAAAAUCCCCU-5'(SEQ ID NO:2844)
KRAS-4576靶:5'-AAACAGTATATAACTTTTTTTAGGGGA-3'(SEQ ID NO:4250)
5'-CAGUAUAUAACUUUUUUUAGGGGat-3'(SEQ ID NO:3548)
3'-UUGUCAUAUAUUGAAAAAAAUCCCCUA-5'(SEQ ID NO:2845)
KRAS-4577靶:5'-AACAGTATATAACTTTTTTTAGGGGAT-3'(SEQ ID NO:4251)
5'-AGUAUAUAACUUUUUUUAGGGGAtt-3'(SEQ ID NO:3549)
3'-UGUCAUAUAUUGAAAAAAAUCCCCUAA-5'(SEQ ID NO:2846)
KRAS-4578靶:5'-ACAGTATATAACTTTTTTTAGGGGATT-3'(SEQ ID NO:4252)
5'-GUAUAUAACUUUUUUUAGGGGAUtt-3'(SEQ ID NO:3550)
3'-GUCAUAUAUUGAAAAAAAUCCCCUAAA-5'(SEQ ID NO:2847)
KRAS-4579靶:5'-CAGTATATAACTTTTTTTAGGGGATTT-3'(SEQ ID NO:4253)
5'-AACUUUUUUUAGGGGAUUUUUUUtt-3'(SEQ ID NO:3551)
3'-UAUUGAAAAAAAUCCCCUAAAAAAAAA-5'(SEQ ID NO:2848)
KRAS-4585靶:5'-ATAACTTTTTTTAGGGGATTTTTTTTT-3'(SEQ ID NO:4254)
5'-ACUUUUUUUAGGGGAUUUUUUUUta-3'(SEQ ID NO:3552)
3'-AUUGAAAAAAAUCCCCUAAAAAAAAAU-5'(SEQ ID NO:2849)
KRAS-4586靶:5'-TAACTTTTTTTAGGGGATTTTTTTTTA-3'(SEQ ID NO:4255)
5'-GGGAUUUUUUUUUAGACAGCAAAaa-3'(SEQ ID NO:3553)
3'-UCCCCUAAAAAAAAAUCUGUCGUUUUU-5'(SEQ ID NO:2850)
KRAS-4597靶:5'-AGGGGATTTTTTTTTAGACAGCAAAAA-3'(SEQ ID NO:4256)
5'-GGAUUUUUUUUUAGACAGCAAAAac-3'(SEQ ID NO:3554)
3'-CCCCUAAAAAAAAAUCUGUCGUUUUUG-5'(SEQ ID NO:2851)
KRAS-4598靶:5'-GGGGATTTTTTTTTAGACAGCAAAAAC-3'(SEQ ID NO:4257)
5'-GAUUUUUUUUUAGACAGCAAAAAct-3'(SEQ ID NO:3555)
3'-CCCUAAAAAAAAAUCUGUCGUUUUUGA-5'(SEQ ID NO:2852)
KRAS-4599靶:5'-GGGATTTTTTTTTAGACAGCAAAAACT-3'(SEQ ID NO:4258)
5'-UGAAGAUUUCCAUUUGUCAAAAAgt-3'(SEQ ID NO:3556)
3'-AGACUUCUAAAGGUAAACAGUUUUUCA-5'(SEQ ID NO:2853)
KRAS-4627靶:5'-TCTGAAGATTTCCATTTGTCAAAAAGT-3'(SEQ ID NO:4259)
5'-GAAGAUUUCCAUUUGUCAAAAAGta-3'(SEQ ID NO:3557)
3'-GACUUCUAAAGGUAAACAGUUUUUCAU-5'(SEQ ID NO:2854)
KRAS-4628靶:5'-CTGAAGATTTCCATTTGTCAAAAAGTA-3'(SEQ ID NO:4260)
5'-AAGAUUUCCAUUUGUCAAAAAGUaa-3'(SEQ ID NO:3558)
3'-ACUUCUAAAGGUAAACAGUUUUUCAUU-5'(SEQ ID NO:2855)
KRAS-4629靶:5'-TGAAGATTTCCATTTGTCAAAAAGTAA-3'(SEQ ID NO:4261)
5'-AGAUUUCCAUUUGUCAAAAAGUAat-3'(SEQ ID NO:3559)
3'-CUUCUAAAGGUAAACAGUUUUUCAUUA-5'(SEQ ID NO:2856)
KRAS-4630靶:5'-GAAGATTTCCATTTGTCAAAAAGTAAT-3'(SEQ ID NO:4262)
5'-UCCAUUUGUCAAAAAGUAAUGAUtt-3'(SEQ ID NO:3560)
3'-AAAGGUAAACAGUUUUUCAUUACUAAA-5'(SEQ ID NO:2857)
KRAS-4635靶:5'-TTTCCATTTGTCAAAAAGTAATGATTT-3'(SEQ ID NO:4263)
5'-CCAUUUGUCAAAAAGUAAUGAUUtc-3'(SEQ ID NO:3561)
3'-AAGGUAAACAGUUUUUCAUUACUAAAG-5'(SEQ ID NO:2858)
KRAS-4636靶:5'-TTCCATTTGTCAAAAAGTAATGATTTC-3'(SEQ ID NO:4264)
5'-CAUUUGUCAAAAAGUAAUGAUUUct-3'(SEQ ID NO:3562)
3'-AGGUAAACAGUUUUUCAUUACUAAAGA-5'(SEQ ID NO:2859)
KRAS-4637靶:5'-TCCATTTGTCAAAAAGTAATGATTTCT-3'(SEQ ID NO:4265)
5'-GUCAAAAAGUAAUGAUUUCUUGAta-3'(SEQ ID NO:3563)
3'-AACAGUUUUUCAUUACUAAAGAACUAU-5'(SEQ ID NO:2860)
KRAS-4642靶:5'-TTGTCAAAAAGTAATGATTTCTTGATA-3'(SEQ ID NO:4266)
5'-UCAAAAAGUAAUGAUUUCUUGAUaa-3'(SEQ ID NO:3564)
3'-ACAGUUUUUCAUUACUAAAGAACUAUU-5'(SEQ ID NO:2861)
KRAS-4643靶:5'-TGTCAAAAAGTAATGATTTCTTGATAA-3'(SEQ ID NO:4267)
5'-CAAAAAGUAAUGAUUUCUUGAUAat-3'(SEQ ID NO:3565)
3'-CAGUUUUUCAUUACUAAAGAACUAUUA-5'(SEQ ID NO:2862)
KRAS-4644靶:5'-GTCAAAAAGTAATGATTTCTTGATAAT-3'(SEQ ID NO:4268)
5'-AAAAAGUAAUGAUUUCUUGAUAAtt-3'(SEQ ID NO:3566)
3'-AGUUUUUCAUUACUAAAGAACUAUUAA-5'(SEQ ID NO:2863)
KRAS-4645靶:5'-TCAAAAAGTAATGATTTCTTGATAATT-3'(SEQ ID NO:4269)
5'-AAAGUAAUGAUUUCUUGAUAAUUgt-3'(SEQ ID NO:3567)
3'-UUUUUCAUUACUAAAGAACUAUUAACA-5'(SEQ ID NO:2864)
KRAS-4647靶:5'-AAAAAGTAATGATTTCTTGATAATTGT-3'(SEQ ID NO:4270)
5'-AGUAAUGAUUUCUUGAUAAUUGUgt-3'(SEQ ID NO:3568)
3'-UUUCAUUACUAAAGAACUAUUAACACA-5'(SEQ ID NO:2865)
KRAS-4649靶:5'-AAAGTAATGATTTCTTGATAATTGTGT-3'(SEQ ID NO:4271)
5'-GUAAUGAUUUCUUGAUAAUUGUGta-3'(SEQ ID NO:3569)
3'-UUCAUUACUAAAGAACUAUUAACACAU-5'(SEQ ID NO:2866)
KRAS-4650靶:5'-AAGTAATGATTTCTTGATAATTGTGTA-3'(SEQ ID NO:4272)
5'-AAUGAUUUCUUGAUAAUUGUGUAgt-3'(SEQ ID NO:3570)
3'-CAUUACUAAAGAACUAUUAACACAUCA-5'(SEQ ID NO:2867)
KRAS-4652靶:5'-GTAATGATTTCTTGATAATTGTGTAGT-3'(SEQ ID NO:4273)
5'-AUGAUUUCUUGAUAAUUGUGUAGta-3'(SEQ ID NO:3571)
3'-AUUACUAAAGAACUAUUAACACAUCAU-5'(SEQ ID NO:2868)
KRAS-4653靶:5'-TAATGATTTCTTGATAATTGTGTAGTA-3'(SEQ ID NO:4274)
5'-UUCUUGAUAAUUGUGUAGUAAUGtt-3'(SEQ ID NO:3572)
3'-UAAAGAACUAUUAACACAUCAUUACAA-5'(SEQ ID NO:2869)
KRAS-4658靶:5'-ATTTCTTGATAATTGTGTAGTAATGTT-3'(SEQ ID NO:4275)
5'-UCUUGAUAAUUGUGUAGUAAUGUtt-3'(SEQ ID NO:3573)
3'-AAAGAACUAUUAACACAUCAUUACAAA-5'(SEQ ID NO:2870)
KRAS-4659靶:5'-TTTCTTGATAATTGTGTAGTAATGTTT-3'(SEQ ID NO:4276)
5'-CUUGAUAAUUGUGUAGUAAUGUUtt-3'(SEQ ID NO:3574)
3'-AAGAACUAUUAACACAUCAUUACAAAA-5'(SEQ ID NO:2871)
KRAS-4660靶:5'-TTCTTGATAATTGTGTAGTAATGTTTT-3'(SEQ ID NO:4277)
5'-UGAUAAUUGUGUAGUAAUGUUUUtt-3'(SEQ ID NO:3575)
3'-GAACUAUUAACACAUCAUUACAAAAAA-5'(SEQ ID NO:2872)
KRAS-4662靶:5'-CTTGATAATTGTGTAGTAATGTTTTTT-3'(SEQ ID NO:4278)
5'-UAAUUGUGUAGUAAUGUUUUUUAga-3'(SEQ ID NO:3576)
3'-CUAUUAACACAUCAUUACAAAAAAUCU-5'(SEQ ID NO:2873)
KRAS-4665靶:5'-GATAATTGTGTAGTAATGTTTTTTAGA-3'(SEQ ID NO:4279)
5'-AUUGUGUAGUAAUGUUUUUUAGAac-3'(SEQ ID NO:3577)
3'-AUUAACACAUCAUUACAAAAAAUCUUG-5'(SEQ ID NO:2874)
KRAS-4667靶:5'-TAATTGTGTAGTAATGTTTTTTAGAAC-3'(SEQ ID NO:4280)
5'-UUGUGUAGUAAUGUUUUUUAGAAcc-3'(SEQ ID NO:3578)
3'-UUAACACAUCAUUACAAAAAAUCUUGG-5'(SEQ ID NO:2875)
KRAS-4668靶:5'-AATTGTGTAGTAATGTTTTTTAGAACC-3'(SEQ ID NO:4281)
5'-CCUUAAAGCUGAAUUUAUAUUUAgt-3'(SEQ ID NO:3579)
3'-AUGGAAUUUCGACUUAAAUAUAAAUCA-5'(SEQ ID NO:2876)
KRAS-4702靶:5'-TACCTTAAAGCTGAATTTATATTTAGT-3'(SEQ ID NO:4282)
5'-UUAAAGCUGAAUUUAUAUUUAGUaa-3'(SEQ ID NO:3580)
3'-GGAAUUUCGACUUAAAUAUAAAUCAUU-5'(SEQ ID NO:2877)
KRAS-4704靶:5'-CCTTAAAGCTGAATTTATATTTAGTAA-3'(SEQ ID NO:4283)
5'-AAUUUAUAUUUAGUAACUUCUGUgt-3'(SEQ ID NO:3581)
3'-ACUUAAAUAUAAAUCAUUGAAGACACA-5'(SEQ ID NO:2878)
KRAS-4713靶:5'-TGAATTTATATTTAGTAACTTCTGTGT-3'(SEQ ID NO:4284)
5'-AUUUAUAUUUAGUAACUUCUGUGtt-3'(SEQ ID NO:3582)
3'-CUUAAAUAUAAAUCAUUGAAGACACAA-5'(SEQ ID NO:2879)
KRAS-4714靶:5'-GAATTTATATTTAGTAACTTCTGTGTT-3'(SEQ ID NO:4285)
5'-UUUAUAUUUAGUAACUUCUGUGUta-3'(SEQ ID NO:3583)
3'-UUAAAUAUAAAUCAUUGAAGACACAAU-5'(SEQ ID NO:2880)
KRAS-4715靶:5'-AATTTATATTTAGTAACTTCTGTGTTA-3'(SEQ ID NO:4286)
5'-AUUUAGUAACUUCUGUGUUAAUAct-3'(SEQ ID NO:3584)
3'-UAUAAAUCAUUGAAGACACAAUUAUGA-5'(SEQ ID NO:2881)
KRAS-4720靶:5'-ATATTTAGTAACTTCTGTGTTAATACT-3'(SEQ ID NO:4287)
5'-ACUGAAUAGCUGUCAUAAAAUGAaa-3'(SEQ ID NO:3585)
3'-UUUGACUUAUCGACAGUAUUUUACUUU-5'(SEQ ID NO:2882)
KRAS-4771靶:5'-AAACTGAATAGCTGTCATAAAATGAAA-3'(SEQ ID NO:4288)
5'-CUGAAUAGCUGUCAUAAAAUGAAac-3'(SEQ ID NO:3586)
3'-UUGACUUAUCGACAGUAUUUUACUUUG-5'(SEQ ID NO:2883)
KRAS-4772靶:5'-AACTGAATAGCTGTCATAAAATGAAAC-3'(SEQ ID NO:4289)
5'-UAAAAUGAAACUUUCUUUCUAAAga-3'(SEQ ID NO:3587)
3'-GUAUUUUACUUUGAAAGAAAGAUUUCU-5'(SEQ ID NO:2884)
KRAS-4786靶:5'-CATAAAATGAAACTTTCTTTCTAAAGA-3'(SEQ ID NO:4290)
5'-AAAAUGAAACUUUCUUUCUAAAGaa-3'(SEQ ID NO:3588)
3'-UAUUUUACUUUGAAAGAAAGAUUUCUU-5'(SEQ ID NO:2885)
KRAS-4787靶:5'-ATAAAATGAAACTTTCTTTCTAAAGAA-3'(SEQ ID NO:4291)
5'-AAAUGAAACUUUCUUUCUAAAGAaa-3'(SEQ ID NO:3589)
3'-AUUUUACUUUGAAAGAAAGAUUUCUUU-5'(SEQ ID NO:2886)
KRAS-4788靶:5'-TAAAATGAAACTTTCTTTCTAAAGAAA-3'(SEQ ID NO:4292)
5'-AUGAAACUUUCUUUCUAAAGAAAga-3'(SEQ ID NO:3590)
3'-UUUACUUUGAAAGAAAGAUUUCUUUCU-5'(SEQ ID NO:2887)
KRAS-4790靶:5'-AAATGAAACTTTCTTTCTAAAGAAAGA-3'(SEQ ID NO:4293)
5'-AACUUUCUUUCUAAAGAAAGAUAct-3'(SEQ ID NO:3591)
3'-CUUUGAAAGAAAGAUUUCUUUCUAUGA-5'(SEQ ID NO:2888)
KRAS-4794靶:5'-GAAACTTTCTTTCTAAAGAAAGATACT-3'(SEQ ID NO:4294)
5'-CACAUGAGUUCUUGAAGAAUAGUca-3'(SEQ ID NO:3592)
3'-GAGUGUACUCAAGAACUUCUUAUCAGU-5'(SEQ ID NO:2889)
KRAS-4819靶:5'-CTCACATGAGTTCTTGAAGAATAGTCA-3'(SEQ ID NO:4295)
5'-UCUUGAAGAAUAGUCAUAACUAGat-3'(SEQ ID NO:3593)
3'-CAAGAACUUCUUAUCAGUAUUGAUCUA-5'(SEQ ID NO:2890)
KRAS-4828靶:5'-GTTCTTGAAGAATAGTCATAACTAGAT-3'(SEQ ID NO:4296)
5'-CUUGAAGAAUAGUCAUAACUAGAtt-3'(SEQ ID NO:3594)
3'-AAGAACUUCUUAUCAGUAUUGAUCUAA-5'(SEQ ID NO:2891)
KRAS-4829靶:5'-TTCTTGAAGAATAGTCATAACTAGATT-3'(SEQ ID NO:4297)
5'-UUGAAGAAUAGUCAUAACUAGAUta-3'(SEQ ID NO:3595)
3'-AGAACUUCUUAUCAGUAUUGAUCUAAU-5'(SEQ ID NO:2892)
KRAS-4830靶:5'-TCTTGAAGAATAGTCATAACTAGATTA-3'(SEQ ID NO:4298)
5'-AAGAAUAGUCAUAACUAGAUUAAga-3'(SEQ ID NO:3596)
3'-ACUUCUUAUCAGUAUUGAUCUAAUUCU-5'(SEQ ID NO:2893)
KRAS-4833靶:5'-TGAAGAATAGTCATAACTAGATTAAGA-3'(SEQ ID NO:4299)
5'-AGAAUAGUCAUAACUAGAUUAAGat-3'(SEQ ID NO:3597)
3'-CUUCUUAUCAGUAUUGAUCUAAUUCUA-5'(SEQ ID NO:2894)
KRAS-4834靶:5'-GAAGAATAGTCATAACTAGATTAAGAT-3'(SEQ ID NO:4300)
5'-GAAUAGUCAUAACUAGAUUAAGAtc-3'(SEQ ID NO:3598)
3'-UUCUUAUCAGUAUUGAUCUAAUUCUAG-5'(SEQ ID NO:2895)
KRAS-4835靶:5'-AAGAATAGTCATAACTAGATTAAGATC-3'(SEQ ID NO:4301)
5'-AAUAGUCAUAACUAGAUUAAGAUct-3'(SEQ ID NO:3599)
3'-UCUUAUCAGUAUUGAUCUAAUUCUAGA-5'(SEQ ID NO:2896)
KRAS-4836靶:5'-AGAATAGTCATAACTAGATTAAGATCT-3'(SEQ ID NO:4302)
5'-GUCAUAACUAGAUUAAGAUCUGUgt-3'(SEQ ID NO:3600)
3'-AUCAGUAUUGAUCUAAUUCUAGACACA-5'(SEQ ID NO:2897)
KRAS-4840靶:5'-TAGTCATAACTAGATTAAGATCTGTGT-3'(SEQ ID NO:4303)
5'-ACUAGAUUAAGAUCUGUGUUUUAgt-3'(SEQ ID NO:3601)
3'-AUUGAUCUAAUUCUAGACACAAAAUCA-5'(SEQ ID NO:2898)
KRAS-4846靶:5'-TAACTAGATTAAGATCTGTGTTTTAGT-3'(SEQ ID NO:4304)
5'-UAGAUUAAGAUCUGUGUUUUAGUtt-3'(SEQ ID NO:3602)
3'-UGAUCUAAUUCUAGACACAAAAUCAAA-5'(SEQ ID NO:2899)
KRAS-4848靶:5'-ACTAGATTAAGATCTGTGTTTTAGTTT-3'(SEQ ID NO:4305)
5'-AGAUUAAGAUCUGUGUUUUAGUUta-3'(SEQ ID NO:3603)
3'-GAUCUAAUUCUAGACACAAAAUCAAAU-5'(SEQ ID NO:2900)
KRAS-4849靶:5'-CTAGATTAAGATCTGTGTTTTAGTTTA-3'(SEQ ID NO:4306)
5'-AUUAAGAUCUGUGUUUUAGUUUAat-3'(SEQ ID NO:3604)
3'-UCUAAUUCUAGACACAAAAUCAAAUUA-5'(SEQ ID NO:2901)
KRAS-4851靶:5'-AGATTAAGATCTGTGTTTTAGTTTAAT-3'(SEQ ID NO:4307)
5'-UCUGUGUUUUAGUUUAAUAGUUUga-3'(SEQ ID NO:3605)
3'-CUAGACACAAAAUCAAAUUAUCAAACU-5'(SEQ ID NO:2902)
KRAS-4858靶:5'-GATCTGTGTTTTAGTTTAATAGTTTGA-3'(SEQ ID NO:4308)
5'-CUGUGUUUUAGUUUAAUAGUUUGaa-3'(SEQ ID NO:3606)
3'-UAGACACAAAAUCAAAUUAUCAAACUU-5'(SEQ ID NO:2903)
KRAS-4859靶:5'-ATCTGTGTTTTAGTTTAATAGTTTGAA-3'(SEQ ID NO:4309)
5'-GUGUUUUAGUUUAAUAGUUUGAAgt-3'(SEQ ID NO:3607)
3'-GACACAAAAUCAAAUUAUCAAACUUCA-5'(SEQ ID NO:2904)
KRAS-4861靶:5'-CTGTGTTTTAGTTTAATAGTTTGAAGT-3'(SEQ ID NO:4310)
5'-GUUUUAGUUUAAUAGUUUGAAGUgc-3'(SEQ ID NO:3608)
3'-CACAAAAUCAAAUUAUCAAACUUCACG-5'(SEQ ID NO:2905)
KRAS-4863靶:5'-GTGTTTTAGTTTAATAGTTTGAAGTGC-3'(SEQ ID NO:4311)
5'-UUUUAGUUUAAUAGUUUGAAGUGcc-3'(SEQ ID NO:3609)
3'-ACAAAAUCAAAUUAUCAAACUUCACGG-5'(SEQ ID NO:2906)
KRAS-4864靶:5'-TGTTTTAGTTTAATAGTTTGAAGTGCC-3'(SEQ ID NO:4312)
5'-GUUUGGGAUAAUGAUAGGUAAUUta-3'(SEQ ID NO:3610)
3'-GACAAACCCUAUUACUAUCCAUUAAAU-5'(SEQ ID NO:2907)
KRAS-4890靶:5'-CTGTTTGGGATAATGATAGGTAATTTA-3'(SEQ ID NO:4313)
5'-UUGGGAUAAUGAUAGGUAAUUUAga-3'(SEQ ID NO:3611)
3'-CAAACCCUAUUACUAUCCAUUAAAUCU-5'(SEQ ID NO:2908)
KRAS-4892靶:5'-GTTTGGGATAATGATAGGTAATTTAGA-3'(SEQ ID NO:4314)
5'-GGAUAAUGAUAGGUAAUUUAGAUga-3'(SEQ ID NO:3612)
3'-ACCCUAUUACUAUCCAUUAAAUCUACU-5'(SEQ ID NO:2909)
KRAS-4895靶:5'-TGGGATAATGATAGGTAATTTAGATGA-3'(SEQ ID NO:4315)
5'-GAUAAUGAUAGGUAAUUUAGAUGaa-3'(SEQ ID NO:3613)
3'-CCCUAUUACUAUCCAUUAAAUCUACUU-5'(SEQ ID NO:2910)
KRAS-4896靶:5'-GGGATAATGATAGGTAATTTAGATGAA-3'(SEQ ID NO:4316)
5'-AAUGAUAGGUAAUUUAGAUGAAUtt-3'(SEQ ID NO:3614)
3'-UAUUACUAUCCAUUAAAUCUACUUAAA-5'(SEQ ID NO:2911)
KRAS-4899靶:5'-ATAATGATAGGTAATTTAGATGAATTT-3'(SEQ ID NO:4317)
5'-AUGAUAGGUAAUUUAGAUGAAUUta-3'(SEQ ID NO:3615)
3'-AUUACUAUCCAUUAAAUCUACUUAAAU-5'(SEQ ID NO:2912)
KRAS-4900靶:5'-TAATGATAGGTAATTTAGATGAATTTA-3'(SEQ ID NO:4318)
5'-AGGUAAUUUAGAUGAAUUUAGGGga-3'(SEQ ID NO:3616)
3'-UAUCCAUUAAAUCUACUUAAAUCCCCU-5'(SEQ ID NO:2913)
KRAS-4905靶:5'-ATAGGTAATTTAGATGAATTTAGGGGA-3'(SEQ ID NO:4319)
5'-GUAAUUUAGAUGAAUUUAGGGGAaa-3'(SEQ ID NO:3617)
3'-UCCAUUAAAUCUACUUAAAUCCCCUUU-5'(SEQ ID NO:2914)
KRAS-4907靶:5'-AGGTAATTTAGATGAATTTAGGGGAAA-3'(SEQ ID NO:4320)
5'-AGAUGAAUUUAGGGGAAAAAAAAgt-3'(SEQ ID NO:3618)
3'-AAUCUACUUAAAUCCCCUUUUUUUUCA-5'(SEQ ID NO:2915)
KRAS-4914靶:5'-TTAGATGAATTTAGGGGAAAAAAAAGT-3'(SEQ ID NO:4321)
5'-GAUGAAUUUAGGGGAAAAAAAAGtt-3'(SEQ ID NO:3619)
3'-AUCUACUUAAAUCCCCUUUUUUUUCAA-5'(SEQ ID NO:2916)
KRAS-4915靶:5'-TAGATGAATTTAGGGGAAAAAAAAGTT-3'(SEQ ID NO:4322)
5'-GGGAAAAAAAAGUUAUCUGCAGAta-3'(SEQ ID NO:3620)
3'-UCCCCUUUUUUUUCAAUAGACGUCUAU-5'(SEQ ID NO:2917)
KRAS-4926靶:5'-AGGGGAAAAAAAAGTTATCTGCAGATA-3'(SEQ ID NO:4323)
5'-GGAAAAAAAAGUUAUCUGCAGAUat-3'(SEQ ID NO:3621)
3'-CCCCUUUUUUUUCAAUAGACGUCUAUA-5'(SEQ ID NO:2918)
KRAS-4927靶:5'-GGGGAAAAAAAAGTTATCTGCAGATAT-3'(SEQ ID NO:4324)
5'-AAAAAGUUAUCUGCAGAUAUGUUga-3'(SEQ ID NO:3622)
3'-UUUUUUUCAAUAGACGUCUAUACAACU-5'(SEQ ID NO:2919)
KRAS-4932靶:5'-AAAAAAAGTTATCTGCAGATATGTTGA-3'(SEQ ID NO:4325)
5'-GUCUUGUGUUUUCAUGUUGAAAAta-3'(SEQ ID NO:3623)
3'-GACAGAACACAAAAGUACAACUUUUAU-5'(SEQ ID NO:2920)
KRAS-5033靶:5'-CTGTCTTGTGTTTTCATGTTGAAAATA-3'(SEQ ID NO:4326)
5'-UCUUGUGUUUUCAUGUUGAAAAUac-3'(SEQ ID NO:3624)
3'-ACAGAACACAAAAGUACAACUUUUAUG-5'(SEQ ID NO:2921)
KRAS-5034靶:5'-TGTCTTGTGTTTTCATGTTGAAAATAC-3'(SEQ ID NO:4327)
5'-CUUGUGUUUUCAUGUUGAAAAUAct-3'(SEQ ID NO:3625)
3'-CAGAACACAAAAGUACAACUUUUAUGA-5'(SEQ ID NO:2922)
KRAS-5035靶:5'-GTCTTGTGTTTTCATGTTGAAAATACT-3'(SEQ ID NO:4328)
5'-CAUGUUGAAAAUACUUUUGCAUUtt-3'(SEQ ID NO:3626)
3'-AAGUACAACUUUUAUGAAAACGUAAAA-5'(SEQ ID NO:2923)
KRAS-5045靶:5'-TTCATGTTGAAAATACTTTTGCATTTT-3'(SEQ ID NO:4329)
5'-AUGUUGAAAAUACUUUUGCAUUUtt-3'(SEQ ID NO:3627)
3'-AGUACAACUUUUAUGAAAACGUAAAAA-5'(SEQ ID NO:2924)
KRAS-5046靶:5'-TCATGTTGAAAATACTTTTGCATTTTT-3'(SEQ ID NO:4330)
5'-UGUUGAAAAUACUUUUGCAUUUUtc-3'(SEQ ID NO:3628)
3'-GUACAACUUUUAUGAAAACGUAAAAAG-5'(SEQ ID NO:2925)
KRAS-5047靶:5'-CATGTTGAAAATACTTTTGCATTTTTC-3'(SEQ ID NO:4331)
5'-GUUGAAAAUACUUUUGCAUUUUUcc-3'(SEQ ID NO:3629)
3'-UACAACUUUUAUGAAAACGUAAAAAGG-5'(SEQ ID NO:2926)
KRAS-5048靶:5'-ATGTTGAAAATACTTTTGCATTTTTCC-3'(SEQ ID NO:4332)
5'-CUUUUGCAUUUUUCCUUUGAGUGcc-3'(SEQ ID NO:3630)
3'-AUGAAAACGUAAAAAGGAAACUCACGG-5'(SEQ ID NO:2927)
KRAS-5058靶:5'-TACTTTTGCATTTTTCCTTTGAGTGCC-3'(SEQ ID NO:4333)
5'-UGAGUGCCAAUUUCUUACUAGUAct-3'(SEQ ID NO:3631)
3'-AAACUCACGGUUAAAGAAUGAUCAUGA-5'(SEQ ID NO:2928)
KRAS-5075靶:5'-TTTGAGTGCCAATTTCTTACTAGTACT-3'(SEQ ID NO:4334)
5'-GCCAAUUUCUUACUAGUACUAUUtc-3'(SEQ ID NO:3632)
3'-CACGGUUAAAGAAUGAUCAUGAUAAAG-5'(SEQ ID NO:2929)
KRAS-5080靶:5'-GTGCCAATTTCTTACTAGTACTATTTC-3'(SEQ ID NO:4335)
5'-CCAAUUUCUUACUAGUACUAUUUct-3'(SEQ ID NO:3633)
3'-ACGGUUAAAGAAUGAUCAUGAUAAAGA-5'(SEQ ID NO:2930)
KRAS-5081靶:5'-TGCCAATTTCTTACTAGTACTATTTCT-3'(SEQ ID NO:4336)
5'-UACUAGUACUAUUUCUUAAUGUAac-3'(SEQ ID NO:3634)
3'-GAAUGAUCAUGAUAAAGAAUUACAUUG-5'(SEQ ID NO:2931)
KRAS-5090靶:5'-CTTACTAGTACTATTTCTTAATGTAAC-3'(SEQ ID NO:4337)
5'-ACUAGUACUAUUUCUUAAUGUAAca-3'(SEQ ID NO:3635)
3'-AAUGAUCAUGAUAAAGAAUUACAUUGU-5'(SEQ ID NO:2932)
KRAS-5091靶:5'-TTACTAGTACTATTTCTTAATGTAACA-3'(SEQ ID NO:4338)
5'-UACUAUUUCUUAAUGUAACAUGUtt-3'(SEQ ID NO:3636)
3'-UCAUGAUAAAGAAUUACAUUGUACAAA-5'(SEQ ID NO:2933)
KRAS-5096靶:5'-AGTACTATTTCTTAATGTAACATGTTT-3'(SEQ ID NO:4339)
5'-ACUAUUUCUUAAUGUAACAUGUUta-3'(SEQ ID NO:3637)
3'-CAUGAUAAAGAAUUACAUUGUACAAAU-5'(SEQ ID NO:2934)
KRAS-5097靶:5'-GTACTATTTCTTAATGTAACATGTTTA-3'(SEQ ID NO:4340)
5'-CUAUUUCUUAAUGUAACAUGUUUac-3'(SEQ ID NO:3638)
3'-AUGAUAAAGAAUUACAUUGUACAAAUG-5'(SEQ ID NO:2935)
KRAS-5098靶:5'-TACTATTTCTTAATGTAACATGTTTAC-3'(SEQ ID NO:4341)
5'-UUAAUGUAACAUGUUUACCUGGAat-3'(SEQ ID NO:3639)
3'-AGAAUUACAUUGUACAAAUGGACCUUA-5'(SEQ ID NO:2936)
KRAS-5105靶:5'-TCTTAATGTAACATGTTTACCTGGAAT-3'(SEQ ID NO:4342)
5'-CCUGGAAUGUAUUUUAACUAUUUtt-3'(SEQ ID NO:3640)
3'-AUGGACCUUACAUAAAAUUGAUAAAAA-5'(SEQ ID NO:2937)
KRAS-5122靶:5'-TACCTGGAATGTATTTTAACTATTTTT-3'(SEQ ID NO:4343)
5'-UGGAAUGUAUUUUAACUAUUUUUgt-3'(SEQ ID NO:3641)
3'-GGACCUUACAUAAAAUUGAUAAAAACA-5'(SEQ ID NO:2938)
KRAS-5124靶:5'-CCTGGAATGTATTTTAACTATTTTTGT-3'(SEQ ID NO:4344)
5'-GGAAUGUAUUUUAACUAUUUUUGta-3'(SEQ ID NO:3642)
3'-GACCUUACAUAAAAUUGAUAAAAACAU-5'(SEQ ID NO:2939)
KRAS-5125靶:5'-CTGGAATGTATTTTAACTATTTTTGTA-3'(SEQ ID NO:4345)
5'-GAAUGUAUUUUAACUAUUUUUGUat-3'(SEQ ID NO:3643)
3'-ACCUUACAUAAAAUUGAUAAAAACAUA-5'(SEQ ID NO:2940)
KRAS-5126靶:5'-TGGAATGTATTTTAACTATTTTTGTAT-3'(SEQ ID NO:4346)
5'-AAUGUAUUUUAACUAUUUUUGUAta-3'(SEQ ID NO:3644)
3'-CCUUACAUAAAAUUGAUAAAAACAUAU-5'(SEQ ID NO:2941)
KRAS-5127靶:5'-GGAATGTATTTTAACTATTTTTGTATA-3'(SEQ ID NO:4347)
5'-UGUAUUUUAACUAUUUUUGUAUAgt-3'(SEQ ID NO:3645)
3'-UUACAUAAAAUUGAUAAAAACAUAUCA-5'(SEQ ID NO:2942)
KRAS-5129靶:5'-AATGTATTTTAACTATTTTTGTATAGT-3'(SEQ ID NO:4348)
5'-UAUUUUAACUAUUUUUGUAUAGUgt-3'(SEQ ID NO:3646)
3'-ACAUAAAAUUGAUAAAAACAUAUCACA-5'(SEQ ID NO:2943)
KRAS-5131靶:5'-TGTATTTTAACTATTTTTGTATAGTGT-3'(SEQ ID NO:4349)
5'-AUUUUAACUAUUUUUGUAUAGUGta-3'(SEQ ID NO:3647)
3'-CAUAAAAUUGAUAAAAACAUAUCACAU-5'(SEQ ID NO:2944)
KRAS-5132靶:5'-GTATTTTAACTATTTTTGTATAGTGTA-3'(SEQ ID NO:4350)
5'-UUUUAACUAUUUUUGUAUAGUGUaa-3'(SEQ ID NO:3648)
3'-AUAAAAUUGAUAAAAACAUAUCACAUU-5'(SEQ ID NO:2945)
KRAS-5133靶:5'-TATTTTAACTATTTTTGTATAGTGTAA-3'(SEQ ID NO:4351)
5'-UAUUUUUGUAUAGUGUAAACUGAaa-3'(SEQ ID NO:3649)
3'-UGAUAAAAACAUAUCACAUUUGACUUU-5'(SEQ ID NO:2946)
KRAS-5140靶:5'-ACTATTTTTGTATAGTGTAAACTGAAA-3'(SEQ ID NO:4352)
5'-AUUUUUGUAUAGUGUAAACUGAAac-3'(SEQ ID NO:3650)
3'-GAUAAAAACAUAUCACAUUUGACUUUG-5'(SEQ ID NO:2947)
KRAS-5141靶:5'-CTATTTTTGTATAGTGTAAACTGAAAC-3'(SEQ ID NO:4353)
5'-UUUUUGUAUAGUGUAAACUGAAAca-3'(SEQ ID NO:3651)
3'-AUAAAAACAUAUCACAUUUGACUUUGU-5'(SEQ ID NO:2948)
KRAS-5142靶:5'-TATTTTTGTATAGTGTAAACTGAAACA-3'(SEQ ID NO:4354)
5'-AACUGAAACAUGCACAUUUUGUAca-3'(SEQ ID NO:3652)
3'-AUUUGACUUUGUACGUGUAAAACAUGU-5'(SEQ ID NO:2949)
KRAS-5157靶:5'-TAAACTGAAACATGCACATTTTGTACA-3'(SEQ ID NO:4355)
5'-AACAUGCACAUUUUGUACAUUGUgc-3'(SEQ ID NO:3653)
3'-CUUUGUACGUGUAAAACAUGUAACACG-5'(SEQ ID NO:2950)
KRAS-5163靶:5'-GAAACATGCACATTTTGTACATTGTGC-3'(SEQ ID NO:4356)
5'-UCCAGUUGUUUUCCAUCAUUUGGtt-3'(SEQ ID NO:3654)
3'-CUAGGUCAACAAAAGGUAGUAAACCAA-5'(SEQ ID NO:2951)
KRAS-5216靶:5'-GATCCAGTTGTTTTCCATCATTTGGTT-3'(SEQ ID NO:4357)
5'-CAGUUGUUUUCCAUCAUUUGGUUgc-3'(SEQ ID NO:3655)
3'-AGGUCAACAAAAGGUAGUAAACCAACG-5'(SEQ ID NO:2952)
KRAS-5218靶:5'-TCCAGTTGTTTTCCATCATTTGGTTGC-3'(SEQ ID NO:4358)
5'-AUGUUGGUCAUAUCAAACAUUAAaa-3'(SEQ ID NO:3656)
3'-CUUACAACCAGUAUAGUUUGUAAUUUU-5'(SEQ ID NO:2953)
KRAS-5255靶:5'-GAATGTTGGTCATATCAAACATTAAAA-3'(SEQ ID NO:4359)
5'-UGUUGGUCAUAUCAAACAUUAAAaa-3'(SEQ ID NO:3657)
3'-UUACAACCAGUAUAGUUUGUAAUUUUU-5'(SEQ ID NO:2954)
KRAS-5256靶:5'-AATGTTGGTCATATCAAACATTAAAAA-3'(SEQ ID NO:4360)
5'-GUUGGUCAUAUCAAACAUUAAAAat-3'(SEQ ID NO:3658)
3'-UACAACCAGUAUAGUUUGUAAUUUUUA-5'(SEQ ID NO:2955)
KRAS-5257靶:5'-ATGTTGGTCATATCAAACATTAAAAAT-3'(SEQ ID NO:4361)
5'-GUCAUAUCAAACAUUAAAAAUGAcc-3'(SEQ ID NO:3659)
3'-ACCAGUAUAGUUUGUAAUUUUUACUGG-5'(SEQ ID NO:2956)
KRAS-5261靶:5'-TGGTCATATCAAACATTAAAAATGACC-3'(SEQ ID NO:4362)
5'-AAAAUGACCACUCUUUUAAUUGAaa-3'(SEQ ID NO:3660)
3'-AUUUUUACUGGUGAGAAAAUUAACUUU-5'(SEQ ID NO:2957)
KRAS-5277靶:5'-TAAAAATGACCACTCTTTTAATTGAAA-3'(SEQ ID NO:4363)
5'-AAAUGACCACUCUUUUAAUUGAAat-3'(SEQ ID NO:3661)
3'-UUUUUACUGGUGAGAAAAUUAACUUUA-5'(SEQ ID NO:2958)
KRAS-5278靶:5'-AAAAATGACCACTCTTTTAATTGAAAT-3'(SEQ ID NO:4364)
5'-CUCUUUUAAUUGAAAUUAACUUUta-3'(SEQ ID NO:3662)
3'-GUGAGAAAAUUAACUUUAAUUGAAAAU-5'(SEQ ID NO:2959)
KRAS-5287靶:5'-CACTCTTTTAATTGAAATTAACTTTTA-3'(SEQ ID NO:4365)
5'-UCUUUUAAUUGAAAUUAACUUUUaa-3'(SEQ ID NO:3663)
3'-UGAGAAAAUUAACUUUAAUUGAAAAUU-5'(SEQ ID NO:2960)
KRAS-5288靶:5'-ACTCTTTTAATTGAAATTAACTTTTAA-3'(SEQ ID NO:4366)
5'-UUUUAAUUGAAAUUAACUUUUAAat-3'(SEQ ID NO:3664)
3'-AGAAAAUUAACUUUAAUUGAAAAUUUA-5'(SEQ ID NO:2961)
KRAS-5290靶:5'-TCTTTTAATTGAAATTAACTTTTAAAT-3'(SEQ ID NO:4367)
5'-UUAAUUGAAAUUAACUUUUAAAUgt-3'(SEQ ID NO:3665)
3'-AAAAUUAACUUUAAUUGAAAAUUUACA-5'(SEQ ID NO:2962)
KRAS-5292靶:5'-TTTTAATTGAAATTAACTTTTAAATGT-3'(SEQ ID NO:4368)
5'-UAAUUGAAAUUAACUUUUAAAUGtt-3'(SEQ ID NO:3666)
3'-AAAUUAACUUUAAUUGAAAAUUUACAA-5'(SEQ ID NO:2963)
KRAS-5293靶:5'-TTTAATTGAAATTAACTTTTAAATGTT-3'(SEQ ID NO:4369)
5'-AAUUGAAAUUAACUUUUAAAUGUtt-3'(SEQ ID NO:3667)
3'-AAUUAACUUUAAUUGAAAAUUUACAAA-5'(SEQ ID NO:2964)
KRAS-5294靶:5'-TTAATTGAAATTAACTTTTAAATGTTT-3'(SEQ ID NO:4370)
5'-AUUGAAAUUAACUUUUAAAUGUUta-3'(SEQ ID NO:3668)
3'-AUUAACUUUAAUUGAAAAUUUACAAAU-5'(SEQ ID NO:2965)
KRAS-5295靶:5'-TAATTGAAATTAACTTTTAAATGTTTA-3'(SEQ ID NO:4371)
5'-UUGAAAUUAACUUUUAAAUGUUUat-3'(SEQ ID NO:3669)
3'-UUAACUUUAAUUGAAAAUUUACAAAUA-5'(SEQ ID NO:2966)
KRAS-5296靶:5'-AATTGAAATTAACTTTTAAATGTTTAT-3'(SEQ ID NO:4372)
5'-UGAAAUUAACUUUUAAAUGUUUAta-3'(SEQ ID NO:3670)
3'-UAACUUUAAUUGAAAAUUUACAAAUAU-5'(SEQ ID NO:2967)
KRAS-5297靶:5'-ATTGAAATTAACTTTTAAATGTTTATA-3'(SEQ ID NO:4373)
5'-AAUUAACUUUUAAAUGUUUAUAGga-3'(SEQ ID NO:3671)
3'-CUUUAAUUGAAAAUUUACAAAUAUCCU-5'(SEQ ID NO:2968)
KRAS-5300靶:5'-GAAATTAACTTTTAAATGTTTATAGGA-3'(SEQ ID NO:4374)
5'-AACUUUUAAAUGUUUAUAGGAGUat-3'(SEQ ID NO:3672)
3'-AAUUGAAAAUUUACAAAUAUCCUCAUA-5'(SEQ ID NO:2969)
KRAS-5304靶:5'-TTAACTTTTAAATGTTTATAGGAGTAT-3'(SEQ ID NO:4375)
5'-UUUAAAUGUUUAUAGGAGUAUGUgc-3'(SEQ ID NO:3673)
3'-GAAAAUUUACAAAUAUCCUCAUACACG-5'(SEQ ID NO:2970)
KRAS-5308靶:5'-CTTTTAAATGTTTATAGGAGTATGTGC-3'(SEQ ID NO:4376)
5'-UUAAAUGUUUAUAGGAGUAUGUGct-3'(SEQ ID NO:3674)
3'-AAAAUUUACAAAUAUCCUCAUACACGA-5'(SEQ ID NO:2971)
KRAS-5309靶:5'-TTTTAAATGTTTATAGGAGTATGTGCT-3'(SEQ ID NO:4377)
5'-GCUGUGAAGUGAUCUAAAAUUUGta-3'(SEQ ID NO:3675)
3'-CACGACACUUCACUAGAUUUUAAACAU-5'(SEQ ID NO:2972)
KRAS-5331靶:5'-GTGCTGTGAAGTGATCTAAAATTTGTA-3'(SEQ ID NO:4378)
5'-UGUGAAGUGAUCUAAAAUUUGUAat-3'(SEQ ID NO:3676)
3'-CGACACUUCACUAGAUUUUAAACAUUA-5'(SEQ ID NO:2973)
KRAS-5333靶:5'-GCTGTGAAGTGATCTAAAATTTGTAAT-3'(SEQ ID NO:4379)
5'-GUGAAGUGAUCUAAAAUUUGUAAta-3'(SEQ ID NO:3677)
3'-GACACUUCACUAGAUUUUAAACAUUAU-5'(SEQ ID NO:2974)
KRAS-5334靶:5'-CTGTGAAGTGATCTAAAATTTGTAATA-3'(SEQ ID NO:4380)
5'-UGAAGUGAUCUAAAAUUUGUAAUat-3'(SEQ ID NO:3678)
3'-ACACUUCACUAGAUUUUAAACAUUAUA-5'(SEQ ID NO:2975)
KRAS-5335靶:5'-TGTGAAGTGATCTAAAATTTGTAATAT-3'(SEQ ID NO:4381)
5'-GAAGUGAUCUAAAAUUUGUAAUAtt-3'(SEQ ID NO:3679)
3'-CACUUCACUAGAUUUUAAACAUUAUAA-5'(SEQ ID NO:2976)
KRAS-5336靶:5'-GTGAAGTGATCTAAAATTTGTAATATT-3'(SEQ ID NO:4382)
5'-AAGUGAUCUAAAAUUUGUAAUAUtt-3'(SEQ ID NO:3680)
3'-ACUUCACUAGAUUUUAAACAUUAUAAA-5'(SEQ ID NO:2977)
KRAS-5337靶:5'-TGAAGTGATCTAAAATTTGTAATATTT-3'(SEQ ID NO:4383)
5'-AGUGAUCUAAAAUUUGUAAUAUUtt-3'(SEQ ID NO:3681)
3'-CUUCACUAGAUUUUAAACAUUAUAAAA-5'(SEQ ID NO:2978)
KRAS-5338靶:5'-GAAGTGATCTAAAATTTGTAATATTTT-3'(SEQ ID NO:4384)
5'-AUCUAAAAUUUGUAAUAUUUUUGtc-3'(SEQ ID NO:3682)
3'-ACUAGAUUUUAAACAUUAUAAAAACAG-5'(SEQ ID NO:2979)
KRAS-5342靶:5'-TGATCTAAAATTTGTAATATTTTTGTC-3'(SEQ ID NO:4385)
5'-UCUAAAAUUUGUAAUAUUUUUGUca-3'(SEQ ID NO:3683)
3'-CUAGAUUUUAAACAUUAUAAAAACAGU-5'(SEQ ID NO:2980)
KRAS-5343靶:5'-GATCTAAAATTTGTAATATTTTTGTCA-3'(SEQ ID NO:4386)
5'-AAAUUUGUAAUAUUUUUGUCAUGaa-3'(SEQ ID NO:3684)
3'-AUUUUAAACAUUAUAAAAACAGUACUU-5'(SEQ ID NO:2981)
KRAS-5347靶:5'-TAAAATTTGTAATATTTTTGTCATGAA-3'(SEQ ID NO:4387)
5'-AAUUUGUAAUAUUUUUGUCAUGAac-3'(SEQ ID NO:3685)
3'-UUUUAAACAUUAUAAAAACAGUACUUG-5'(SEQ ID NO:2982)
KRAS-5348靶:5'-AAAATTTGTAATATTTTTGTCATGAAC-3'(SEQ ID NO:4388)
5'-AUUUGUAAUAUUUUUGUCAUGAAct-3'(SEQ ID NO:3686)
3'-UUUAAACAUUAUAAAAACAGUACUUGA-5'(SEQ ID NO:2983)
KRAS-5349靶:5'-AAATTTGTAATATTTTTGTCATGAACT-3'(SEQ ID NO:4389)
5'-GUAAUAUUUUUGUCAUGAACUGUac-3'(SEQ ID NO:3687)
3'-AACAUUAUAAAAACAGUACUUGACAUG-5'(SEQ ID NO:2984)
KRAS-5353靶:5'-TTGTAATATTTTTGTCATGAACTGTAC-3'(SEQ ID NO:4390)
5'-UAAUAUUUUUGUCAUGAACUGUAct-3'(SEQ ID NO:3688)
3'-ACAUUAUAAAAACAGUACUUGACAUGA-5'(SEQ ID NO:2985)
KRAS-5354靶:5'-TGTAATATTTTTGTCATGAACTGTACT-3'(SEQ ID NO:4391)
5'-AACUGUACUACUCCUAAUUAUUGta-3'(SEQ ID NO:3689)
3'-ACUUGACAUGAUGAGGAUUAAUAACAU-5'(SEQ ID NO:2986)
KRAS-5370靶:5'-TGAACTGTACTACTCCTAATTATTGTA-3'(SEQ ID NO:4392)
5'-ACUGUACUACUCCUAAUUAUUGUaa-3'(SEQ ID NO:3690)
3'-CUUGACAUGAUGAGGAUUAAUAACAUU-5'(SEQ ID NO:2987)
KRAS-5371靶:5'-GAACTGTACTACTCCTAATTATTGTAA-3'(SEQ ID NO:4393)
5'-UCCUAAUUAUUGUAAUGUAAUAAaa-3'(SEQ ID NO:3691)
3'-UGAGGAUUAAUAACAUUACAUUAUUUU-5'(SEQ ID NO:2988)
KRAS-5381靶:5'-ACTCCTAATTATTGTAATGTAATAAAA-3'(SEQ ID NO:4394)
5'-CCUAAUUAUUGUAAUGUAAUAAAaa-3'(SEQ ID NO:3692)
3'-GAGGAUUAAUAACAUUACAUUAUUUUU-5'(SEQ ID NO:2989)
KRAS-5382靶:5'-CTCCTAATTATTGTAATGTAATAAAAA-3'(SEQ ID NO:4395)
5'-UAAUUAUUGUAAUGUAAUAAAAAta-3'(SEQ ID NO:3693)
3'-GGAUUAAUAACAUUACAUUAUUUUUAU-5'(SEQ ID NO:2990)
KRAS-5384靶:5'-CCTAATTATTGTAATGTAATAAAAATA-3'(SEQ ID NO:4396)
5'-AUUAUUGUAAUGUAAUAAAAAUAgt-3'(SEQ ID NO:3694)
3'-AUUAAUAACAUUACAUUAUUUUUAUCA-5'(SEQ ID NO:2991)
KRAS-5386靶:5'-TAATTATTGTAATGTAATAAAAATAGT-3'(SEQ ID NO:4397)
5'-UUAUUGUAAUGUAAUAAAAAUAGtt-3'(SEQ ID NO:3695)
3'-UUAAUAACAUUACAUUAUUUUUAUCAA-5'(SEQ ID NO:2992)
KRAS-5387靶:5'-AATTATTGTAATGTAATAAAAATAGTT-3'(SEQ ID NO:4398)
5'-AUUGUAAUGUAAUAAAAAUAGUUac-3'(SEQ ID NO:3696)
3'-AAUAACAUUACAUUAUUUUUAUCAAUG-5'(SEQ ID NO:2993)
KRAS-5389靶:5'-TTATTGTAATGTAATAAAAATAGTTAC-3'(SEQ ID NO:4399)
5'-UUGUAAUGUAAUAAAAAUAGUUAca-3'(SEQ ID NO:3697)
3'-AUAACAUUACAUUAUUUUUAUCAAUGU-5'(SEQ ID NO:2994)
KRAS-5390靶:5'-TATTGTAATGTAATAAAAATAGTTACA-3'(SEQ ID NO:4400)
5'-AAUGUAAUAAAAAUAGUUACAGUga-3'(SEQ ID NO:3698)
3'-CAUUACAUUAUUUUUAUCAAUGUCACU-5'(SEQ ID NO:2995)
KRAS-5394靶:5'-GTAATGTAATAAAAATAGTTACAGTGA-3'(SEQ ID NO:4401)
5'-AUGUAAUAAAAAUAGUUACAGUGac-3'(SEQ ID NO:3699)
3'-AUUACAUUAUUUUUAUCAAUGUCACUG-5'(SEQ ID NO:2996)
KRAS-5395靶:5'-TAATGTAATAAAAATAGTTACAGTGAC-3'(SEQ ID NO:4402)
5'-UGUAAUAAAAAUAGUUACAGUGAca-3'(SEQ ID NO:3700)
3'-UUACAUUAUUUUUAUCAAUGUCACUGU-5'(SEQ ID NO:2997)
KRAS-5396靶:5'-AATGTAATAAAAATAGTTACAGTGACA-3'(SEQ ID NO:4403)
5'-AAAUAGUUACAGUGACAAAAAAAaa-3'(SEQ ID NO:3701)
3'-UUUUUAUCAAUGUCACUGUUUUUUUUU-5'(SEQ ID NO:2998)
KRAS-5404靶:5'-AAAAATAGTTACAGTGACAAAAAAAAA-3'(SEQ ID NO:4404)
5'-AAUAGUUACAGUGACAAAAAAAAaa-3'(SEQ ID NO:3702)
3'-UUUUAUCAAUGUCACUGUUUUUUUUUU-5'(SEQ ID NO:2999)
KRAS-5405靶:5'-AAAATAGTTACAGTGACAAAAAAAAAA-3'(SEQ ID NO:4405)
5'-UAGUUACAGUGACAAAAAAAAAAaa-3'(SEQ ID NO:3703)
3'-UUAUCAAUGUCACUGUUUUUUUUUUUU-5'(SEQ ID NO:3000)
KRAS-5407靶:5'-AATAGTTACAGTGACAAAAAAAAAAAA-3'(SEQ ID NO:4406)
表6:抗KRAS不对称DsiRNA,未修饰序列
5’-GUUGGAGCUGGUGGCGUAGGCAAGA-3’(SEQ ID NO:5144)
3'-AUCAACCUCGACCACCGCAUCCGUUCU-5'(SEQ ID NO:11)
KRAS-204靶:5'-TAGTTGGAGCTGGTGGCGTAGGCAAGA-3’(SEQ ID NO:141)
5’-GUUGGAGCUGUUGGCGUAGGCAAGA-3’(SEQ ID NO:5145)
3'-AUCAACCUCGACAACCGCAUCCGUUCU-5'(SEQ ID NO:135)
KRAS-204*靶:5'-TAGTTGGAGCTGTTGGCGTAGGCAAGA-3’(SEQ ID NO:142)
5’-UAUUCUCGACACAGCAGGUCAAGAG-3’(SEQ ID NO:5146)
3'-CUAUAAGAGCUGUGUCGUCCAGUUCUC-5'(SEQ ID NO:12)
KRAS-341靶:5'-GATATTCTCGACACAGCAGGTCAAGAG-3’(SEQ ID NO:143)
5’-UAUUCUCGACACAGCAGGUCAUGAG-3’(SEQ ID NO:5147)
3'-CUAUAAGAGCUGUGUCGUCCAGUACUC-5'(SEQ ID NO:136)
KRAS-341*靶:5'-GATATTCTCGACACAGCAGGTCATGAG-3’(SEQ ID NO:144)
5’-UUCUCGACACAGCAGGUCAAGAGGA-3’(SEQ ID NO:5148)
3'-AUAAGAGCUGUGUCGUCCAGUUCUCCU-5'(SEQ ID NO:13)
KRAS-343靶:5'-TATTCTCGACACAGCAGGTCAAGAGGA-3’(SEQ ID NO:145)
5’-UUCUCGACACAGCAGGUCAUGAGGA-3’(SEQ ID NO:5149)
3'-AUAAGAGCUGUGUCGUCCAGUACUCCU-5'(SEQ ID NO:137)
KRAS-343*靶:5'-TATTCTCGACACAGCAGGTCATGAGGA-3’(SEQ ID NO:146)
5’-CAGGUCAAGAGGAGUACAGUGCAAU-3’(SEQ ID NO:5150)
3'-UCGUCCAGUUCUCCUCAUGUCACGUUA-5'(SEQ ID NO:14)
KRAS-355靶:5'-AGCAGGTCAAGAGGAGTACAGTGCAAT-3’(SEQ ID NO:147)
5’-CAGGUCAUGAGGAGUACAGUGCAAU-3’(SEQ ID NO:5151)
3'-UCGUCCAGUACUCCUCAUGUCACGUUA-5'(SEQ ID NO:138)
KRAS-355*靶:5'-AGCAGGTCATGAGGAGTACAGTGCAAT-3’(SEQ ID NO:148)
5’-AAGAGGAGUACAGUGCAAUGAGGGA-3’(SEQ ID NO:5152)
3'-AGUUCUCCUCAUGUCACGUUACUCCCU-5'(SEQ ID NO:15)
KRAS-361靶:5'-TCAAGAGGAGTACAGTGCAATGAGGGA-3’(SEQ ID NO:149)
5’-AUGAGGAGUACAGUGCAAUGAGGGA-3’(SEQ ID NO:5153)
3'-AGUACUCCUCAUGUCACGUUACUCCCU-5'(SEQ ID NO:139)
KRAS-361*靶:5'-TCATGAGGAGTACAGTGCAATGAGGGA-3’(SEQ ID NO:150)
5’-CAGUGCAAUGAGGGACCAGUACAUG-3’(SEQ ID NO:5154)
3'-AUGUCACGUUACUCCCUGGUCAUGUAC-5'(SEQ ID NO:16)
KRAS-371靶:5'-TACAGTGCAATGAGGGACCAGTACATG-3’(SEQ ID NO:151)
5’-UGGGGAGGGCUUUCUUUGUGUAUUU-3’(SEQ ID NO:5155)
3'-UGACCCCUCCCGAAAGAAACACAUAAA-5'(SEQ ID NO:17)
KRAS-401靶:5'-ACTGGGGAGGGCTTTCTTTGTGTATTT-3’(SEQ ID NO:152)
5’-GGAGGGCUUUCUUUGUGUAUUUGCC-3’(SEQ ID NO:5156)
3'-CCCCUCCCGAAAGAAACACAUAAACGG-5'(SEQ ID NO:18)
KRAS-404靶:5'-GGGGAGGGCTTTCTTTGTGTATTTGCC-3’(SEQ ID NO:153)
5’-AGGGCUUUCUUUGUGUAUUUGCCAU-3’(SEQ ID NO:5157)
3'-CCUCCCGAAAGAAACACAUAAACGGUA-5'(SEQ ID NO:19)
KRAS-406靶:5'-GGAGGGCTTTCTTTGTGTATTTGCCAT-3’(SEQ ID NO:154)
5’-CUUUCUUUGUGUAUUUGCCAUAAAU-3’(SEQ ID NO:5158)
3'-CCGAAAGAAACACAUAAACGGUAUUUA-5'(SEQ ID NO:20)
KRAS-410靶:5'-GGCTTTCTTTGTGTATTTGCCATAAAT-3’(SEQ ID NO:155)
5’-UUUGUGUAUUUGCCAUAAAUAAUAC-3’(SEQ ID NO:5159)
3'-AGAAACACAUAAACGGUAUUUAUUAUG-5'(SEQ ID NO:21)
KRAS-415靶:5'-TCTTTGTGTATTTGCCATAAATAATAC-3’(SEQ ID NO:156)
5’-UUGUGUAUUUGCCAUAAAUAAUACU-3’(SEQ ID NO:5160)
3'-GAAACACAUAAACGGUAUUUAUUAUGA-5'(SEQ ID NO:22)
KRAS-416靶:5'-CTTTGTGTATTTGCCATAAATAATACT-3’(SEQ ID NO:157)
5’-UGUGUAUUUGCCAUAAAUAAUACUA-3’(SEQ ID NO:5161)
3'-AAACACAUAAACGGUAUUUAUUAUGAU-5'(SEQ ID NO:23)
KRAS-417靶:5'-TTTGTGTATTTGCCATAAATAATACTA-3’(SEQ ID NO:158)
5’-GUGUAUUUGCCAUAAAUAAUACUAA-3’(SEQ ID NO:5162)
3'-AACACAUAAACGGUAUUUAUUAUGAUU-5'(SEQ ID NO:24)
KRAS-418靶:5'-TTGTGTATTTGCCATAAATAATACTAA-3’(SEQ ID NO:159)
5’-UGUAUUUGCCAUAAAUAAUACUAAA-3’(SEQ ID NO:5163)
3'-ACACAUAAACGGUAUUUAUUAUGAUUU-5'(SEQ ID NO:25)
KRAS-419靶:5'-TGTGTATTTGCCATAAATAATACTAAA-3’(SEQ ID NO:160)
5’-GUAUUUGCCAUAAAUAAUACUAAAU-3’(SEQ ID NO:5164)
3'-CACAUAAACGGUAUUUAUUAUGAUUUA-5'(SEQ ID NO:26)
KRAS-420靶:5'-GTGTATTTGCCATAAATAATACTAAAT-3’(SEQ ID NO:161)
5’-AUAAAUAAUACUAAAUCAUUUGAAG-3’(SEQ ID NO:5165)
3'-GGUAUUUAUUAUGAUUUAGUAAACUUC-5'(SEQ ID NO:27)
KRAS-429靶:5'-CCATAAATAATACTAAATCATTTGAAG-3’(SEQ ID NO:162)
5’-UAAUACUAAAUCAUUUGAAGAUAUU-3’(SEQ ID NO:5166)
3'-UUAUUAUGAUUUAGUAAACUUCUAUAA-5'(SEQ ID NO:28)
KRAS-434靶:5'-AATAATACTAAATCATTTGAAGATATT-3’(SEQ ID NO:163)
5’-ACUAAAUCAUUUGAAGAUAUUCACC-3’(SEQ ID NO:5167)
3'-UAUGAUUUAGUAAACUUCUAUAAGUGG-5'(SEQ ID NO:29)
KRAS-438靶:5'-ATACTAAATCATTTGAAGATATTCACC-3’(SEQ ID NO:164)
5’-UAAAUCAUUUGAAGAUAUUCACCAU-3’(SEQ ID NO:5168)
3'-UGAUUUAGUAAACUUCUAUAAGUGGUA-5'(SEQ ID NO:30)
KRAS-440靶:5'-ACTAAATCATTTGAAGATATTCACCAT-3’(SEQ ID NO:165)
5’-CAUUUGAAGAUAUUCACCAUUAUAG-3’(SEQ ID NO:5169)
3'-UAGUAAACUUCUAUAAGUGGUAAUAUC-5'(SEQ ID NO:31)
KRAS-445靶:5'-ATCATTTGAAGATATTCACCATTATAG-3’(SEQ ID NO:166)
5’-GAAGAUAUUCACCAUUAUAGAGAAC-3’(SEQ ID NO:5170)
3'-AACUUCUAUAAGUGGUAAUAUCUCUUG-5'(SEQ ID NO:32)
KRAS-450靶:5'-TTGAAGATATTCACCATTATAGAGAAC-3’(SEQ ID NO:167)
5’-AGAUAUUCACCAUUAUAGAGAACAA-3’(SEQ ID NO:5171)
3'-CUUCUAUAAGUGGUAAUAUCUCUUGUU-5'(SEQ ID NO:33)
KRAS-452靶:5'-GAAGATATTCACCATTATAGAGAACAA-3’(SEQ ID NO:168)
5’-CUAUGGUCCUAGUAGGAAAUAAAUG-3’(SEQ ID NO:5172)
3'-UGGAUACCAGGAUCAUCCUUUAUUUAC-5'(SEQ ID NO:34)
KRAS-508靶:5'-ACCTATGGTCCTAGTAGGAAATAAATG-3’(SEQ ID NO:169)
5’-GAUUUGCCUUCUAGAACAGUAGACA-3’(SEQ ID NO:5173)
3'-CACUAAACGGAAGAUCUUGUCAUCUGU-5'(SEQ ID NO:35)
KRAS-534靶:5'-GTGATTTGCCTTCTAGAACAGTAGACA-3’(SEQ ID NO:170)
5’-GAUGAUGCCUUCUAUACAUUAGUUC-3’(SEQ ID NO:5174)
3'-AACUACUACGGAAGAUAUGUAAUCAAG-5'(SEQ ID NO:36)
KRAS-760靶:5'-TTGATGATGCCTTCTATACATTAGTTC-3’(SEQ ID NO:171)
5’-CAUUAGUUCGAGAAAUUCGAAAACA-3’(SEQ ID NO:5175)
3'-AUGUAAUCAAGCUCUUUAAGCUUUUGU-5'(SEQ ID NO:37)
KRAS-776靶:5'-TACATTAGTTCGAGAAATTCGAAAACA-3’(SEQ ID NO:172)
5’-AGAAAUUCGAAAACAUAAAGAAAAG-3’(SEQ ID NO:5176)
3'-GCUCUUUAAGCUUUUGUAUUUCUUUUC-5'(SEQ ID NO:38)
KRAS-786靶:5'-CGAGAAATTCGAAAACATAAAGAAAAG-3’(SEQ ID NO:173)
5’-AAAACAUAAAGAAAAGAUGAGCAAA-3’(SEQ ID NO:5177)
3'-GCUUUUGUAUUUCUUUUCUACUCGUUU-5'(SEQ ID NO:39)
KRAS-795靶:5'-CGAAAACATAAAGAAAAGATGAGCAAA-3’(SEQ ID NO:174)
5’-AUAAAGAAAAGAUGAGCAAAGAUGG-3’(SEQ ID NO:5178)
3'-UGUAUUUCUUUUCUACUCGUUUCUACC-5'(SEQ ID NO:40)
KRAS-800靶:5'-ACATAAAGAAAAGATGAGCAAAGATGG-3’(SEQ ID NO:175)
5’-AUAAAGAAAAGAUGAGCAAAGACGG-3’(SEQ ID NO:5179)
3'-UGUAUUUCUUUUCUACUCGUUUCUGCC-5'(SEQ ID NO:140)
KRAS-800*靶:5'-ACATAAAGAAAAGATGAGCAAAGACGG-3’(SEQ ID NO:176)
5’-UUGUACAUUACACUAAAUUAUUAGC-3’(SEQ ID NO:5180)
3'-AAAACAUGUAAUGUGAUUUAAUAAUCG-5'(SEQ ID NO:41)
KRAS-920靶:5'-TTTTGTACATTACACTAAATTATTAGC-3’(SEQ ID NO:177)
5’-AAUUAUUAGCAUUUGUUUUAGCAUU-3’(SEQ ID NO:5181)
3'-AUUUAAUAAUCGUAAACAAAAUCGUAA-5'(SEQ ID NO:42)
KRAS-935靶:5'-TAAATTATTAGCATTTGTTTTAGCATT-3’(SEQ ID NO:178)
5’-UUAGCAUUUGUUUUAGCAUUACCUA-3’(SEQ ID NO:5182)
3'-AUAAUCGUAAACAAAAUCGUAAUGGAU-5'(SEQ ID NO:43)
KRAS-940靶:5'-TATTAGCATTTGTTTTAGCATTACCTA-3’(SEQ ID NO:179)
5’-AGUUUUUUUUUCCUCUAAGUGCCAG-3’(SEQ ID NO:5183)
3'-CUUCAAAAAAAAAGGAGAUUCACGGUC-5'(SEQ ID NO:44)
KRAS-1032靶:5'-GAAGTTTTTTTTTCCTCTAAGTGCCAG-3’(SEQ ID NO:180)
5’-AAGUGCCAGUAUUCCCAGAGUUUUG-3’(SEQ ID NO:5184)
3'-GAUUCACGGUCAUAAGGGUCUCAAAAC-5'(SEQ ID NO:45)
KRAS-1048靶:5'-CTAAGTGCCAGTATTCCCAGAGTTTTG-3’(SEQ ID NO:181)
5’-GGUGUGAAACAAAUUAAUGAAGCUU-3’(SEQ ID NO:5185)
3'-AACCACACUUUGUUUAAUUACUUCGAA-5'(SEQ ID NO:46)
KRAS-1188靶:5'-TTGGTGTGAAACAAATTAATGAAGCTT-3’(SEQ ID NO:182)
5’-AUUAAUUACUAAUUUCAGUUGAGAC-3’(SEQ ID NO:5186)
3'-CCUAAUUAAUGAUUAAAGUCAACUCUG-5'(SEQ ID NO:47)
KRAS-1256靶:5'-GGATTAATTACTAATTTCAGTTGAGAC-3’(SEQ ID NO:183)
5’-UAUAUUUACAUGCUACUAAAUUUUU-3’(SEQ ID NO:5187)
3'-CGAUAUAAAUGUACGAUGAUUUAAAAA-5'(SEQ ID NO:48)
KRAS-1634靶:5'-GCTATATTTACATGCTACTAAATTTTT-3’(SEQ ID NO:184)
5’-UUUAACUAUUUUUGUAUAGUGUAAA-3’(SEQ ID NO:5188)
3'-UAAAAUUGAUAAAAACAUAUCACAUUU-5'(SEQ ID NO:49)
KRAS-5134靶:5'-ATTTTAACTATTTTTGTATAGTGTAAA-3’(SEQ ID NO:185)
5’-CAGUGUGAUCCAGUUGUUUUCCAUC-3’(SEQ ID NO:5189)
3'-ACGUCACACUAGGUCAACAAAAGGUAG-5'(SEQ ID NO:50)
KRAS-5208靶:5'-TGCAGTGTGATCCAGTTGTTTTCCATC-3’(SEQ ID NO:186)
5'-CUGAAAAUGACUGAAUAUAAACUUG-3'(SEQ ID NO:5190)
3'-ACGACUUUUACUGACUUAUAUUUGAAC-5'(SEQ ID NO:189)
KRAS-174靶:5'-TGCTGAAAATGACTGAATATAAACTTG-3'(SEQ ID NO:1595)
5'-AUGACUGAAUAUAAACUUGUGGUAG-3'(SEQ ID NO:5191)
3'-UUUACUGACUUAUAUUUGAACACCAUC-5'(SEQ ID NO:190)
KRAS-180靶:5'-AAATGACTGAATATAAACTTGTGGTAG-3'(SEQ ID NO:1596)
5'-CUGAAUAUAAACUUGUGGUAGUUGG-3'(SEQ ID NO:5192)
3'-CUGACUUAUAUUUGAACACCAUCAACC-5'(SEQ ID NO:191)
KRAS-184靶:5'-GACTGAATATAAACTTGTGGTAGTTGG-3'(SEQ ID NO:1597)
5'-CUAAUUCAGAAUCAUUUUGUGGACG-3'(SEQ ID NO:5193)
3'-UCGAUUAAGUCUUAGUAAAACACCUGC-5'(SEQ ID NO:192)
KRAS-246靶:5'-AGCTAATTCAGAATCATTTTGTGGACG-3'(SEQ ID NO:1598)
5'-GAAUAUGAUCCAACAAUAGAGGAUU-3'(SEQ ID NO:5194)
3'-UGCUUAUACUAGGUUGUUAUCUCCUAA-5'(SEQ ID NO:193)
KRAS-270靶:5'-ACGAATATGATCCAACAATAGAGGATT-3'(SEQ ID NO:1599)
5'-CAAGUAGUAAUUGAUGGAGAAACCU-3'(SEQ ID NO:5195)
3'-UCGUUCAUCAUUAACUACCUCUUUGGA-5'(SEQ ID NO:194)
KRAS-306靶:5'-AGCAAGTAGTAATTGATGGAGAAACCT-3'(SEQ ID NO:1600)
5'-AGGGCUUUCUUUGUGUAUUUGCCAU-3'(SEQ ID NO:5196)
3'-CCUCCCGAAAGAAACACAUAAACGGUA-5'(SEQ ID NO:195)
KRAS-406靶:5'-GGAGGGCTTTCTTTGTGTATTTGCCAT-3'(SEQ ID NO:1601)
5'-UUUGUGUAUUUGCCAUAAAUAAUAC-3'(SEQ ID NO:5197)
3'-AGAAACACAUAAACGGUAUUUAUUAUG-5'(SEQ ID NO:196)
KRAS-415靶:5'-TCTTTGTGTATTTGCCATAAATAATAC-3'(SEQ ID NO:1602)
5'-UUGUGUAUUUGCCAUAAAUAAUACU-3'(SEQ ID NO:5198)
3'-GAAACACAUAAACGGUAUUUAUUAUGA-5'(SEQ ID NO:197)
KRAS-416靶:5'-CTTTGTGTATTTGCCATAAATAATACT-3'(SEQ ID NO:1603)
5'-UGUGUAUUUGCCAUAAAUAAUACUA-3'(SEQ ID NO:5199)
3'-AAACACAUAAACGGUAUUUAUUAUGAU-5'(SEQ ID NO:198)
KRAS-417靶:5'-TTTGTGTATTTGCCATAAATAATACTA-3'(SEQ ID NO:1604)
5'-GUGUAUUUGCCAUAAAUAAUACUAA-3'(SEQ ID NO:5200)
3'-AACACAUAAACGGUAUUUAUUAUGAUU-5'(SEQ ID NO:199)
KRAS-418靶:5'-TTGTGTATTTGCCATAAATAATACTAA-3'(SEQ ID NO:1605)
5'-AUUUGCCAUAAAUAAUACUAAAUCA-3'(SEQ ID NO:5201)
3'-CAUAAACGGUAUUUAUUAUGAUUUAGU-5'(SEQ ID NO:200)
KRAS-422靶:5'-GTATTTGCCATAAATAATACTAAATCA-3'(SEQ ID NO:1606)
5'-UUUGCCAUAAAUAAUACUAAAUCAU-3'(SEQ ID NO:5202)
3'-AUAAACGGUAUUUAUUAUGAUUUAGUA-5'(SEQ ID NO:201)
KRAS-423靶:5'-TATTTGCCATAAATAATACTAAATCAT-3'(SEQ ID NO:1607)
5'-AUAAAUAAUACUAAAUCAUUUGAAG-3'(SEQ ID NO:5203)
3'-GGUAUUUAUUAUGAUUUAGUAAACUUC-5'(SEQ ID NO:202)
KRAS-429靶:5'-CCATAAATAATACTAAATCATTTGAAG-3'(SEQ ID NO:1608)
5'-UAAAUAAUACUAAAUCAUUUGAAGA-3'(SEQ ID NO:5204)
3'-GUAUUUAUUAUGAUUUAGUAAACUUCU-5'(SEQ ID NO:203)
KRAS-430靶:5'-CATAAATAATACTAAATCATTTGAAGA-3'(SEQ ID NO:1609)
5'-AAUAAUACUAAAUCAUUUGAAGAUA-3'(SEQ ID NO:5205)
3'-AUUUAUUAUGAUUUAGUAAACUUCUAU-5'(SEQ ID NO:204)
KRAS-432靶:5'-TAAATAATACTAAATCATTTGAAGATA-3'(SEQ ID NO:1610)
5'-AUAAUACUAAAUCAUUUGAAGAUAU-3'(SEQ ID NO:5206)
3'-UUUAUUAUGAUUUAGUAAACUUCUAUA-5'(SEQ ID NO:205)
KRAS-433靶:5'-AAATAATACTAAATCATTTGAAGATAT-3'(SEQ ID NO:1611)
5'-UAAUACUAAAUCAUUUGAAGAUAUU-3'(SEQ ID NO:5207)
3'-UUAUUAUGAUUUAGUAAACUUCUAUAA-5'(SEQ ID NO:206)
KRAS-434靶:5'-AATAATACTAAATCATTTGAAGATATT-3'(SEQ ID NO:1612)
5'-AAUACUAAAUCAUUUGAAGAUAUUC-3'(SEQ ID NO:5208)
3'-UAUUAUGAUUUAGUAAACUUCUAUAAG-5'(SEQ ID NO:207)
KRAS-435靶:5'-ATAATACTAAATCATTTGAAGATATTC-3'(SEQ ID NO:1613)
5'-UUGAAGAUAUUCACCAUUAUAGAGA-3'(SEQ ID NO:5209)
3'-UAAACUUCUAUAAGUGGUAAUAUCUCU-5'(SEQ ID NO:208)
KRAS-448靶:5'-ATTTGAAGATATTCACCATTATAGAGA-3'(SEQ ID NO:1614)
5'-GAAGAUAUUCACCAUUAUAGAGAAC-3'(SEQ ID NO:5210)
3'-AACUUCUAUAAGUGGUAAUAUCUCUUG-5'(SEQ ID NO:209)
KRAS-450靶:5'-TTGAAGATATTCACCATTATAGAGAAC-3'(SEQ ID NO:1615)
5'-AAGAUAUUCACCAUUAUAGAGAACA-3'(SEQ ID NO:5211)
3'-ACUUCUAUAAGUGGUAAUAUCUCUUGU-5'(SEQ ID NO:210)
KRAS-451靶:5'-TGAAGATATTCACCATTATAGAGAACA-3'(SEQ ID NO:1616)
5'-AGAUAUUCACCAUUAUAGAGAACAA-3'(SEQ ID NO:5212)
3'-CUUCUAUAAGUGGUAAUAUCUCUUGUU-5'(SEQ ID NO:211)
KRAS-452靶:5'-GAAGATATTCACCATTATAGAGAACAA-3'(SEQ ID NO:1617)
5'-GAUAUUCACCAUUAUAGAGAACAAA-3'(SEQ ID NO:5213)
3'-UUCUAUAAGUGGUAAUAUCUCUUGUUU-5'(SEQ ID NO:212)
KRAS-453靶:5'-AAGATATTCACCATTATAGAGAACAAA-3'(SEQ ID NO:1618)
5'-AUUAUAGAGAACAAAUUAAAAGAGU-3'(SEQ ID NO:5214)
3'-GGUAAUAUCUCUUGUUUAAUUUUCUCA-5'(SEQ ID NO:213)
KRAS-463靶:5'-CCATTATAGAGAACAAATTAAAAGAGT-3'(SEQ ID NO:1619)
5'-UAUAGAGAACAAAUUAAAAGAGUUA-3'(SEQ ID NO:5215)
3'-UAAUAUCUCUUGUUUAAUUUUCUCAAU-5'(SEQ ID NO:214)
KRAS-465靶:5'-ATTATAGAGAACAAATTAAAAGAGTTA-3'(SEQ ID NO:1620)
5'-AUAGAGAACAAAUUAAAAGAGUUAA-3'(SEQ ID NO:5216)
3'-AAUAUCUCUUGUUUAAUUUUCUCAAUU-5'(SEQ ID NO:215)
KRAS-466靶:5'-TTATAGAGAACAAATTAAAAGAGTTAA-3'(SEQ ID NO:1621)
5'-UAGAGAACAAAUUAAAAGAGUUAAG-3'(SEQ ID NO:5217)
3'-AUAUCUCUUGUUUAAUUUUCUCAAUUC-5'(SEQ ID NO:216)
KRAS-467靶:5'-TATAGAGAACAAATTAAAAGAGTTAAG-3'(SEQ ID NO:1622)
5'-AGAGAACAAAUUAAAAGAGUUAAGG-3'(SEQ ID NO:5218)
3'-UAUCUCUUGUUUAAUUUUCUCAAUUCC-5'(SEQ ID NO:217)
KRAS-468靶:5'-ATAGAGAACAAATTAAAAGAGTTAAGG-3'(SEQ ID NO:1623)
5'-AGUAGGAAAUAAAUGUGAUUUGCCU-3'(SEQ ID NO:5219)
3'-GAUCAUCCUUUAUUUACACUAAACGGA-5'(SEQ ID NO:218)
KRAS-518靶:5'-CTAGTAGGAAATAAATGTGATTTGCCT-3'(SEQ ID NO:1624)
5'-GUAGGAAAUAAAUGUGAUUUGCCUU-3'(SEQ ID NO:5220)
3'-AUCAUCCUUUAUUUACACUAAACGGAA-5'(SEQ ID NO:219)
KRAS-519靶:5'-TAGTAGGAAATAAATGTGATTTGCCTT-3'(SEQ ID NO:1625)
5'-GAAGUUAUGGAAUUCCUUUUAUUGA-3'(SEQ ID NO:5221)
3'-UUCUUCAAUACCUUAAGGAAAAUAACU-5'(SEQ ID NO:220)
KRAS-583靶:5'-AAGAAGTTATGGAATTCCTTTTATTGA-3'(SEQ ID NO:1626)
5'-GUUAUGGAAUUCCUUUUAUUGAAAC-3'(SEQ ID NO:5222)
3'-UUCAAUACCUUAAGGAAAAUAACUUUG-5'(SEQ ID NO:221)
KRAS-586靶:5'-AAGTTATGGAATTCCTTTTATTGAAAC-3'(SEQ ID NO:1627)
5'-UUAUGGAAUUCCUUUUAUUGAAACA-3'(SEQ ID NO:5223)
3'-UCAAUACCUUAAGGAAAAUAACUUUGU-5'(SEQ ID NO:222)
KRAS-587靶:5'-AGTTATGGAATTCCTTTTATTGAAACA-3'(SEQ ID NO:1628)
5'-UAUGGAAUUCCUUUUAUUGAAACAU-3'(SEQ ID NO:5224)
3'-CAAUACCUUAAGGAAAAUAACUUUGUA-5'(SEQ ID NO:223)
KRAS-588靶:5'-GTTATGGAATTCCTTTTATTGAAACAT-3'(SEQ ID NO:1629)
5'-AUGGAAUUCCUUUUAUUGAAACAUC-3'(SEQ ID NO:5225)
3'-AAUACCUUAAGGAAAAUAACUUUGUAG-5'(SEQ ID NO:224)
KRAS-589靶:5'-TTATGGAATTCCTTTTATTGAAACATC-3'(SEQ ID NO:1630)
5'-GAGGAUGCUUUUUAUACAUUGGUGA-3'(SEQ ID NO:5226)
3'-ACCUCCUACGAAAAAUAUGUAACCACU-5'(SEQ ID NO:225)
KRAS-636靶:5'-TGGAGGATGCTTTTTATACATTGGTGA-3'(SEQ ID NO:1631)
5'-GGAUGCUUUUUAUACAUUGGUGAGG-3'(SEQ ID NO:5227)
3'-CUCCUACGAAAAAUAUGUAACCACUCC-5'(SEQ ID NO:226)
KRAS-638靶:5'-GAGGATGCTTTTTATACATTGGTGAGG-3'(SEQ ID NO:1632)
5'-AGAUUGAAAAAAAUCAGCAAAGAAG-3'(SEQ ID NO:5228)
3'-UGUCUAACUUUUUUUAGUCGUUUCUUC-5'(SEQ ID NO:227)
KRAS-678靶:5'-ACAGATTGAAAAAAATCAGCAAAGAAG-3'(SEQ ID NO:1633)
5'-GAUUGAAAAAAAUCAGCAAAGAAGA-3'(SEQ ID NO:5229)
3'-GUCUAACUUUUUUUAGUCGUUUCUUCU-5'(SEQ ID NO:228)
KRAS-679靶:5'-CAGATTGAAAAAAATCAGCAAAGAAGA-3'(SEQ ID NO:1634)
5'-UUGAAAAAAAUCAGCAAAGAAGAAA-3'(SEQ ID NO:5230)
3'-CUAACUUUUUUUAGUCGUUUCUUCUUU-5'(SEQ ID NO:229)
KRAS-681靶:5'-GATTGAAAAAAATCAGCAAAGAAGAAA-3'(SEQ ID NO:1635)
5'-UGAAAAAAAUCAGCAAAGAAGAAAA-3'(SEQ ID NO:5231)
3'-UAACUUUUUUUAGUCGUUUCUUCUUUU-5'(SEQ ID NO:230)
KRAS-682靶:5'-ATTGAAAAAAATCAGCAAAGAAGAAAA-3'(SEQ ID NO:1636)
5'-GAAAAAAAUCAGCAAAGAAGAAAAG-3'(SEQ ID NO:5232)
3'-AACUUUUUUUAGUCGUUUCUUCUUUUC-5'(SEQ ID NO:231)
KRAS-683靶:5'-TTGAAAAAAATCAGCAAAGAAGAAAAG-3'(SEQ ID NO:1637)
5'-AAAAAAAUCAGCAAAGAAGAAAAGA-3'(SEQ ID NO:5233)
3'-ACUUUUUUUAGUCGUUUCUUCUUUUCU-5'(SEQ ID NO:232)
KRAS-684靶:5'-TGAAAAAAATCAGCAAAGAAGAAAAGA-3'(SEQ ID NO:1638)
5'-CUGGCUGUGUGAAAAUUAAAAAAUG-3'(SEQ ID NO:5234)
3'-AGGACCGACACACUUUUAAUUUUUUAC-5'(SEQ ID NO:233)
KRAS-712靶:5'-TCCTGGCTGTGTGAAAATTAAAAAATG-3'(SEQ ID NO:1639)
5'-CUGUGUGAAAAUUAAAAAAUGCAUU-3'(SEQ ID NO:5235)
3'-CCGACACACUUUUAAUUUUUUACGUAA-5'(SEQ ID NO:234)
KRAS-716靶:5'-GGCTGTGTGAAAATTAAAAAATGCATT-3'(SEQ ID NO:1640)
5'-GUGAAAAUUAAAAAAUGCAUUAUAA-3'(SEQ ID NO:5236)
3'-CACACUUUUAAUUUUUUACGUAAUAUU-5'(SEQ ID NO:235)
KRAS-720靶:5'-GTGTGAAAATTAAAAAATGCATTATAA-3'(SEQ ID NO:1641)
5'-UGAAAAUUAAAAAAUGCAUUAUAAU-3'(SEQ ID NO:5237)
3'-ACACUUUUAAUUUUUUACGUAAUAUUA-5'(SEQ ID NO:236)
KRAS-721靶:5'-TGTGAAAATTAAAAAATGCATTATAAT-3'(SEQ ID NO:1642)
5'-GAAAAUUAAAAAAUGCAUUAUAAUG-3'(SEQ ID NO:5238)
3'-CACUUUUAAUUUUUUACGUAAUAUUAC-5'(SEQ ID NO:237)
KRAS-722靶:5'-GTGAAAATTAAAAAATGCATTATAATG-3'(SEQ ID NO:1643)
5'-AAAAUUAAAAAAUGCAUUAUAAUGU-3'(SEQ ID NO:5239)
3'-ACUUUUAAUUUUUUACGUAAUAUUACA-5'(SEQ ID NO:238)
KRAS-723靶:5'-TGAAAATTAAAAAATGCATTATAATGT-3'(SEQ ID NO:1644)
5'-AAUUAAAAAAUGCAUUAUAAUGUAA-3'(SEQ ID NO:5240)
3'-UUUUAAUUUUUUACGUAAUAUUACAUU-5'(SEQ ID NO:239)
KRAS-725靶:5'-AAAATTAAAAAATGCATTATAATGTAA-3'(SEQ ID NO:1645)
5'-AUUAAAAAAUGCAUUAUAAUGUAAU-3'(SEQ ID NO:5241)
3'-UUUAAUUUUUUACGUAAUAUUACAUUA-5'(SEQ ID NO:240)
KRAS-726靶:5'-AAATTAAAAAATGCATTATAATGTAAT-3'(SEQ ID NO:1646)
5'-UUAAAAAAUGCAUUAUAAUGUAAUC-3'(SEQ ID NO:5242)
3'-UUAAUUUUUUACGUAAUAUUACAUUAG-5'(SEQ ID NO:241)
KRAS-727靶:5'-AATTAAAAAATGCATTATAATGTAATC-3'(SEQ ID NO:1647)
5'-UAAAAAAUGCAUUAUAAUGUAAUCU-3'(SEQ ID NO:5243)
3'-UAAUUUUUUACGUAAUAUUACAUUAGA-5'(SEQ ID NO:242)
KRAS-728靶:5'-ATTAAAAAATGCATTATAATGTAATCT-3'(SEQ ID NO:1648)
5'-AAAAAUGCAUUAUAAUGUAAUCUGG-3'(SEQ ID NO:5244)
3'-AUUUUUUACGUAAUAUUACAUUAGACC-5'(SEQ ID NO:243)
KRAS-730靶:5'-TAAAAAATGCATTATAATGTAATCTGG-3'(SEQ ID NO:1649)
5'-CAUUAUAAUGUAAUCUGGGUGUUGA-3'(SEQ ID NO:5245)
3'-ACGUAAUAUUACAUUAGACCCACAACU-5'(SEQ ID NO:244)
KRAS-737靶:5'-TGCATTATAATGTAATCTGGGTGTTGA-3'(SEQ ID NO:1650)
5'-CGAGAAAUUCGAAAACAUAAAGAAA-3'(SEQ ID NO:5246)
3'-AAGCUCUUUAAGCUUUUGUAUUUCUUU-5'(SEQ ID NO:245)
KRAS-784靶:5'-TTCGAGAAATTCGAAAACATAAAGAAA-3'(SEQ ID NO:1651)
5'-GAGAAAUUCGAAAACAUAAAGAAAA-3'(SEQ ID NO:5247)
3'-AGCUCUUUAAGCUUUUGUAUUUCUUUU-5'(SEQ ID NO:246)
KRAS-785靶:5'-TCGAGAAATTCGAAAACATAAAGAAAA-3'(SEQ ID NO:1652)
5'-AGAAAUUCGAAAACAUAAAGAAAAG-3'(SEQ ID NO:5248)
3'-GCUCUUUAAGCUUUUGUAUUUCUUUUC-5'(SEQ ID NO:247)
KRAS-786靶:5'-CGAGAAATTCGAAAACATAAAGAAAAG-3'(SEQ ID NO:1653)
5'-AAUUCGAAAACAUAAAGAAAAGAUG-3'(SEQ ID NO:5249)
3'-CUUUAAGCUUUUGUAUUUCUUUUCUAC-5'(SEQ ID NO:248)
KRAS-789靶:5'-GAAATTCGAAAACATAAAGAAAAGATG-3'(SEQ ID NO:1654)
5'-GAAAACAUAAAGAAAAGAUGAGCAA-3'(SEQ ID NO:5250)
3'-AGCUUUUGUAUUUCUUUUCUACUCGUU-5'(SEQ ID NO:249)
KRAS-794靶:5'-TCGAAAACATAAAGAAAAGATGAGCAA-3'(SEQ ID NO:1655)
5'-AAAACAUAAAGAAAAGAUGAGCAAA-3'(SEQ ID NO:5251)
3'-GCUUUUGUAUUUCUUUUCUACUCGUUU-5'(SEQ ID NO:250)
KRAS-795靶:5'-CGAAAACATAAAGAAAAGATGAGCAAA-3'(SEQ ID NO:1656)
5'-AGAUGGUAAAAAGAAGAAAAAGAAG-3'(SEQ ID NO:5252)
3'-UUUCUACCAUUUUUCUUCUUUUUCUUC-5'(SEQ ID NO:251)
KRAS-819靶:5'-AAAGATGGTAAAAAGAAGAAAAAGAAG-3'(SEQ ID NO:1657)
5'-GAUGGUAAAAAGAAGAAAAAGAAGU-3'(SEQ ID NO:5253)
3'-UUCUACCAUUUUUCUUCUUUUUCUUCA-5'(SEQ ID NO:252)
KRAS-820靶:5'-AAGATGGTAAAAAGAAGAAAAAGAAGT-3'(SEQ ID NO:1658)
5'-UGGUAAAAAGAAGAAAAAGAAGUCA-3'(SEQ ID NO:5254)
3'-CUACCAUUUUUCUUCUUUUUCUUCAGU-5'(SEQ ID NO:253)
KRAS-822靶:5'-GATGGTAAAAAGAAGAAAAAGAAGTCA-3'(SEQ ID NO:1659)
5'-GGUAAAAAGAAGAAAAAGAAGUCAA-3'(SEQ ID NO:5255)
3'-UACCAUUUUUCUUCUUUUUCUUCAGUU-5'(SEQ ID NO:254)
KRAS-823靶:5'-ATGGTAAAAAGAAGAAAAAGAAGTCAA-3'(SEQ ID NO:1660)
5'-AAAGAAGAAAAAGAAGUCAAAGACA-3'(SEQ ID NO:5256)
3'-UUUUUCUUCUUUUUCUUCAGUUUCUGU-5'(SEQ ID NO:255)
KRAS-828靶:5'-AAAAAGAAGAAAAAGAAGTCAAAGACA-3'(SEQ ID NO:1661)
5'-AAGAAGAAAAAGAAGUCAAAGACAA-3'(SEQ ID NO:5257)
3'-UUUUCUUCUUUUUCUUCAGUUUCUGUU-5'(SEQ ID NO:256)
KRAS-829靶:5'-AAAAGAAGAAAAAGAAGTCAAAGACAA-3'(SEQ ID NO:1662)
5'-AGAAGAAAAAGAAGUCAAAGACAAA-3'(SEQ ID NO:5258)
3'-UUUCUUCUUUUUCUUCAGUUUCUGUUU-5'(SEQ ID NO:257)
KRAS-830靶:5'-AAAGAAGAAAAAGAAGTCAAAGACAAA-3'(SEQ ID NO:1663)
5'-AAAGACAAAGUGUGUAAUUAUGUAA-3'(SEQ ID NO:5259)
3'-AGUUUCUGUUUCACACAUUAAUACAUU-5'(SEQ ID NO:258)
KRAS-846靶:5'-TCAAAGACAAAGTGTGTAATTATGTAA-3'(SEQ ID NO:1664)
5'-AAGACAAAGUGUGUAAUUAUGUAAA-3'(SEQ ID NO:5260)
3'-GUUUCUGUUUCACACAUUAAUACAUUU-5'(SEQ ID NO:259)
KRAS-847靶:5'-CAAAGACAAAGTGTGTAATTATGTAAA-3'(SEQ ID NO:1665)
5'-CAAAGUGUGUAAUUAUGUAAAUACA-3'(SEQ ID NO:5261)
3'-CUGUUUCACACAUUAAUACAUUUAUGU-5'(SEQ ID NO:260)
KRAS-851靶:5'-GACAAAGTGTGTAATTATGTAAATACA-3'(SEQ ID NO:1666)
5'-AAGUGUGUAAUUAUGUAAAUACAAU-3'(SEQ ID NO:5262)
3'-GUUUCACACAUUAAUACAUUUAUGUUA-5'(SEQ ID NO:261)
KRAS-853靶:5'-CAAAGTGTGTAATTATGTAAATACAAT-3'(SEQ ID NO:1667)
5'-GUGUAAUUAUGUAAAUACAAUUUGU-3'(SEQ ID NO:5263)
3'-CACACAUUAAUACAUUUAUGUUAAACA-5'(SEQ ID NO:262)
KRAS-857靶:5'-GTGTGTAATTATGTAAATACAATTTGT-3'(SEQ ID NO:1668)
5'-GUAAUUAUGUAAAUACAAUUUGUAC-3'(SEQ ID NO:5264)
3'-CACAUUAAUACAUUUAUGUUAAACAUG-5'(SEQ ID NO:263)
KRAS-859靶:5'-GTGTAATTATGTAAATACAATTTGTAC-3'(SEQ ID NO:1669)
5'-AAUUAUGUAAAUACAAUUUGUACUU-3'(SEQ ID NO:5265)
3'-CAUUAAUACAUUUAUGUUAAACAUGAA-5'(SEQ ID NO:264)
KRAS-861靶:5'-GTAATTATGTAAATACAATTTGTACTT-3'(SEQ ID NO:1670)
5'-AUUAUGUAAAUACAAUUUGUACUUU-3'(SEQ ID NO:5266)
3'-AUUAAUACAUUUAUGUUAAACAUGAAA-5'(SEQ ID NO:265)
KRAS-862靶:5'-TAATTATGTAAATACAATTTGTACTTT-3'(SEQ ID NO:1671)
5'-UGUAAAUACAAUUUGUACUUUUUUC-3'(SEQ ID NO:5267)
3'-AUACAUUUAUGUUAAACAUGAAAAAAG-5'(SEQ ID NO:266)
KRAS-866靶:5'-TATGTAAATACAATTTGTACTTTTTTC-3'(SEQ ID NO:1672)
5'-GUAAAUACAAUUUGUACUUUUUUCU-3'(SEQ ID NO:5268)
3'-UACAUUUAUGUUAAACAUGAAAAAAGA-5'(SEQ ID NO:267)
KRAS-867靶:5'-ATGTAAATACAATTTGTACTTTTTTCT-3'(SEQ ID NO:1673)
5'-UAAAUACAAUUUGUACUUUUUUCUU-3'(SEQ ID NO:5269)
3'-ACAUUUAUGUUAAACAUGAAAAAAGAA-5'(SEQ ID NO:268)
KRAS-868靶:5'-TGTAAATACAATTTGTACTTTTTTCTT-3'(SEQ ID NO:1674)
5'-AAAUACAAUUUGUACUUUUUUCUUA-3'(SEQ ID NO:5270)
3'-CAUUUAUGUUAAACAUGAAAAAAGAAU-5'(SEQ ID NO:269)
KRAS-869靶:5'-GTAAATACAATTTGTACTTTTTTCTTA-3'(SEQ ID NO:1675)
5'-AAUUUGUACUUUUUUCUUAAGGCAU-3'(SEQ ID NO:5271)
3'-UGUUAAACAUGAAAAAAGAAUUCCGUA-5'(SEQ ID NO:270)
KRAS-875靶:5'-ACAATTTGTACTTTTTTCTTAAGGCAT-3'(SEQ ID NO:1676)
5'-AUUUGUACUUUUUUCUUAAGGCAUA-3'(SEQ ID NO:5272)
3'-GUUAAACAUGAAAAAAGAAUUCCGUAU-5'(SEQ ID NO:271)
KRAS-876靶:5'-CAATTTGTACTTTTTTCTTAAGGCATA-3'(SEQ ID NO:1677)
5'-CUAGUACAAGUGGUAAUUUUUGUAC-3'(SEQ ID NO:5273)
3'-AUGAUCAUGUUCACCAUUAAAAACAUG-5'(SEQ ID NO:272)
KRAS-901靶:5'-TACTAGTACAAGTGGTAATTTTTGTAC-3'(SEQ ID NO:1678)
5'-UAGUACAAGUGGUAAUUUUUGUACA-3'(SEQ ID NO:5274)
3'-UGAUCAUGUUCACCAUUAAAAACAUGU-5'(SEQ ID NO:273)
KRAS-902靶:5'-ACTAGTACAAGTGGTAATTTTTGTACA-3'(SEQ ID NO:1679)
5'-AAGUGGUAAUUUUUGUACAUUACAC-3'(SEQ ID NO:5275)
3'-UGUUCACCAUUAAAAACAUGUAAUGUG-5'(SEQ ID NO:274)
KRAS-908靶:5'-ACAAGTGGTAATTTTTGTACATTACAC-3'(SEQ ID NO:1680)
5'-AGUGGUAAUUUUUGUACAUUACACU-3'(SEQ ID NO:5276)
3'-GUUCACCAUUAAAAACAUGUAAUGUGA-5'(SEQ ID NO:275)
KRAS-909靶:5'-CAAGTGGTAATTTTTGTACATTACACT-3'(SEQ ID NO:1681)
5'-AUUUUUGUACAUUACACUAAAUUAU-3'(SEQ ID NO:5277)
3'-AUUAAAAACAUGUAAUGUGAUUUAAUA-5'(SEQ ID NO:276)
KRAS-916靶:5'-TAATTTTTGTACATTACACTAAATTAT-3'(SEQ ID NO:1682)
5'-UUUUUGUACAUUACACUAAAUUAUU-3'(SEQ ID NO:5278)
3'-UUAAAAACAUGUAAUGUGAUUUAAUAA-5'(SEQ ID NO:277)
KRAS-917靶:5'-AATTTTTGTACATTACACTAAATTATT-3'(SEQ ID NO:1683)
5'-UUUUGUACAUUACACUAAAUUAUUA-3'(SEQ ID NO:5279)
3'-UAAAAACAUGUAAUGUGAUUUAAUAAU-5'(SEQ ID NO:278)
KRAS-918靶:5'-ATTTTTGTACATTACACTAAATTATTA-3'(SEQ ID NO:1684)
5'-UUUGUACAUUACACUAAAUUAUUAG-3'(SEQ ID NO:5280)
3'-AAAAACAUGUAAUGUGAUUUAAUAAUC-5'(SEQ ID NO:279)
KRAS-919靶:5'-TTTTTGTACATTACACTAAATTATTAG-3'(SEQ ID NO:1685)
5'-UUGUACAUUACACUAAAUUAUUAGC-3'(SEQ ID NO:5281)
3'-AAAACAUGUAAUGUGAUUUAAUAAUCG-5'(SEQ ID NO:280)
KRAS-920靶:5'-TTTTGTACATTACACTAAATTATTAGC-3'(SEQ ID NO:1686)
5'-CUAAAUUAUUAGCAUUUGUUUUAGC-3'(SEQ ID NO:5282)
3'-GUGAUUUAAUAAUCGUAAACAAAAUCG-5'(SEQ ID NO:281)
KRAS-932靶:5'-CACTAAATTATTAGCATTTGTTTTAGC-3'(SEQ ID NO:1687)
5'-AAAUUAUUAGCAUUUGUUUUAGCAU-3'(SEQ ID NO:5283)
3'-GAUUUAAUAAUCGUAAACAAAAUCGUA-5'(SEQ ID NO:282)
KRAS-934靶:5'-CTAAATTATTAGCATTTGTTTTAGCAT-3'(SEQ ID NO:1688)
5'-AAUUAUUAGCAUUUGUUUUAGCAUU-3'(SEQ ID NO:5284)
3'-AUUUAAUAAUCGUAAACAAAAUCGUAA-5'(SEQ ID NO:283)
KRAS-935靶:5'-TAAATTATTAGCATTTGTTTTAGCATT-3'(SEQ ID NO:1689)
5'-UUAGCAUUUGUUUUAGCAUUACCUA-3'(SEQ ID NO:5285)
3'-AUAAUCGUAAACAAAAUCGUAAUGGAU-5'(SEQ ID NO:284)
KRAS-940靶:5'-TATTAGCATTTGTTTTAGCATTACCTA-3'(SEQ ID NO:1690)
5'-UUUGUUUUAGCAUUACCUAAUUUUU-3'(SEQ ID NO:5286)
3'-GUAAACAAAAUCGUAAUGGAUUAAAAA-5'(SEQ ID NO:285)
KRAS-946靶:5'-CATTTGTTTTAGCATTACCTAATTTTT-3'(SEQ ID NO:1691)
5'-UUGUUUUAGCAUUACCUAAUUUUUU-3'(SEQ ID NO:5287)
3'-UAAACAAAAUCGUAAUGGAUUAAAAAA-5'(SEQ ID NO:286)
KRAS-947靶:5'-ATTTGTTTTAGCATTACCTAATTTTTT-3'(SEQ ID NO:1692)
5'-GUUUUAGCAUUACCUAAUUUUUUUC-3'(SEQ ID NO:5288)
3'-AACAAAAUCGUAAUGGAUUAAAAAAAG-5'(SEQ ID NO:287)
KRAS-949靶:5'-TTGTTTTAGCATTACCTAATTTTTTTC-3'(SEQ ID NO:1693)
5'-UUUUAGCAUUACCUAAUUUUUUUCC-3'(SEQ ID NO:5289)
3'-ACAAAAUCGUAAUGGAUUAAAAAAAGG-5'(SEQ ID NO:288)
KRAS-950靶:5'-TGTTTTAGCATTACCTAATTTTTTTCC-3'(SEQ ID NO:1694)
5'-UUUAGCAUUACCUAAUUUUUUUCCU-3'(SEQ ID NO:5290)
3'-CAAAAUCGUAAUGGAUUAAAAAAAGGA-5'(SEQ ID NO:289)
KRAS-951靶:5'-GTTTTAGCATTACCTAATTTTTTTCCT-3'(SEQ ID NO:1695)
5'-UUAGCAUUACCUAAUUUUUUUCCUG-3'(SEQ ID NO:5291)
3'-AAAAUCGUAAUGGAUUAAAAAAAGGAC-5'(SEQ ID NO:290)
KRAS-952靶:5'-TTTTAGCATTACCTAATTTTTTTCCTG-3'(SEQ ID NO:1696)
5'-CUGUUAGCUUUUACCUUAAAUGCUU-3'(SEQ ID NO:5292)
3'-CUGACAAUCGAAAAUGGAAUUUACGAA-5'(SEQ ID NO:291)
KRAS-988靶:5'-GACTGTTAGCTTTTACCTTAAATGCTT-3'(SEQ ID NO:1697)
5'-UGUUAGCUUUUACCUUAAAUGCUUA-3'(SEQ ID NO:5293)
3'-UGACAAUCGAAAAUGGAAUUUACGAAU-5'(SEQ ID NO:292)
KRAS-989靶:5'-ACTGTTAGCTTTTACCTTAAATGCTTA-3'(SEQ ID NO:1698)
5'-CUUUUACCUUAAAUGCUUAUUUUAA-3'(SEQ ID NO:5294)
3'-UCGAAAAUGGAAUUUACGAAUAAAAUU-5'(SEQ ID NO:293)
KRAS-995靶:5'-AGCTTTTACCTTAAATGCTTATTTTAA-3'(SEQ ID NO:1699)
5'-UUUUACCUUAAAUGCUUAUUUUAAA-3'(SEQ ID NO:5295)
3'-CGAAAAUGGAAUUUACGAAUAAAAUUU-5'(SEQ ID NO:294)
KRAS-996靶:5'-GCTTTTACCTTAAATGCTTATTTTAAA-3'(SEQ ID NO:1700)
5'-UUUACCUUAAAUGCUUAUUUUAAAA-3'(SEQ ID NO:5296)
3'-GAAAAUGGAAUUUACGAAUAAAAUUUU-5'(SEQ ID NO:295)
KRAS-997靶:5'-CTTTTACCTTAAATGCTTATTTTAAAA-3'(SEQ ID NO:1701)
5'-UUAAAUGCUUAUUUUAAAAUGACAG-3'(SEQ ID NO:5297)
3'-GGAAUUUACGAAUAAAAUUUUACUGUC-5'(SEQ ID NO:296)
KRAS-1003靶:5'-CCTTAAATGCTTATTTTAAAATGACAG-3'(SEQ ID NO:1702)
5'-UAAAUGCUUAUUUUAAAAUGACAGU-3'(SEQ ID NO:5298)
3'-GAAUUUACGAAUAAAAUUUUACUGUCA-5'(SEQ ID NO:297)
KRAS-1004靶:5'-CTTAAATGCTTATTTTAAAATGACAGT-3'(SEQ ID NO:1703)
5'-CUUAUUUUAAAAUGACAGUGGAAGU-3'(SEQ ID NO:5299)
3'-ACGAAUAAAAUUUUACUGUCACCUUCA-5'(SEQ ID NO:298)
KRAS-1010靶:5'-TGCTTATTTTAAAATGACAGTGGAAGT-3'(SEQ ID NO:1704)
5'-UAUUUUAAAAUGACAGUGGAAGUUU-3'(SEQ ID NO:5300)
3'-GAAUAAAAUUUUACUGUCACCUUCAAA-5'(SEQ ID NO:299)
KRAS-1012靶:5'-CTTATTTTAAAATGACAGTGGAAGTTT-3'(SEQ ID NO:1705)
5'-GGAAGUUUUUUUUUCCUCUAAGUGC-3'(SEQ ID NO:5301)
3'-CACCUUCAAAAAAAAAGGAGAUUCACG-5'(SEQ ID NO:300)
KRAS-1029靶:5'-GTGGAAGTTTTTTTTTCCTCTAAGTGC-3'(SEQ ID NO:1706)
5'-AAGUUUUUUUUUCCUCUAAGUGCCA-3'(SEQ ID NO:5302)
3'-CCUUCAAAAAAAAAGGAGAUUCACGGU-5'(SEQ ID NO:301)
KRAS-1031靶:5'-GGAAGTTTTTTTTTCCTCTAAGTGCCA-3'(SEQ ID NO:1707)
5'-AGUUUUUUUUUCCUCUAAGUGCCAG-3'(SEQ ID NO:5303)
3'-CUUCAAAAAAAAAGGAGAUUCACGGUC-5'(SEQ ID NO:302)
KRAS-1032靶:5'-GAAGTTTTTTTTTCCTCTAAGTGCCAG-3'(SEQ ID NO:1708)
5'-UUGGUUUUUGAACUAGCAAUGCCUG-3'(SEQ ID NO:5304)
3'-AAAACCAAAAACUUGAUCGUUACGGAC-5'(SEQ ID NO:303)
KRAS-1070靶:5'-TTTTGGTTTTTGAACTAGCAATGCCTG-3'(SEQ ID NO:1709)
5'-CUGUGAAAAAGAAACUGAAUACCUA-3'(SEQ ID NO:5305)
3'-CGGACACUUUUUCUUUGACUUAUGGAU-5'(SEQ ID NO:304)
KRAS-1092靶:5'-GCCTGTGAAAAAGAAACTGAATACCTA-3'(SEQ ID NO:1710)
5'-AAAGAAACUGAAUACCUAAGAUUUC-3'(SEQ ID NO:5306)
3'-UUUUUCUUUGACUUAUGGAUUCUAAAG-5'(SEQ ID NO:305)
KRAS-1099靶:5'-AAAAAGAAACTGAATACCTAAGATTTC-3'(SEQ ID NO:1711)
5'-AAGAAACUGAAUACCUAAGAUUUCU-3'(SEQ ID NO:5307)
3'-UUUUCUUUGACUUAUGGAUUCUAAAGA-5'(SEQ ID NO:306)
KRAS-1100靶:5'-AAAAGAAACTGAATACCTAAGATTTCT-3'(SEQ ID NO:1712)
5'-CUGAAUACCUAAGAUUUCUGUCUUG-3'(SEQ ID NO:5308)
3'-UUGACUUAUGGAUUCUAAAGACAGAAC-5'(SEQ ID NO:307)
KRAS-1106靶:5'-AACTGAATACCTAAGATTTCTGTCTTG-3'(SEQ ID NO:1713)
5'-CAGUUGAUUACUUCUUAUUUUUCUU-3'(SEQ ID NO:5309)
3'-ACGUCAACUAAUGAAGAAUAAAAAGAA-5'(SEQ ID NO:308)
KRAS-1147靶:5'-TGCAGTTGATTACTTCTTATTTTTCTT-3'(SEQ ID NO:1714)
5'-AGUUGAUUACUUCUUAUUUUUCUUA-3'(SEQ ID NO:5310)
3'-CGUCAACUAAUGAAGAAUAAAAAGAAU-5'(SEQ ID NO:309)
KRAS-1148靶:5'-GCAGTTGATTACTTCTTATTTTTCTTA-3'(SEQ ID NO:1715)
5'-GAUUACUUCUUAUUUUUCUUACCAA-3'(SEQ ID NO:5311)
3'-AACUAAUGAAGAAUAAAAAGAAUGGUU-5'(SEQ ID NO:310)
KRAS-1152靶:5'-TTGATTACTTCTTATTTTTCTTACCAA-3'(SEQ ID NO:1716)
5'-CUUAUUUUUCUUACCAAUUGUGAAU-3'(SEQ ID NO:5312)
3'-AAGAAUAAAAAGAAUGGUUAACACUUA-5'(SEQ ID NO:311)
KRAS-1160靶:5'-TTCTTATTTTTCTTACCAATTGTGAAT-3'(SEQ ID NO:1717)
5'-UUAUUUUUCUUACCAAUUGUGAAUG-3'(SEQ ID NO:5313)
3'-AGAAUAAAAAGAAUGGUUAACACUUAC-5'(SEQ ID NO:312)
KRAS-1161靶:5'-TCTTATTTTTCTTACCAATTGTGAATG-3'(SEQ ID NO:1718)
5'-UAUUUUUCUUACCAAUUGUGAAUGU-3'(SEQ ID NO:5314)
3'-GAAUAAAAAGAAUGGUUAACACUUACA-5'(SEQ ID NO:313)
KRAS-1162靶:5'-CTTATTTTTCTTACCAATTGTGAATGT-3'(SEQ ID NO:1719)
5'-GUUGGUGUGAAACAAAUUAAUGAAG-3'(SEQ ID NO:5315)
3'-UACAACCACACUUUGUUUAAUUACUUC-5'(SEQ ID NO:314)
KRAS-1185靶:5'-ATGTTGGTGTGAAACAAATTAATGAAG-3'(SEQ ID NO:1720)
5'-GGUGUGAAACAAAUUAAUGAAGCUU-3'(SEQ ID NO:5316)
3'-AACCACACUUUGUUUAAUUACUUCGAA-5'(SEQ ID NO:315)
KRAS-1188靶:5'-TTGGTGTGAAACAAATTAATGAAGCTT-3'(SEQ ID NO:1721)
5'-GUGUGAAACAAAUUAAUGAAGCUUU-3'(SEQ ID NO:5317)
3'-ACCACACUUUGUUUAAUUACUUCGAAA-5'(SEQ ID NO:316)
KRAS-1189靶:5'-TGGTGTGAAACAAATTAATGAAGCTTT-3'(SEQ ID NO:1722)
5'-CAAAUUAAUGAAGCUUUUGAAUCAU-3'(SEQ ID NO:5318)
3'-UUGUUUAAUUACUUCGAAAACUUAGUA-5'(SEQ ID NO:317)
KRAS-1197靶:5'-AACAAATTAATGAAGCTTTTGAATCAT-3'(SEQ ID NO:1723)
5'-AAAUUAAUGAAGCUUUUGAAUCAUC-3'(SEQ ID NO:5319)
3'-UGUUUAAUUACUUCGAAAACUUAGUAG-5'(SEQ ID NO:318)
KRAS-1198靶:5'-ACAAATTAATGAAGCTTTTGAATCATC-3'(SEQ ID NO:1724)
5'-UGUGUUUUAUCUAGUCACAUAAAUG-3'(SEQ ID NO:5320)
3'-AGACACAAAAUAGAUCAGUGUAUUUAC-5'(SEQ ID NO:319)
KRAS-1230靶:5'-TCTGTGTTTTATCTAGTCACATAAATG-3'(SEQ ID NO:1725)
5'-GUGUUUUAUCUAGUCACAUAAAUGG-3'(SEQ ID NO:5321)
3'-GACACAAAAUAGAUCAGUGUAUUUACC-5'(SEQ ID NO:320)
KRAS-1231靶:5'-CTGTGTTTTATCTAGTCACATAAATGG-3'(SEQ ID NO:1726)
5'-UUUUAUCUAGUCACAUAAAUGGAUU-3'(SEQ ID NO:5322)
3'-ACAAAAUAGAUCAGUGUAUUUACCUAA-5'(SEQ ID NO:321)
KRAS-1234靶:5'-TGTTTTATCTAGTCACATAAATGGATT-3'(SEQ ID NO:1727)
5'-UUUAUCUAGUCACAUAAAUGGAUUA-3'(SEQ ID NO:5323)
3'-CAAAAUAGAUCAGUGUAUUUACCUAAU-5'(SEQ ID NO:322)
KRAS-1235靶:5'-GTTTTATCTAGTCACATAAATGGATTA-3'(SEQ ID NO:1728)
5'-CUAGUCACAUAAAUGGAUUAAUUAC-3'(SEQ ID NO:5324)
3'-UAGAUCAGUGUAUUUACCUAAUUAAUG-5'(SEQ ID NO:323)
KRAS-1240靶:5'-ATCTAGTCACATAAATGGATTAATTAC-3'(SEQ ID NO:1729)
5'-UAGUCACAUAAAUGGAUUAAUUACU-3'(SEQ ID NO:5325)
3'-AGAUCAGUGUAUUUACCUAAUUAAUGA-5'(SEQ ID NO:324)
KRAS-1241靶:5'-TCTAGTCACATAAATGGATTAATTACT-3'(SEQ ID NO:1730)
5'-UAAAUGGAUUAAUUACUAAUUUCAG-3'(SEQ ID NO:5326)
3'-GUAUUUACCUAAUUAAUGAUUAAAGUC-5'(SEQ ID NO:325)
KRAS-1249靶:5'-CATAAATGGATTAATTACTAATTTCAG-3'(SEQ ID NO:1731)
5'-AAAUGGAUUAAUUACUAAUUUCAGU-3'(SEQ ID NO:5327)
3'-UAUUUACCUAAUUAAUGAUUAAAGUCA-5'(SEQ ID NO:326)
KRAS-1250靶:5'-ATAAATGGATTAATTACTAATTTCAGT-3'(SEQ ID NO:1732)
5'-GAUUAAUUACUAAUUUCAGUUGAGA-3'(SEQ ID NO:5328)
3'-ACCUAAUUAAUGAUUAAAGUCAACUCU-5'(SEQ ID NO:327)
KRAS-1255靶:5'-TGGATTAATTACTAATTTCAGTTGAGA-3'(SEQ ID NO:1733)
5'-UUAAUUACUAAUUUCAGUUGAGACC-3'(SEQ ID NO:5329)
3'-CUAAUUAAUGAUUAAAGUCAACUCUGG-5'(SEQ ID NO:328)
KRAS-1257靶:5'-GATTAATTACTAATTTCAGTTGAGACC-3'(SEQ ID NO:1734)
5'-UAAUUACUAAUUUCAGUUGAGACCU-3'(SEQ ID NO:5330)
3'-UAAUUAAUGAUUAAAGUCAACUCUGGA-5'(SEQ ID NO:329)
KRAS-1258靶:5'-ATTAATTACTAATTTCAGTTGAGACCT-3'(SEQ ID NO:1735)
5'-AAUUACUAAUUUCAGUUGAGACCUU-3'(SEQ ID NO:5331)
3'-AAUUAAUGAUUAAAGUCAACUCUGGAA-5'(SEQ ID NO:330)
KRAS-1259靶:5'-TTAATTACTAATTTCAGTTGAGACCTT-3'(SEQ ID NO:1736)
5'-AUUGGUUUUUACUGAAACAUUGAGG-3'(SEQ ID NO:5332)
3'-AUUAACCAAAAAUGACUUUGUAACUCC-5'(SEQ ID NO:331)
KRAS-1287靶:5'-TAATTGGTTTTTACTGAAACATTGAGG-3'(SEQ ID NO:1737)
5'-GUUUUUACUGAAACAUUGAGGGAAC-3'(SEQ ID NO:5333)
3'-ACCAAAAAUGACUUUGUAACUCCCUUG-5'(SEQ ID NO:332)
KRAS-1291靶:5'-TGGTTTTTACTGAAACATTGAGGGAAC-3'(SEQ ID NO:1738)
5'-UUUUUACUGAAACAUUGAGGGAACA-3'(SEQ ID NO:5334)
3'-CCAAAAAUGACUUUGUAACUCCCUUGU-5'(SEQ ID NO:333)
KRAS-1292靶:5'-GGTTTTTACTGAAACATTGAGGGAACA-3'(SEQ ID NO:1739)
5'-UGAGGGAACACAAAUUUAUGGGCUU-3'(SEQ ID NO:5335)
3'-UAACUCCCUUGUGUUUAAAUACCCGAA-5'(SEQ ID NO:334)
KRAS-1307靶:5'-ATTGAGGGAACACAAATTTATGGGCTT-3'(SEQ ID NO:1740)
5'-GAGGGAACACAAAUUUAUGGGCUUC-3'(SEQ ID NO:5336)
3'-AACUCCCUUGUGUUUAAAUACCCGAAG-5'(SEQ ID NO:335)
KRAS-1308靶:5'-TTGAGGGAACACAAATTTATGGGCTTC-3'(SEQ ID NO:1741)
5'-AUGAAUGUAAAGUUACACUGUUCAC-3'(SEQ ID NO:5337)
3'-ACUACUUACAUUUCAAUGUGACAAGUG-5'(SEQ ID NO:336)
KRAS-1381靶:5'-TGATGAATGTAAAGTTACACTGTTCAC-3'(SEQ ID NO:1742)
5'-UGAAUGUAAAGUUACACUGUUCACA-3'(SEQ ID NO:5338)
3'-CUACUUACAUUUCAAUGUGACAAGUGU-5'(SEQ ID NO:337)
KRAS-1382靶:5'-GATGAATGTAAAGTTACACTGTTCACA-3'(SEQ ID NO:1743)
5'-AAAAUAUUAUAUUUUUUCUAUAAAA-3'(SEQ ID NO:5339)
3'-GGUUUUAUAAUAUAAAAAAGAUAUUUU-5'(SEQ ID NO:338)
KRAS-1454靶:5'-CCAAAATATTATATTTTTTCTATAAAA-3'(SEQ ID NO:1744)
5'-AAAUAUUAUAUUUUUUCUAUAAAAA-3'(SEQ ID NO:5340)
3'-GUUUUAUAAUAUAAAAAAGAUAUUUUU-5'(SEQ ID NO:339)
KRAS-1455靶:5'-CAAAATATTATATTTTTTCTATAAAAA-3'(SEQ ID NO:1745)
5'-AAUAUUAUAUUUUUUCUAUAAAAAG-3'(SEQ ID NO:5341)
3'-UUUUAUAAUAUAAAAAAGAUAUUUUUC-5'(SEQ ID NO:340)
KRAS-1456靶:5'-AAAATATTATATTTTTTCTATAAAAAG-3'(SEQ ID NO:1746)
5'-AUAUUAUAUUUUUUCUAUAAAAAGA-3'(SEQ ID NO:5342)
3'-UUUAUAAUAUAAAAAAGAUAUUUUUCU-5'(SEQ ID NO:341)
KRAS-1457靶:5'-AAATATTATATTTTTTCTATAAAAAGA-3'(SEQ ID NO:1747)
5'-AUUAUAUUUUUUCUAUAAAAAGAAA-3'(SEQ ID NO:5343)
3'-UAUAAUAUAAAAAAGAUAUUUUUCUUU-5'(SEQ ID NO:342)
KRAS-1459靶:5'-ATATTATATTTTTTCTATAAAAAGAAA-3'(SEQ ID NO:1748)
5'-UUAUAUUUUUUCUAUAAAAAGAAAA-3'(SEQ ID NO:5344)
3'-AUAAUAUAAAAAAGAUAUUUUUCUUUU-5'(SEQ ID NO:343)
KRAS-1460靶:5'-TATTATATTTTTTCTATAAAAAGAAAA-3'(SEQ ID NO:1749)
5'-UAUAUUUUUUCUAUAAAAAGAAAAA-3'(SEQ ID NO:5345)
3'-UAAUAUAAAAAAGAUAUUUUUCUUUUU-5'(SEQ ID NO:344)
KRAS-1461靶:5'-ATTATATTTTTTCTATAAAAAGAAAAA-3'(SEQ ID NO:1750)
5'-AUAUUUUUUCUAUAAAAAGAAAAAA-3'(SEQ ID NO:5346)
3'-AAUAUAAAAAAGAUAUUUUUCUUUUUU-5'(SEQ ID NO:345)
KRAS-1462靶:5'-TTATATTTTTTCTATAAAAAGAAAAAA-3'(SEQ ID NO:1751)
5'-UAUUUUUUCUAUAAAAAGAAAAAAA-3'(SEQ ID NO:5347)
3'-AUAUAAAAAAGAUAUUUUUCUUUUUUU-5'(SEQ ID NO:346)
KRAS-1463靶:5'-TATATTTTTTCTATAAAAAGAAAAAAA-3'(SEQ ID NO:1752)
5'-AUUUUUUCUAUAAAAAGAAAAAAAU-3'(SEQ ID NO:5348)
3'-UAUAAAAAAGAUAUUUUUCUUUUUUUA-5'(SEQ ID NO:347)
KRAS-1464靶:5'-ATATTTTTTCTATAAAAAGAAAAAAAT-3'(SEQ ID NO:1753)
5'-UUUUUUCUAUAAAAAGAAAAAAAUG-3'(SEQ ID NO:5349)
3'-AUAAAAAAGAUAUUUUUCUUUUUUUAC-5'(SEQ ID NO:348)
KRAS-1465靶:5'-TATTTTTTCTATAAAAAGAAAAAAATG-3'(SEQ ID NO:1754)
5'-UUUUUCUAUAAAAAGAAAAAAAUGG-3'(SEQ ID NO:5350)
3'-UAAAAAAGAUAUUUUUCUUUUUUUACC-5'(SEQ ID NO:349)
KRAS-1466靶:5'-ATTTTTTCTATAAAAAGAAAAAAATGG-3'(SEQ ID NO:1755)
5'-CUAUAAAAAGAAAAAAAUGGAAAAA-3'(SEQ ID NO:5351)
3'-AAGAUAUUUUUCUUUUUUUACCUUUUU-5'(SEQ ID NO:350)
KRAS-1471靶:5'-TTCTATAAAAAGAAAAAAATGGAAAAA-3'(SEQ ID NO:1756)
5'-UAUAAAAAGAAAAAAAUGGAAAAAA-3'(SEQ ID NO:5352)
3'-AGAUAUUUUUCUUUUUUUACCUUUUUU-5'(SEQ ID NO:351)
KRAS-1472靶:5'-TCTATAAAAAGAAAAAAATGGAAAAAA-3'(SEQ ID NO:1757)
5'-UAAAAAGAAAAAAAUGGAAAAAAAU-3'(SEQ ID NO:5353)
3'-AUAUUUUUCUUUUUUUACCUUUUUUUA-5'(SEQ ID NO:352)
KRAS-1474靶:5'-TATAAAAAGAAAAAAATGGAAAAAAAT-3'(SEQ ID NO:1758)
5'-AAAAAGAAAAAAAUGGAAAAAAAUU-3'(SEQ ID NO:5354)
3'-UAUUUUUCUUUUUUUACCUUUUUUUAA-5'(SEQ ID NO:353)
KRAS-1475靶:5'-ATAAAAAGAAAAAAATGGAAAAAAATT-3'(SEQ ID NO:1759)
5'-AAAAGAAAAAAAUGGAAAAAAAUUA-3'(SEQ ID NO:5355)
3'-AUUUUUCUUUUUUUACCUUUUUUUAAU-5'(SEQ ID NO:354)
KRAS-1476靶:5'-TAAAAAGAAAAAAATGGAAAAAAATTA-3'(SEQ ID NO:1760)
5'-AAAGAAAAAAAUGGAAAAAAAUUAC-3'(SEQ ID NO:5356)
3'-UUUUUCUUUUUUUACCUUUUUUUAAUG-5'(SEQ ID NO:355)
KRAS-1477靶:5'-AAAAAGAAAAAAATGGAAAAAAATTAC-3'(SEQ ID NO:1761)
5'-AAGAAAAAAAUGGAAAAAAAUUACA-3'(SEQ ID NO:5357)
3'-UUUUCUUUUUUUACCUUUUUUUAAUGU-5'(SEQ ID NO:356)
KRAS-1478靶:5'-AAAAGAAAAAAATGGAAAAAAATTACA-3'(SEQ ID NO:1762)
5'-AGAAAAAAAUGGAAAAAAAUUACAA-3'(SEQ ID NO:5358)
3'-UUUCUUUUUUUACCUUUUUUUAAUGUU-5'(SEQ ID NO:357)
KRAS-1479靶:5'-AAAGAAAAAAATGGAAAAAAATTACAA-3'(SEQ ID NO:1763)
5'-GAAAAAAAUGGAAAAAAAUUACAAG-3'(SEQ ID NO:5359)
3'-UUCUUUUUUUACCUUUUUUUAAUGUUC-5'(SEQ ID NO:358)
KRAS-1480靶:5'-AAGAAAAAAATGGAAAAAAATTACAAG-3'(SEQ ID NO:1764)
5'-AAAAUGGAAAAAAAUUACAAGGCAA-3'(SEQ ID NO:5360)
3'-UUUUUUACCUUUUUUUAAUGUUCCGUU-5'(SEQ ID NO:359)
KRAS-1484靶:5'-AAAAAATGGAAAAAAATTACAAGGCAA-3'(SEQ ID NO:1765)
5'-AAAUGGAAAAAAAUUACAAGGCAAU-3'(SEQ ID NO:5361)
3'-UUUUUACCUUUUUUUAAUGUUCCGUUA-5'(SEQ ID NO:360)
KRAS-1485靶:5'-AAAAATGGAAAAAAATTACAAGGCAAT-3'(SEQ ID NO:1766)
5'-GAAAAAAAUUACAAGGCAAUGGAAA-3'(SEQ ID NO:5362)
3'-ACCUUUUUUUAAUGUUCCGUUACCUUU-5'(SEQ ID NO:361)
KRAS-1490靶:5'-TGGAAAAAAATTACAAGGCAATGGAAA-3'(SEQ ID NO:1767)
5'-AAAAAAAUUACAAGGCAAUGGAAAC-3'(SEQ ID NO:5363)
3'-CCUUUUUUUAAUGUUCCGUUACCUUUG-5'(SEQ ID NO:362)
KRAS-1491靶:5'-GGAAAAAAATTACAAGGCAATGGAAAC-3'(SEQ ID NO:1768)
5'-AAAAAAUUACAAGGCAAUGGAAACU-3'(SEQ ID NO:5364)
3'-CUUUUUUUAAUGUUCCGUUACCUUUGA-5'(SEQ ID NO:363)
KRAS-1492靶:5'-GAAAAAAATTACAAGGCAATGGAAACT-3'(SEQ ID NO:1769)
5'-CAUUUCCUUUUCACAUUAGAUAAAU-3'(SEQ ID NO:5365)
3'-CGGUAAAGGAAAAGUGUAAUCUAUUUA-5'(SEQ ID NO:364)
KRAS-1527靶:5'-GCCATTTCCTTTTCACATTAGATAAAT-3'(SEQ ID NO:1770)
5'-CUUUUCACAUUAGAUAAAUUACUAU-3'(SEQ ID NO:5366)
3'-AGGAAAAGUGUAAUCUAUUUAAUGAUA-5'(SEQ ID NO:365)
KRAS-1533靶:5'-TCCTTTTCACATTAGATAAATTACTAT-3'(SEQ ID NO:1771)
5'-CAUUAGAUAAAUUACUAUAAAGACU-3'(SEQ ID NO:5367)
3'-GUGUAAUCUAUUUAAUGAUAUUUCUGA-5'(SEQ ID NO:366)
KRAS-1540靶:5'-CACATTAGATAAATTACTATAAAGACT-3'(SEQ ID NO:1772)
5'-AUUAGAUAAAUUACUAUAAAGACUC-3'(SEQ ID NO:5368)
3'-UGUAAUCUAUUUAAUGAUAUUUCUGAG-5'(SEQ ID NO:367)
KRAS-1541靶:5'-ACATTAGATAAATTACTATAAAGACTC-3'(SEQ ID NO:1773)
5'-UUAGAUAAAUUACUAUAAAGACUCC-3'(SEQ ID NO:5369)
3'-GUAAUCUAUUUAAUGAUAUUUCUGAGG-5'(SEQ ID NO:368)
KRAS-1542靶:5'-CATTAGATAAATTACTATAAAGACTCC-3'(SEQ ID NO:1774)
5'-UAUGAAAUGGGGAUUAUUAUAGCAA-3'(SEQ ID NO:5370)
3'-UCAUACUUUACCCCUAAUAAUAUCGUU-5'(SEQ ID NO:369)
KRAS-1597靶:5'-AGTATGAAATGGGGATTATTATAGCAA-3'(SEQ ID NO:1775)
5'-GGGAUUAUUAUAGCAACCAUUUUGG-3'(SEQ ID NO:5371)
3'-ACCCCUAAUAAUAUCGUUGGUAAAACC-5'(SEQ ID NO:370)
KRAS-1606靶:5'-TGGGGATTATTATAGCAACCATTTTGG-3'(SEQ ID NO:1776)
5'-CUAUAUUUACAUGCUACUAAAUUUU-3'(SEQ ID NO:5372)
3'-CCGAUAUAAAUGUACGAUGAUUUAAAA-5'(SEQ ID NO:371)
KRAS-1633靶:5'-GGCTATATTTACATGCTACTAAATTTT-3'(SEQ ID NO:1777)
5'-UAUAUUUACAUGCUACUAAAUUUUU-3'(SEQ ID NO:5373)
3'-CGAUAUAAAUGUACGAUGAUUUAAAAA-5'(SEQ ID NO:372)
KRAS-1634靶:5'-GCTATATTTACATGCTACTAAATTTTT-3'(SEQ ID NO:1778)
5'-AUAUUUACAUGCUACUAAAUUUUUA-3'(SEQ ID NO:5374)
3'-GAUAUAAAUGUACGAUGAUUUAAAAAU-5'(SEQ ID NO:373)
KRAS-1635靶:5'-CTATATTTACATGCTACTAAATTTTTA-3'(SEQ ID NO:1779)
5'-UAUUUACAUGCUACUAAAUUUUUAU-3'(SEQ ID NO:5375)
3'-AUAUAAAUGUACGAUGAUUUAAAAAUA-5'(SEQ ID NO:374)
KRAS-1636靶:5'-TATATTTACATGCTACTAAATTTTTAT-3'(SEQ ID NO:1780)
5'-AUUUACAUGCUACUAAAUUUUUAUA-3'(SEQ ID NO:5376)
3'-UAUAAAUGUACGAUGAUUUAAAAAUAU-5'(SEQ ID NO:375)
KRAS-1637靶:5'-ATATTTACATGCTACTAAATTTTTATA-3'(SEQ ID NO:1781)
5'-CAUGCUACUAAAUUUUUAUAAUAAU-3'(SEQ ID NO:5377)
3'-AUGUACGAUGAUUUAAAAAUAUUAUUA-5'(SEQ ID NO:376)
KRAS-1642靶:5'-TACATGCTACTAAATTTTTATAATAAT-3'(SEQ ID NO:1782)
5'-CUAAAUUUUUAUAAUAAUUGAAAAG-3'(SEQ ID NO:5378)
3'-AUGAUUUAAAAAUAUUAUUAACUUUUC-5'(SEQ ID NO:377)
KRAS-1649靶:5'-TACTAAATTTTTATAATAATTGAAAAG-3'(SEQ ID NO:1783)
5'-UAAAUUUUUAUAAUAAUUGAAAAGA-3'(SEQ ID NO:5379)
3'-UGAUUUAAAAAUAUUAUUAACUUUUCU-5'(SEQ ID NO:378)
KRAS-1650靶:5'-ACTAAATTTTTATAATAATTGAAAAGA-3'(SEQ ID NO:1784)
5'-AAUUUUUAUAAUAAUUGAAAAGAUU-3'(SEQ ID NO:5380)
3'-AUUUAAAAAUAUUAUUAACUUUUCUAA-5'(SEQ ID NO:379)
KRAS-1652靶:5'-TAAATTTTTATAATAATTGAAAAGATT-3'(SEQ ID NO:1785)
5'-AUUUUUAUAAUAAUUGAAAAGAUUU-3'(SEQ ID NO:5381)
3'-UUUAAAAAUAUUAUUAACUUUUCUAAA-5'(SEQ ID NO:380)
KRAS-1653靶:5'-AAATTTTTATAATAATTGAAAAGATTT-3'(SEQ ID NO:1786)
5'-UUUUUAUAAUAAUUGAAAAGAUUUU-3'(SEQ ID NO:5382)
3'-UUAAAAAUAUUAUUAACUUUUCUAAAA-5'(SEQ ID NO:381)
KRAS-1654靶:5'-AATTTTTATAATAATTGAAAAGATTTT-3'(SEQ ID NO:1787)
5'-UUUUAUAAUAAUUGAAAAGAUUUUA-3'(SEQ ID NO:5383)
3'-UAAAAAUAUUAUUAACUUUUCUAAAAU-5'(SEQ ID NO:382)
KRAS-1655靶:5'-ATTTTTATAATAATTGAAAAGATTTTA-3'(SEQ ID NO:1788)
5'-UUUAUAAUAAUUGAAAAGAUUUUAA-3'(SEQ ID NO:5384)
3'-AAAAAUAUUAUUAACUUUUCUAAAAUU-5'(SEQ ID NO:383)
KRAS-1656靶:5'-TTTTTATAATAATTGAAAAGATTTTAA-3'(SEQ ID NO:1789)
5'-UUAUAAUAAUUGAAAAGAUUUUAAC-3'(SEQ ID NO:5385)
3'-AAAAUAUUAUUAACUUUUCUAAAAUUG-5'(SEQ ID NO:384)
KRAS-1657靶:5'-TTTTATAATAATTGAAAAGATTTTAAC-3'(SEQ ID NO:1790)
5'-UAUAAUAAUUGAAAAGAUUUUAACA-3'(SEQ ID NO:5386)
3'-AAAUAUUAUUAACUUUUCUAAAAUUGU-5'(SEQ ID NO:385)
KRAS-1658靶:5'-TTTATAATAATTGAAAAGATTTTAACA-3'(SEQ ID NO:1791)
5'-AUAAUAAUUGAAAAGAUUUUAACAA-3'(SEQ ID NO:5387)
3'-AAUAUUAUUAACUUUUCUAAAAUUGUU-5'(SEQ ID NO:386)
KRAS-1659靶:5'-TTATAATAATTGAAAAGATTTTAACAA-3'(SEQ ID NO:1792)
5'-UAAUAAUUGAAAAGAUUUUAACAAG-3'(SEQ ID NO:5388)
3'-AUAUUAUUAACUUUUCUAAAAUUGUUC-5'(SEQ ID NO:387)
KRAS-1660靶:5'-TATAATAATTGAAAAGATTTTAACAAG-3'(SEQ ID NO:1793)
5'-AAUUGAAAAGAUUUUAACAAGUAUA-3'(SEQ ID NO:5389)
3'-UAUUAACUUUUCUAAAAUUGUUCAUAU-5'(SEQ ID NO:388)
KRAS-1664靶:5'-ATAATTGAAAAGATTTTAACAAGTATA-3'(SEQ ID NO:1794)
5'-AUUGAAAAGAUUUUAACAAGUAUAA-3'(SEQ ID NO:5390)
3'-AUUAACUUUUCUAAAAUUGUUCAUAUU-5'(SEQ ID NO:389)
KRAS-1665靶:5'-TAATTGAAAAGATTTTAACAAGTATAA-3'(SEQ ID NO:1795)
5'-UGAAAAGAUUUUAACAAGUAUAAAA-3'(SEQ ID NO:5391)
3'-UAACUUUUCUAAAAUUGUUCAUAUUUU-5'(SEQ ID NO:390)
KRAS-1667靶:5'-ATTGAAAAGATTTTAACAAGTATAAAA-3'(SEQ ID NO:1796)
5'-GAAAAGAUUUUAACAAGUAUAAAAA-3'(SEQ ID NO:5392)
3'-AACUUUUCUAAAAUUGUUCAUAUUUUU-5'(SEQ ID NO:391)
KRAS-1668靶:5'-TTGAAAAGATTTTAACAAGTATAAAAA-3'(SEQ ID NO:1797)
5'-AAAAGAUUUUAACAAGUAUAAAAAA-3'(SEQ ID NO:5393)
3'-ACUUUUCUAAAAUUGUUCAUAUUUUUU-5'(SEQ ID NO:392)
KRAS-1669靶:5'-TGAAAAGATTTTAACAAGTATAAAAAA-3'(SEQ ID NO:1798)
5'-AAAGAUUUUAACAAGUAUAAAAAAU-3'(SEQ ID NO:5394)
3'-CUUUUCUAAAAUUGUUCAUAUUUUUUA-5'(SEQ ID NO:393)
KRAS-1670靶:5'-GAAAAGATTTTAACAAGTATAAAAAAT-3'(SEQ ID NO:1799)
5'-AAGAUUUUAACAAGUAUAAAAAAUU-3'(SEQ ID NO:5395)
3'-UUUUCUAAAAUUGUUCAUAUUUUUUAA-5'(SEQ ID NO:394)
KRAS-1671靶:5'-AAAAGATTTTAACAAGTATAAAAAATT-3'(SEQ ID NO:1800)
5'-AGAUUUUAACAAGUAUAAAAAAUUC-3'(SEQ ID NO:5396)
3'-UUUCUAAAAUUGUUCAUAUUUUUUAAG-5'(SEQ ID NO:395)
KRAS-1672靶:5'-AAAGATTTTAACAAGTATAAAAAATTC-3'(SEQ ID NO:1801)
5'-GAUUUUAACAAGUAUAAAAAAUUCU-3'(SEQ ID NO:5397)
3'-UUCUAAAAUUGUUCAUAUUUUUUAAGA-5'(SEQ ID NO:396)
KRAS-1673靶:5'-AAGATTTTAACAAGTATAAAAAATTCT-3'(SEQ ID NO:1802)
5'-AUUUUAACAAGUAUAAAAAAUUCUC-3'(SEQ ID NO:5398)
3'-UCUAAAAUUGUUCAUAUUUUUUAAGAG-5'(SEQ ID NO:397)
KRAS-1674靶:5'-AGATTTTAACAAGTATAAAAAATTCTC-3'(SEQ ID NO:1803)
5'-UUUUAACAAGUAUAAAAAAUUCUCA-3'(SEQ ID NO:5399)
3'-CUAAAAUUGUUCAUAUUUUUUAAGAGU-5'(SEQ ID NO:398)
KRAS-1675靶:5'-GATTTTAACAAGTATAAAAAATTCTCA-3'(SEQ ID NO:1804)
5'-AAGUAUAAAAAAUUCUCAUAGGAAU-3'(SEQ ID NO:5400)
3'-UGUUCAUAUUUUUUAAGAGUAUCCUUA-5'(SEQ ID NO:399)
KRAS-1682靶:5'-ACAAGTATAAAAAATTCTCATAGGAAT-3'(SEQ ID NO:1805)
5'-AGUAUAAAAAAUUCUCAUAGGAAUU-3'(SEQ ID NO:5401)
3'-GUUCAUAUUUUUUAAGAGUAUCCUUAA-5'(SEQ ID NO:400)
KRAS-1683靶:5'-CAAGTATAAAAAATTCTCATAGGAATT-3'(SEQ ID NO:1806)
5'-GUAUAAAAAAUUCUCAUAGGAAUUA-3'(SEQ ID NO:5402)
3'-UUCAUAUUUUUUAAGAGUAUCCUUAAU-5'(SEQ ID NO:401)
KRAS-1684靶:5'-AAGTATAAAAAATTCTCATAGGAATTA-3'(SEQ ID NO:1807)
5'-UAUAAAAAAUUCUCAUAGGAAUUAA-3'(SEQ ID NO:5403)
3'-UCAUAUUUUUUAAGAGUAUCCUUAAUU-5'(SEQ ID NO:402)
KRAS-1685靶:5'-AGTATAAAAAATTCTCATAGGAATTAA-3'(SEQ ID NO:1808)
5'-AUAAAAAAUUCUCAUAGGAAUUAAA-3'(SEQ ID NO:5404)
3'-CAUAUUUUUUAAGAGUAUCCUUAAUUU-5'(SEQ ID NO:403)
KRAS-1686靶:5'-GTATAAAAAATTCTCATAGGAATTAAA-3'(SEQ ID NO:1809)
5'-UAAAAAAUUCUCAUAGGAAUUAAAU-3'(SEQ ID NO:5405)
3'-AUAUUUUUUAAGAGUAUCCUUAAUUUA-5'(SEQ ID NO:404)
KRAS-1687靶:5'-TATAAAAAATTCTCATAGGAATTAAAT-3'(SEQ ID NO:1810)
5'-AAAAAAUUCUCAUAGGAAUUAAAUG-3'(SEQ ID NO:5406)
3'-UAUUUUUUAAGAGUAUCCUUAAUUUAC-5'(SEQ ID NO:405)
KRAS-1688靶:5'-ATAAAAAATTCTCATAGGAATTAAATG-3'(SEQ ID NO:1811)
5'-AAAAAUUCUCAUAGGAAUUAAAUGU-3'(SEQ ID NO:5407)
3'-AUUUUUUAAGAGUAUCCUUAAUUUACA-5'(SEQ ID NO:406)
KRAS-1689靶:5'-TAAAAAATTCTCATAGGAATTAAATGT-3'(SEQ ID NO:1812)
5'-AAAUUCUCAUAGGAAUUAAAUGUAG-3'(SEQ ID NO:5408)
3'-UUUUUAAGAGUAUCCUUAAUUUACAUC-5'(SEQ ID NO:407)
KRAS-1691靶:5'-AAAAATTCTCATAGGAATTAAATGTAG-3'(SEQ ID NO:1813)
5'-AAUUCUCAUAGGAAUUAAAUGUAGU-3'(SEQ ID NO:5409)
3'-UUUUAAGAGUAUCCUUAAUUUACAUCA-5'(SEQ ID NO:408)
KRAS-1692靶:5'-AAAATTCTCATAGGAATTAAATGTAGT-3'(SEQ ID NO:1814)
5'-CUUUCAUAGUAUAACUUUAAAUCUU-3'(SEQ ID NO:5410)
3'-GAGAAAGUAUCAUAUUGAAAUUUAGAA-5'(SEQ ID NO:409)
KRAS-1736靶:5'-CTCTTTCATAGTATAACTTTAAATCTT-3'(SEQ ID NO:1815)
5'-AUAGUAUAACUUUAAAUCUUUUCUU-3'(SEQ ID NO:5411)
3'-AGUAUCAUAUUGAAAUUUAGAAAAGAA-5'(SEQ ID NO:410)
KRAS-1741靶:5'-TCATAGTATAACTTTAAATCTTTTCTT-3'(SEQ ID NO:1816)
5'-UAGUAUAACUUUAAAUCUUUUCUUC-3'(SEQ ID NO:5412)
3'-GUAUCAUAUUGAAAUUUAGAAAAGAAG-5'(SEQ ID NO:411)
KRAS-1742靶:5'-CATAGTATAACTTTAAATCTTTTCTTC-3'(SEQ ID NO:1817)
5'-UAAAUCUUUUCUUCAACUUGAGUCU-3'(SEQ ID NO:5413)
3'-AAAUUUAGAAAAGAAGUUGAACUCAGA-5'(SEQ ID NO:412)
KRAS-1753靶:5'-TTTAAATCTTTTCTTCAACTTGAGTCT-3'(SEQ ID NO:1818)
5'-AAAUCUUUUCUUCAACUUGAGUCUU-3'(SEQ ID NO:5414)
3'-AAUUUAGAAAAGAAGUUGAACUCAGAA-5'(SEQ ID NO:413)
KRAS-1754靶:5'-TTAAATCTTTTCTTCAACTTGAGTCTT-3'(SEQ ID NO:1819)
5'-CUUGAGUCUUUGAAGAUAGUUUUAA-3'(SEQ ID NO:5415)
3'-UUGAACUCAGAAACUUCUAUCAAAAUU-5'(SEQ ID NO:414)
KRAS-1769靶:5'-AACTTGAGTCTTTGAAGATAGTTTTAA-3'(SEQ ID NO:1820)
5'-UGAGUCUUUGAAGAUAGUUUUAAUU-3'(SEQ ID NO:5416)
3'-GAACUCAGAAACUUCUAUCAAAAUUAA-5'(SEQ ID NO:415)
KRAS-1771靶:5'-CTTGAGTCTTTGAAGATAGTTTTAATT-3'(SEQ ID NO:1821)
5'-GAGUCUUUGAAGAUAGUUUUAAUUC-3'(SEQ ID NO:5417)
3'-AACUCAGAAACUUCUAUCAAAAUUAAG-5'(SEQ ID NO:416)
KRAS-1772靶:5'-TTGAGTCTTTGAAGATAGTTTTAATTC-3'(SEQ ID NO:1822)
5'-GAUAGUUUUAAUUCUGCUUGUGACA-3'(SEQ ID NO:5418)
3'-UUCUAUCAAAAUUAAGACGAACACUGU-5'(SEQ ID NO:417)
KRAS-1783靶:5'-AAGATAGTTTTAATTCTGCTTGTGACA-3'(SEQ ID NO:1823)
5'-AUAGUUUUAAUUCUGCUUGUGACAU-3'(SEQ ID NO:5419)
3'-UCUAUCAAAAUUAAGACGAACACUGUA-5'(SEQ ID NO:418)
KRAS-1784靶:5'-AGATAGTTTTAATTCTGCTTGTGACAT-3'(SEQ ID NO:1824)
5'-UAGUUUUAAUUCUGCUUGUGACAUU-3'(SEQ ID NO:5420)
3'-CUAUCAAAAUUAAGACGAACACUGUAA-5'(SEQ ID NO:419)
KRAS-1785靶:5'-GATAGTTTTAATTCTGCTTGTGACATT-3'(SEQ ID NO:1825)
5'-CUUGUGACAUUAAAAGAUUAUUUGG-3'(SEQ ID NO:5421)
3'-ACGAACACUGUAAUUUUCUAAUAAACC-5'(SEQ ID NO:420)
KRAS-1799靶:5'-TGCTTGTGACATTAAAAGATTATTTGG-3'(SEQ ID NO:1826)
5'-CAUUGCUUUUGUUUCUUAAGAAAAC-3'(SEQ ID NO:5422)
3'-UCGUAACGAAAACAAAGAAUUCUUUUG-5'(SEQ ID NO:421)
KRAS-2047靶:5'-AGCATTGCTTTTGTTTCTTAAGAAAAC-3'(SEQ ID NO:1827)
5'-AUUGCUUUUGUUUCUUAAGAAAACA-3'(SEQ ID NO:5423)
3'-CGUAACGAAAACAAAGAAUUCUUUUGU-5'(SEQ ID NO:422)
KRAS-2048靶:5'-GCATTGCTTTTGTTTCTTAAGAAAACA-3'(SEQ ID NO:1828)
5'-UUUGUUUCUUAAGAAAACAAACUCU-3'(SEQ ID NO:5424)
3'-GAAAACAAAGAAUUCUUUUGUUUGAGA-5'(SEQ ID NO:423)
KRAS-2054靶:5'-CTTTTGTTTCTTAAGAAAACAAACTCT-3'(SEQ ID NO:1829)
5'-CUUAAGAAAACAAACUCUUUUUUAA-3'(SEQ ID NO:5425)
3'-AAGAAUUCUUUUGUUUGAGAAAAAAUU-5'(SEQ ID NO:424)
KRAS-2061靶:5'-TTCTTAAGAAAACAAACTCTTTTTTAA-3'(SEQ ID NO:1830)
5'-UUAAGAAAACAAACUCUUUUUUAAA-3'(SEQ ID NO:5426)
3'-AGAAUUCUUUUGUUUGAGAAAAAAUUU-5'(SEQ ID NO:425)
KRAS-2062靶:5'-TCTTAAGAAAACAAACTCTTTTTTAAA-3'(SEQ ID NO:1831)
5'-UAAGAAAACAAACUCUUUUUUAAAA-3'(SEQ ID NO:5427)
3'-GAAUUCUUUUGUUUGAGAAAAAAUUUU-5'(SEQ ID NO:426)
KRAS-2063靶:5'-CTTAAGAAAACAAACTCTTTTTTAAAA-3'(SEQ ID NO:1832)
5'-AAGAAAACAAACUCUUUUUUAAAAA-3'(SEQ ID NO:5428)
3'-AAUUCUUUUGUUUGAGAAAAAAUUUUU-5'(SEQ ID NO:427)
KRAS-2064靶:5'-TTAAGAAAACAAACTCTTTTTTAAAAA-3'(SEQ ID NO:1833)
5'-AGAAAACAAACUCUUUUUUAAAAAU-3'(SEQ ID NO:5429)
3'-AUUCUUUUGUUUGAGAAAAAAUUUUUA-5'(SEQ ID NO:428)
KRAS-2065靶:5'-TAAGAAAACAAACTCTTTTTTAAAAAT-3'(SEQ ID NO:1834)
5'-GAAAACAAACUCUUUUUUAAAAAUU-3'(SEQ ID NO:5430)
3'-UUCUUUUGUUUGAGAAAAAAUUUUUAA-5'(SEQ ID NO:429)
KRAS-2066靶:5'-AAGAAAACAAACTCTTTTTTAAAAATT-3'(SEQ ID NO:1835)
5'-AAAACAAACUCUUUUUUAAAAAUUA-3'(SEQ ID NO:5431)
3'-UCUUUUGUUUGAGAAAAAAUUUUUAAU-5'(SEQ ID NO:430)
KRAS-2067靶:5'-AGAAAACAAACTCTTTTTTAAAAATTA-3'(SEQ ID NO:1836)
5'-CAAACUCUUUUUUAAAAAUUACUUU-3'(SEQ ID NO:5432)
3'-UUGUUUGAGAAAAAAUUUUUAAUGAAA-5'(SEQ ID NO:431)
KRAS-2071靶:5'-AACAAACTCTTTTTTAAAAATTACTTT-3'(SEQ ID NO:1837)
5'-CUUUUUUAAAAAUUACUUUUAAAUA-3'(SEQ ID NO:5433)
3'-GAGAAAAAAUUUUUAAUGAAAAUUUAU-5'(SEQ ID NO:432)
KRAS-2077靶:5'-CTCTTTTTTAAAAATTACTTTTAAATA-3'(SEQ ID NO:1838)
5'-UUUUUUAAAAAUUACUUUUAAAUAU-3'(SEQ ID NO:5434)
3'-AGAAAAAAUUUUUAAUGAAAAUUUAUA-5'(SEQ ID NO:433)
KRAS-2078靶:5'-TCTTTTTTAAAAATTACTTTTAAATAT-3'(SEQ ID NO:1839)
5'-UUUUUAAAAAUUACUUUUAAAUAUU-3'(SEQ ID NO:5435)
3'-GAAAAAAUUUUUAAUGAAAAUUUAUAA-5'(SEQ ID NO:434)
KRAS-2079靶:5'-CTTTTTTAAAAATTACTTTTAAATATT-3'(SEQ ID NO:1840)
5'-UUUUAAAAAUUACUUUUAAAUAUUA-3'(SEQ ID NO:5436)
3'-AAAAAAUUUUUAAUGAAAAUUUAUAAU-5'(SEQ ID NO:435)
KRAS-2080靶:5'-TTTTTTAAAAATTACTTTTAAATATTA-3'(SEQ ID NO:1841)
5'-UUUAAAAAUUACUUUUAAAUAUUAA-3'(SEQ ID NO:5437)
3'-AAAAAUUUUUAAUGAAAAUUUAUAAUU-5'(SEQ ID NO:436)
KRAS-2081靶:5'-TTTTTAAAAATTACTTTTAAATATTAA-3'(SEQ ID NO:1842)
5'-UUAAAAAUUACUUUUAAAUAUUAAC-3'(SEQ ID NO:5438)
3'-AAAAUUUUUAAUGAAAAUUUAUAAUUG-5'(SEQ ID NO:437)
KRAS-2082靶:5'-TTTTAAAAATTACTTTTAAATATTAAC-3'(SEQ ID NO:1843)
5'-UAAAAAUUACUUUUAAAUAUUAACU-3'(SEQ ID NO:5439)
3'-AAAUUUUUAAUGAAAAUUUAUAAUUGA-5'(SEQ ID NO:438)
KRAS-2083靶:5'-TTTAAAAATTACTTTTAAATATTAACT-3'(SEQ ID NO:1844)
5'-AAAAAUUACUUUUAAAUAUUAACUC-3'(SEQ ID NO:5440)
3'-AAUUUUUAAUGAAAAUUUAUAAUUGAG-5'(SEQ ID NO:439)
KRAS-2084靶:5'-TTAAAAATTACTTTTAAATATTAACTC-3'(SEQ ID NO:1845)
5'-AAAAUUACUUUUAAAUAUUAACUCA-3'(SEQ ID NO:5441)
3'-AUUUUUAAUGAAAAUUUAUAAUUGAGU-5'(SEQ ID NO:440)
KRAS-2085靶:5'-TAAAAATTACTTTTAAATATTAACTCA-3'(SEQ ID NO:1846)
5'-CUUUUAAAUAUUAACUCAAAAGUUG-3'(SEQ ID NO:5442)
3'-AUGAAAAUUUAUAAUUGAGUUUUCAAC-5'(SEQ ID NO:441)
KRAS-2092靶:5'-TACTTTTAAATATTAACTCAAAAGTTG-3'(SEQ ID NO:1847)
5'-UUUUAAAUAUUAACUCAAAAGUUGA-3'(SEQ ID NO:5443)
3'-UGAAAAUUUAUAAUUGAGUUUUCAACU-5'(SEQ ID NO:442)
KRAS-2093靶:5'-ACTTTTAAATATTAACTCAAAAGTTGA-3'(SEQ ID NO:1848)
5'-UUAAAUAUUAACUCAAAAGUUGAGA-3'(SEQ ID NO:5444)
3'-AAAAUUUAUAAUUGAGUUUUCAACUCU-5'(SEQ ID NO:443)
KRAS-2095靶:5'-TTTTAAATATTAACTCAAAAGTTGAGA-3'(SEQ ID NO:1849)
5'-AAAUAUUAACUCAAAAGUUGAGAUU-3'(SEQ ID NO:5445)
3'-AAUUUAUAAUUGAGUUUUCAACUCUAA-5'(SEQ ID NO:444)
KRAS-2097靶:5'-TTAAATATTAACTCAAAAGTTGAGATT-3'(SEQ ID NO:1850)
5'-AAUAUUAACUCAAAAGUUGAGAUUU-3'(SEQ ID NO:5446)
3'-AUUUAUAAUUGAGUUUUCAACUCUAAA-5'(SEQ ID NO:445)
KRAS-2098靶:5'-TAAATATTAACTCAAAAGTTGAGATTT-3'(SEQ ID NO:1851)
5'-AUAUUAACUCAAAAGUUGAGAUUUU-3'(SEQ ID NO:5447)
3'-UUUAUAAUUGAGUUUUCAACUCUAAAA-5'(SEQ ID NO:446)
KRAS-2099靶:5'-AAATATTAACTCAAAAGTTGAGATTTT-3'(SEQ ID NO:1852)
5'-UAUUAACUCAAAAGUUGAGAUUUUG-3'(SEQ ID NO:5448)
3'-UUAUAAUUGAGUUUUCAACUCUAAAAC-5'(SEQ ID NO:447)
KRAS-2100靶:5'-AATATTAACTCAAAAGTTGAGATTTTG-3'(SEQ ID NO:1853)
5'-UGUGCCAAGACAUUAAUUUUUUUUU-3'(SEQ ID NO:5449)
3'-CCACACGGUUCUGUAAUUAAAAAAAAA-5'(SEQ ID NO:448)
KRAS-2134靶:5'-GGTGTGCCAAGACATTAATTTTTTTTT-3'(SEQ ID NO:1854)
5'-CAAGACAUUAAUUUUUUUUUUAAAC-3'(SEQ ID NO:5450)
3'-CGGUUCUGUAAUUAAAAAAAAAAUUUG-5'(SEQ ID NO:449)
KRAS-2139靶:5'-GCCAAGACATTAATTTTTTTTTTAAAC-3'(SEQ ID NO:1855)
5'-AAGACAUUAAUUUUUUUUUUAAACA-3'(SEQ ID NO:5451)
3'-GGUUCUGUAAUUAAAAAAAAAAUUUGU-5'(SEQ ID NO:450)
KRAS-2140靶:5'-CCAAGACATTAATTTTTTTTTTAAACA-3'(SEQ ID NO:1856)
5'-UUAAUUUUUUUUUUAAACAAUGAAG-3'(SEQ ID NO:5452)
3'-GUAAUUAAAAAAAAAAUUUGUUACUUC-5'(SEQ ID NO:451)
KRAS-2146靶:5'-CATTAATTTTTTTTTTAAACAATGAAG-3'(SEQ ID NO:1857)
5'-UAAUUUUUUUUUUAAACAAUGAAGU-3'(SEQ ID NO:5453)
3'-UAAUUAAAAAAAAAAUUUGUUACUUCA-5'(SEQ ID NO:452)
KRAS-2147靶:5'-ATTAATTTTTTTTTTAAACAATGAAGT-3'(SEQ ID NO:1858)
5'-AUUUUUUUUUUAAACAAUGAAGUGA-3'(SEQ ID NO:5454)
3'-AUUAAAAAAAAAAUUUGUUACUUCACU-5'(SEQ ID NO:453)
KRAS-2149靶:5'-TAATTTTTTTTTTAAACAATGAAGTGA-3'(SEQ ID NO:1859)
5'-UUUUUUUUUAAACAAUGAAGUGAAA-3'(SEQ ID NO:5455)
3'-UAAAAAAAAAAUUUGUUACUUCACUUU-5'(SEQ ID NO:454)
KRAS-2151靶:5'-ATTTTTTTTTTAAACAATGAAGTGAAA-3'(SEQ ID NO:1860)
5'-UUUUUUUUAAACAAUGAAGUGAAAA-3'(SEQ ID NO:5456)
3'-AAAAAAAAAAUUUGUUACUUCACUUUU-5'(SEQ ID NO:455)
KRAS-2152靶:5'-TTTTTTTTTTAAACAATGAAGTGAAAA-3'(SEQ ID NO:1861)
5'-UUUUUUUAAACAAUGAAGUGAAAAA-3'(SEQ ID NO:5457)
3'-AAAAAAAAAUUUGUUACUUCACUUUUU-5'(SEQ ID NO:456)
KRAS-2153靶:5'-TTTTTTTTTAAACAATGAAGTGAAAAA-3'(SEQ ID NO:1862)
5'-UUUUUUAAACAAUGAAGUGAAAAAG-3'(SEQ ID NO:5458)
3'-AAAAAAAAUUUGUUACUUCACUUUUUC-5'(SEQ ID NO:457)
KRAS-2154靶:5'-TTTTTTTTAAACAATGAAGTGAAAAAG-3'(SEQ ID NO:1863)
5'-UUUUUAAACAAUGAAGUGAAAAAGU-3'(SEQ ID NO:5459)
3'-AAAAAAAUUUGUUACUUCACUUUUUCA-5'(SEQ ID NO:458)
KRAS-2155靶:5'-TTTTTTTAAACAATGAAGTGAAAAAGT-3'(SEQ ID NO:1864)
5'-UUUAAACAAUGAAGUGAAAAAGUUU-3'(SEQ ID NO:5460)
3'-AAAAAUUUGUUACUUCACUUUUUCAAA-5'(SEQ ID NO:459)
KRAS-2157靶:5'-TTTTTAAACAATGAAGTGAAAAAGTTT-3'(SEQ ID NO:1865)
5'-UUAAACAAUGAAGUGAAAAAGUUUU-3'(SEQ ID NO:5461)
3'-AAAAUUUGUUACUUCACUUUUUCAAAA-5'(SEQ ID NO:460)
KRAS-2158靶:5'-TTTTAAACAATGAAGTGAAAAAGTTTT-3'(SEQ ID NO:1866)
5'-UAAACAAUGAAGUGAAAAAGUUUUA-3'(SEQ ID NO:5462)
3'-AAAUUUGUUACUUCACUUUUUCAAAAU-5'(SEQ ID NO:461)
KRAS-2159靶:5'-TTTAAACAATGAAGTGAAAAAGTTTTA-3'(SEQ ID NO:1867)
5'-GAAGUGAAAAAGUUUUACAAUCUCU-3'(SEQ ID NO:5463)
3'-UACUUCACUUUUUCAAAAUGUUAGAGA-5'(SEQ ID NO:462)
KRAS-2167靶:5'-ATGAAGTGAAAAAGTTTTACAATCTCT-3'(SEQ ID NO:1868)
5'-AAAAAGUUUUACAAUCUCUAGGUUU-3'(SEQ ID NO:5464)
3'-ACUUUUUCAAAAUGUUAGAGAUCCAAA-5'(SEQ ID NO:463)
KRAS-2173靶:5'-TGAAAAAGTTTTACAATCTCTAGGTTT-3'(SEQ ID NO:1869)
5'-AAAAGUUUUACAAUCUCUAGGUUUG-3'(SEQ ID NO:5465)
3'-CUUUUUCAAAAUGUUAGAGAUCCAAAC-5'(SEQ ID NO:464)
KRAS-2174靶:5'-GAAAAAGTTTTACAATCTCTAGGTTTG-3'(SEQ ID NO:1870)
5'-AAAGUUUUACAAUCUCUAGGUUUGG-3'(SEQ ID NO:5466)
3'-UUUUUCAAAAUGUUAGAGAUCCAAACC-5'(SEQ ID NO:465)
KRAS-2175靶:5'-AAAAAGTTTTACAATCTCTAGGTTTGG-3'(SEQ ID NO:1871)
5'-UGGUUAAAUUAACAUUGCAUAAACA-3'(SEQ ID NO:5467)
3'-UGACCAAUUUAAUUGUAACGUAUUUGU-5'(SEQ ID NO:466)
KRAS-2216靶:5'-ACTGGTTAAATTAACATTGCATAAACA-3'(SEQ ID NO:1872)
5'-GGUUAAAUUAACAUUGCAUAAACAC-3'(SEQ ID NO:5468)
3'-GACCAAUUUAAUUGUAACGUAUUUGUG-5'(SEQ ID NO:467)
KRAS-2217靶:5'-CTGGTTAAATTAACATTGCATAAACAC-3'(SEQ ID NO:1873)
5'-GUUAAAUUAACAUUGCAUAAACACU-3'(SEQ ID NO:5469)
3'-ACCAAUUUAAUUGUAACGUAUUUGUGA-5'(SEQ ID NO:468)
KRAS-2218靶:5'-TGGTTAAATTAACATTGCATAAACACT-3'(SEQ ID NO:1874)
5'-AUUGCAUAAACACUUUUCAAGUCUG-3'(SEQ ID NO:5470)
3'-UGUAACGUAUUUGUGAAAAGUUCAGAC-5'(SEQ ID NO:469)
KRAS-2229靶:5'-ACATTGCATAAACACTTTTCAAGTCTG-3'(SEQ ID NO:1875)
5'-AAGUCUGAUCCAUAUUUAAUAAUGC-3'(SEQ ID NO:5471)
3'-AGUUCAGACUAGGUAUAAAUUAUUACG-5'(SEQ ID NO:470)
KRAS-2247靶:5'-TCAAGTCTGATCCATATTTAATAATGC-3'(SEQ ID NO:1876)
5'-CAUAUUUAAUAAUGCUUUAAAAUAA-3'(SEQ ID NO:5472)
3'-AGGUAUAAAUUAUUACGAAAUUUUAUU-5'(SEQ ID NO:471)
KRAS-2257靶:5'-TCCATATTTAATAATGCTTTAAAATAA-3'(SEQ ID NO:1877)
5'-AUAUUUAAUAAUGCUUUAAAAUAAA-3'(SEQ ID NO:5473)
3'-GGUAUAAAUUAUUACGAAAUUUUAUUU-5'(SEQ ID NO:472)
KRAS-2258靶:5'-CCATATTTAATAATGCTTTAAAATAAA-3'(SEQ ID NO:1878)
5'-UAUUUAAUAAUGCUUUAAAAUAAAA-3'(SEQ ID NO:5474)
3'-GUAUAAAUUAUUACGAAAUUUUAUUUU-5'(SEQ ID NO:473)
KRAS-2259靶:5'-CATATTTAATAATGCTTTAAAATAAAA-3'(SEQ ID NO:1879)
5'-AUUUAAUAAUGCUUUAAAAUAAAAA-3'(SEQ ID NO:5475)
3'-UAUAAAUUAUUACGAAAUUUUAUUUUU-5'(SEQ ID NO:474)
KRAS-2260靶:5'-ATATTTAATAATGCTTTAAAATAAAAA-3'(SEQ ID NO:1880)
5'-UUUAAUAAUGCUUUAAAAUAAAAAU-3'(SEQ ID NO:5476)
3'-AUAAAUUAUUACGAAAUUUUAUUUUUA-5'(SEQ ID NO:475)
KRAS-2261靶:5'-TATTTAATAATGCTTTAAAATAAAAAT-3'(SEQ ID NO:1881)
5'-UUAAUAAUGCUUUAAAAUAAAAAUA-3'(SEQ ID NO:5477)
3'-UAAAUUAUUACGAAAUUUUAUUUUUAU-5'(SEQ ID NO:476)
KRAS-2262靶:5'-ATTTAATAATGCTTTAAAATAAAAATA-3'(SEQ ID NO:1882)
5'-AAUAAUGCUUUAAAAUAAAAAUAAA-3'(SEQ ID NO:5478)
3'-AAUUAUUACGAAAUUUUAUUUUUAUUU-5'(SEQ ID NO:477)
KRAS-2264靶:5'-TTAATAATGCTTTAAAATAAAAATAAA-3'(SEQ ID NO:1883)
5'-AUAAUGCUUUAAAAUAAAAAUAAAA-3'(SEQ ID NO:5479)
3'-AUUAUUACGAAAUUUUAUUUUUAUUUU-5'(SEQ ID NO:478)
KRAS-2265靶:5'-TAATAATGCTTTAAAATAAAAATAAAA-3'(SEQ ID NO:1884)
5'-UAAUGCUUUAAAAUAAAAAUAAAAA-3'(SEQ ID NO:5480)
3'-UUAUUACGAAAUUUUAUUUUUAUUUUU-5'(SEQ ID NO:479)
KRAS-2266靶:5'-AATAATGCTTTAAAATAAAAATAAAAA-3'(SEQ ID NO:1885)
5'-AAUGCUUUAAAAUAAAAAUAAAAAC-3'(SEQ ID NO:5481)
3'-UAUUACGAAAUUUUAUUUUUAUUUUUG-5'(SEQ ID NO:480)
KRAS-2267靶:5'-ATAATGCTTTAAAATAAAAATAAAAAC-3'(SEQ ID NO:1886)
5'-UAAAAUAAAAAUAAAAACAAUCCUU-3'(SEQ ID NO:5482)
3'-AAAUUUUAUUUUUAUUUUUGUUAGGAA-5'(SEQ ID NO:481)
KRAS-2274靶:5'-TTTAAAATAAAAATAAAAACAATCCTT-3'(SEQ ID NO:1887)
5'-AAAAAUAAAAACAAUCCUUUUGAUA-3'(SEQ ID NO:5483)
3'-UAUUUUUAUUUUUGUUAGGAAAACUAU-5'(SEQ ID NO:482)
KRAS-2280靶:5'-ATAAAAATAAAAACAATCCTTTTGATA-3'(SEQ ID NO:1888)
5'-AAAAUAAAAACAAUCCUUUUGAUAA-3'(SEQ ID NO:5484)
3'-AUUUUUAUUUUUGUUAGGAAAACUAUU-5'(SEQ ID NO:483)
KRAS-2281靶:5'-TAAAAATAAAAACAATCCTTTTGATAA-3'(SEQ ID NO:1889)
5'-AAAUAAAAACAAUCCUUUUGAUAAA-3'(SEQ ID NO:5485)
3'-UUUUUAUUUUUGUUAGGAAAACUAUUU-5'(SEQ ID NO:484)
KRAS-2282靶:5'-AAAAATAAAAACAATCCTTTTGATAAA-3'(SEQ ID NO:1890)
5'-AAUAAAAACAAUCCUUUUGAUAAAU-3'(SEQ ID NO:5486)
3'-UUUUAUUUUUGUUAGGAAAACUAUUUA-5'(SEQ ID NO:485)
KRAS-2283靶:5'-AAAATAAAAACAATCCTTTTGATAAAT-3'(SEQ ID NO:1891)
5'-AUAAAAACAAUCCUUUUGAUAAAUU-3'(SEQ ID NO:5487)
3'-UUUAUUUUUGUUAGGAAAACUAUUUAA-5'(SEQ ID NO:486)
KRAS-2284靶:5'-AAATAAAAACAATCCTTTTGATAAATT-3'(SEQ ID NO:1892)
5'-UAAAAACAAUCCUUUUGAUAAAUUU-3'(SEQ ID NO:5488)
3'-UUAUUUUUGUUAGGAAAACUAUUUAAA-5'(SEQ ID NO:487)
KRAS-2285靶:5'-AATAAAAACAATCCTTTTGATAAATTT-3'(SEQ ID NO:1893)
5'-AAAAACAAUCCUUUUGAUAAAUUUA-3'(SEQ ID NO:5489)
3'-UAUUUUUGUUAGGAAAACUAUUUAAAU-5'(SEQ ID NO:488)
KRAS-2286靶:5'-ATAAAAACAATCCTTTTGATAAATTTA-3'(SEQ ID NO:1894)
5'-AAAACAAUCCUUUUGAUAAAUUUAA-3'(SEQ ID NO:5490)
3'-AUUUUUGUUAGGAAAACUAUUUAAAUU-5'(SEQ ID NO:489)
KRAS-2287靶:5'-TAAAAACAATCCTTTTGATAAATTTAA-3'(SEQ ID NO:1895)
5'-CAAUCCUUUUGAUAAAUUUAAAAUG-3'(SEQ ID NO:5491)
3'-UUGUUAGGAAAACUAUUUAAAUUUUAC-5'(SEQ ID NO:490)
KRAS-2291靶:5'-AACAATCCTTTTGATAAATTTAAAATG-3'(SEQ ID NO:1896)
5'-CUUUUGAUAAAUUUAAAAUGUUACU-3'(SEQ ID NO:5492)
3'-AGGAAAACUAUUUAAAUUUUACAAUGA-5'(SEQ ID NO:491)
KRAS-2296靶:5'-TCCTTTTGATAAATTTAAAATGTTACT-3'(SEQ ID NO:1897)
5'-UUUUGAUAAAUUUAAAAUGUUACUU-3'(SEQ ID NO:5493)
3'-GGAAAACUAUUUAAAUUUUACAAUGAA-5'(SEQ ID NO:492)
KRAS-2297靶:5'-CCTTTTGATAAATTTAAAATGTTACTT-3'(SEQ ID NO:1898)
5'-UUUGAUAAAUUUAAAAUGUUACUUA-3'(SEQ ID NO:5494)
3'-GAAAACUAUUUAAAUUUUACAAUGAAU-5'(SEQ ID NO:493)
KRAS-2298靶:5'-CTTTTGATAAATTTAAAATGTTACTTA-3'(SEQ ID NO:1899)
5'-AUAAAUUUAAAAUGUUACUUAUUUU-3'(SEQ ID NO:5495)
3'-ACUAUUUAAAUUUUACAAUGAAUAAAA-5'(SEQ ID NO:494)
KRAS-2302靶:5'-TGATAAATTTAAAATGTTACTTATTTT-3'(SEQ ID NO:1900)
5'-UAAAUUUAAAAUGUUACUUAUUUUA-3'(SEQ ID NO:5496)
3'-CUAUUUAAAUUUUACAAUGAAUAAAAU-5'(SEQ ID NO:495)
KRAS-2303靶:5'-GATAAATTTAAAATGTTACTTATTTTA-3'(SEQ ID NO:1901)
5'-AAAUUUAAAAUGUUACUUAUUUUAA-3'(SEQ ID NO:5497)
3'-UAUUUAAAUUUUACAAUGAAUAAAAUU-5'(SEQ ID NO:496)
KRAS-2304靶:5'-ATAAATTTAAAATGTTACTTATTTTAA-3'(SEQ ID NO:1902)
5'-AAUUUAAAAUGUUACUUAUUUUAAA-3'(SEQ ID NO:5498)
3'-AUUUAAAUUUUACAAUGAAUAAAAUUU-5'(SEQ ID NO:497)
KRAS-2305靶:5'-TAAATTTAAAATGTTACTTATTTTAAA-3'(SEQ ID NO:1903)
5'-AUUUAAAAUGUUACUUAUUUUAAAA-3'(SEQ ID NO:5499)
3'-UUUAAAUUUUACAAUGAAUAAAAUUUU-5'(SEQ ID NO:498)
KRAS-2306靶:5'-AAATTTAAAATGTTACTTATTTTAAAA-3'(SEQ ID NO:1904)
5'-UUUAAAAUGUUACUUAUUUUAAAAU-3'(SEQ ID NO:5500)
3'-UUAAAUUUUACAAUGAAUAAAAUUUUA-5'(SEQ ID NO:499)
KRAS-2307靶:5'-AATTTAAAATGTTACTTATTTTAAAAT-3'(SEQ ID NO:1905)
5'-UAAAAUGUUACUUAUUUUAAAAUAA-3'(SEQ ID NO:5501)
3'-AAAUUUUACAAUGAAUAAAAUUUUAUU-5'(SEQ ID NO:500)
KRAS-2309靶:5'-TTTAAAATGTTACTTATTTTAAAATAA-3'(SEQ ID NO:1906)
5'-AAAAUGUUACUUAUUUUAAAAUAAA-3'(SEQ ID NO:5502)
3'-AAUUUUACAAUGAAUAAAAUUUUAUUU-5'(SEQ ID NO:501)
KRAS-2310靶:5'-TTAAAATGTTACTTATTTTAAAATAAA-3'(SEQ ID NO:1907)
5'-AAAUGUUACUUAUUUUAAAAUAAAU-3'(SEQ ID NO:5503)
3'-AUUUUACAAUGAAUAAAAUUUUAUUUA-5'(SEQ ID NO:502)
KRAS-2311靶:5'-TAAAATGTTACTTATTTTAAAATAAAT-3'(SEQ ID NO:1908)
5'-AAUGUUACUUAUUUUAAAAUAAAUG-3'(SEQ ID NO:5504)
3'-UUUUACAAUGAAUAAAAUUUUAUUUAC-5'(SEQ ID NO:503)
KRAS-2312靶:5'-AAAATGTTACTTATTTTAAAATAAATG-3'(SEQ ID NO:1909)
5'-AUGUUACUUAUUUUAAAAUAAAUGA-3'(SEQ ID NO:5505)
3'-UUUACAAUGAAUAAAAUUUUAUUUACU-5'(SEQ ID NO:504)
KRAS-2313靶:5'-AAATGTTACTTATTTTAAAATAAATGA-3'(SEQ ID NO:1910)
5'-GUUACUUAUUUUAAAAUAAAUGAAG-3'(SEQ ID NO:5506)
3'-UACAAUGAAUAAAAUUUUAUUUACUUC-5'(SEQ ID NO:505)
KRAS-2315靶:5'-ATGTTACTTATTTTAAAATAAATGAAG-3'(SEQ ID NO:1911)
5'-UUAUUUUAAAAUAAAUGAAGUGAGA-3'(SEQ ID NO:5507)
3'-UGAAUAAAAUUUUAUUUACUUCACUCU-5'(SEQ ID NO:506)
KRAS-2320靶:5'-ACTTATTTTAAAATAAATGAAGTGAGA-3'(SEQ ID NO:1912)
5'-AUUUUAAAAUAAAUGAAGUGAGAUG-3'(SEQ ID NO:5508)
3'-AAUAAAAUUUUAUUUACUUCACUCUAC-5'(SEQ ID NO:507)
KRAS-2322靶:5'-TTATTTTAAAATAAATGAAGTGAGATG-3'(SEQ ID NO:1913)
5'-UUUUAAAAUAAAUGAAGUGAGAUGG-3'(SEQ ID NO:5509)
3'-AUAAAAUUUUAUUUACUUCACUCUACC-5'(SEQ ID NO:508)
KRAS-2323靶:5'-TATTTTAAAATAAATGAAGTGAGATGG-3'(SEQ ID NO:1914)
5'-UAAAAUAAAUGAAGUGAGAUGGCAU-3'(SEQ ID NO:5510)
3'-AAAUUUUAUUUACUUCACUCUACCGUA-5'(SEQ ID NO:509)
KRAS-2326靶:5'-TTTAAAATAAATGAAGTGAGATGGCAT-3'(SEQ ID NO:1915)
5'-AAAAUAAAUGAAGUGAGAUGGCAUG-3'(SEQ ID NO:5511)
3'-AAUUUUAUUUACUUCACUCUACCGUAC-5'(SEQ ID NO:510)
KRAS-2327靶:5'-TTAAAATAAATGAAGTGAGATGGCATG-3'(SEQ ID NO:1916)
5'-CAUUUCUUCAUGUUAAAAGAAGUCA-3'(SEQ ID NO:5512)
3'-AGGUAAAGAAGUACAAUUUUCUUCAGU-5'(SEQ ID NO:511)
KRAS-2447靶:5'-TCCATTTCTTCATGTTAAAAGAAGTCA-3'(SEQ ID NO:1917)
5'-AUUUCUUCAUGUUAAAAGAAGUCAU-3'(SEQ ID NO:5513)
3'-GGUAAAGAAGUACAAUUUUCUUCAGUA-5'(SEQ ID NO:512)
KRAS-2448靶:5'-CCATTTCTTCATGTTAAAAGAAGTCAT-3'(SEQ ID NO:1918)
5'-CAAACUCUUAGUUUUUUUUUUUUAC-3'(SEQ ID NO:5514)
3'-GAGUUUGAGAAUCAAAAAAAAAAAAUG-5'(SEQ ID NO:513)
KRAS-2475靶:5'-CTCAAACTCTTAGTTTTTTTTTTTTAC-3'(SEQ ID NO:1919)
5'-GUUUUUUUUUUUUACAACUAUGUAA-3'(SEQ ID NO:5515)
3'-AUCAAAAAAAAAAAAUGUUGAUACAUU-5'(SEQ ID NO:514)
KRAS-2485靶:5'-TAGTTTTTTTTTTTTACAACTATGTAA-3'(SEQ ID NO:1920)
5'-UUUUUUUUUUUUACAACUAUGUAAU-3'(SEQ ID NO:5516)
3'-UCAAAAAAAAAAAAUGUUGAUACAUUA-5'(SEQ ID NO:515)
KRAS-2486靶:5'-AGTTTTTTTTTTTTACAACTATGTAAT-3'(SEQ ID NO:1921)
5'-UUUUUUUUUUUACAACUAUGUAAUU-3'(SEQ ID NO:5517)
3'-CAAAAAAAAAAAAUGUUGAUACAUUAA-5'(SEQ ID NO:516)
KRAS-2487靶:5'-GTTTTTTTTTTTTACAACTATGTAATT-3'(SEQ ID NO:1922)
5'-UUUUUUUUUUACAACUAUGUAAUUU-3'(SEQ ID NO:5518)
3'-AAAAAAAAAAAAUGUUGAUACAUUAAA-5'(SEQ ID NO:517)
KRAS-2488靶:5'-TTTTTTTTTTTTACAACTATGTAATTT-3'(SEQ ID NO:1923)
5'-UUUUUUUUUACAACUAUGUAAUUUA-3'(SEQ ID NO:5519)
3'-AAAAAAAAAAAUGUUGAUACAUUAAAU-5'(SEQ ID NO:518)
KRAS-2489靶:5'-TTTTTTTTTTTACAACTATGTAATTTA-3'(SEQ ID NO:1924)
5'-UUUUUUUUACAACUAUGUAAUUUAU-3'(SEQ ID NO:5520)
3'-AAAAAAAAAAUGUUGAUACAUUAAAUA-5'(SEQ ID NO:519)
KRAS-2490靶:5'-TTTTTTTTTTACAACTATGTAATTTAT-3'(SEQ ID NO:1925)
5'-UUUUUUUACAACUAUGUAAUUUAUA-3'(SEQ ID NO:5521)
3'-AAAAAAAAAUGUUGAUACAUUAAAUAU-5'(SEQ ID NO:520)
KRAS-2491靶:5'-TTTTTTTTTACAACTATGTAATTTATA-3'(SEQ ID NO:1926)
5'-UUUUUUACAACUAUGUAAUUUAUAU-3'(SEQ ID NO:5522)
3'-AAAAAAAAUGUUGAUACAUUAAAUAUA-5'(SEQ ID NO:521)
KRAS-2492靶:5'-TTTTTTTTACAACTATGTAATTTATAT-3'(SEQ ID NO:1927)
5'-UUUUUACAACUAUGUAAUUUAUAUU-3'(SEQ ID NO:5523)
3'-AAAAAAAUGUUGAUACAUUAAAUAUAA-5'(SEQ ID NO:522)
KRAS-2493靶:5'-TTTTTTTACAACTATGTAATTTATATT-3'(SEQ ID NO:1928)
5'-UUUUACAACUAUGUAAUUUAUAUUC-3'(SEQ ID NO:5524)
3'-AAAAAAUGUUGAUACAUUAAAUAUAAG-5'(SEQ ID NO:523)
KRAS-2494靶:5'-TTTTTTACAACTATGTAATTTATATTC-3'(SEQ ID NO:1929)
5'-UUUACAACUAUGUAAUUUAUAUUCC-3'(SEQ ID NO:5525)
3'-AAAAAUGUUGAUACAUUAAAUAUAAGG-5'(SEQ ID NO:524)
KRAS-2495靶:5'-TTTTTACAACTATGTAATTTATATTCC-3'(SEQ ID NO:1930)
5'-CUAUGUAAUUUAUAUUCCAUUUACA-3'(SEQ ID NO:5526)
3'-UUGAUACAUUAAAUAUAAGGUAAAUGU-5'(SEQ ID NO:525)
KRAS-2502靶:5'-AACTATGTAATTTATATTCCATTTACA-3'(SEQ ID NO:1931)
5'-UAUGUAAUUUAUAUUCCAUUUACAU-3'(SEQ ID NO:5527)
3'-UGAUACAUUAAAUAUAAGGUAAAUGUA-5'(SEQ ID NO:526)
KRAS-2503靶:5'-ACTATGTAATTTATATTCCATTTACAT-3'(SEQ ID NO:1932)
5'-AUGUAAUUUAUAUUCCAUUUACAUA-3'(SEQ ID NO:5528)
3'-GAUACAUUAAAUAUAAGGUAAAUGUAU-5'(SEQ ID NO:527)
KRAS-2504靶:5'-CTATGTAATTTATATTCCATTTACATA-3'(SEQ ID NO:1933)
5'-UUUAUAUUCCAUUUACAUAAGGAUA-3'(SEQ ID NO:5529)
3'-UUAAAUAUAAGGUAAAUGUAUUCCUAU-5'(SEQ ID NO:528)
KRAS-2510靶:5'-AATTTATATTCCATTTACATAAGGATA-3'(SEQ ID NO:1934)
5'-UUAUAUUCCAUUUACAUAAGGAUAC-3'(SEQ ID NO:5530)
3'-UAAAUAUAAGGUAAAUGUAUUCCUAUG-5'(SEQ ID NO:529)
KRAS-2511靶:5'-ATTTATATTCCATTTACATAAGGATAC-3'(SEQ ID NO:1935)
5'-UAUAUUCCAUUUACAUAAGGAUACA-3'(SEQ ID NO:5531)
3'-AAAUAUAAGGUAAAUGUAUUCCUAUGU-5'(SEQ ID NO:530)
KRAS-2512靶:5'-TTTATATTCCATTTACATAAGGATACA-3'(SEQ ID NO:1936)
5'-AUAUUCCAUUUACAUAAGGAUACAC-3'(SEQ ID NO:5532)
3'-AAUAUAAGGUAAAUGUAUUCCUAUGUG-5'(SEQ ID NO:531)
KRAS-2513靶:5'-TTATATTCCATTTACATAAGGATACAC-3'(SEQ ID NO:1937)
5'-CAUAAGGAUACACUUAUUUGUCAAG-3'(SEQ ID NO:5533)
3'-AUGUAUUCCUAUGUGAAUAAACAGUUC-5'(SEQ ID NO:532)
KRAS-2525靶:5'-TACATAAGGATACACTTATTTGTCAAG-3'(SEQ ID NO:1938)
5'-AGGAUACACUUAUUUGUCAAGCUCA-3'(SEQ ID NO:5534)
3'-AUUCCUAUGUGAAUAAACAGUUCGAGU-5'(SEQ ID NO:533)
KRAS-2529靶:5'-TAAGGATACACTTATTTGTCAAGCTCA-3'(SEQ ID NO:1939)
5'-CUGUAAAUUUUUAACCUAUGUUACA-3'(SEQ ID NO:5535)
3'-UAGACAUUUAAAAAUUGGAUACAAUGU-5'(SEQ ID NO:534)
KRAS-2561靶:5'-ATCTGTAAATTTTTAACCTATGTTACA-3'(SEQ ID NO:1940)
5'-UGUAAAUUUUUAACCUAUGUUACAC-3'(SEQ ID NO:5536)
3'-AGACAUUUAAAAAUUGGAUACAAUGUG-5'(SEQ ID NO:535)
KRAS-2562靶:5'-TCTGTAAATTTTTAACCTATGTTACAC-3'(SEQ ID NO:1941)
5'-GUAAAUUUUUAACCUAUGUUACACC-3'(SEQ ID NO:5537)
3'-GACAUUUAAAAAUUGGAUACAAUGUGG-5'(SEQ ID NO:536)
KRAS-2563靶:5'-CTGTAAATTTTTAACCTATGTTACACC-3'(SEQ ID NO:1942)
5'-CAAGAGGUGAAGUUUAUAUUUGAAU-3'(SEQ ID NO:5538)
3'-ACGUUCUCCACUUCAAAUAUAAACUUA-5'(SEQ ID NO:537)
KRAS-2619靶:5'-TGCAAGAGGTGAAGTTTATATTTGAAT-3'(SEQ ID NO:1943)
5'-AGAGGUGAAGUUUAUAUUUGAAUAU-3'(SEQ ID NO:5539)
3'-GUUCUCCACUUCAAAUAUAAACUUAUA-5'(SEQ ID NO:538)
KRAS-2621靶:5'-CAAGAGGTGAAGTTTATATTTGAATAT-3'(SEQ ID NO:1944)
5'-GAGGUGAAGUUUAUAUUUGAAUAUC-3'(SEQ ID NO:5540)
3'-UUCUCCACUUCAAAUAUAAACUUAUAG-5'(SEQ ID NO:539)
KRAS-2622靶:5'-AAGAGGTGAAGTTTATATTTGAATATC-3'(SEQ ID NO:1945)
5'-GGUGAAGUUUAUAUUUGAAUAUCCA-3'(SEQ ID NO:5541)
3'-CUCCACUUCAAAUAUAAACUUAUAGGU-5'(SEQ ID NO:540)
KRAS-2624靶:5'-GAGGTGAAGTTTATATTTGAATATCCA-3'(SEQ ID NO:1946)
5'-GUGAAGUUUAUAUUUGAAUAUCCAU-3'(SEQ ID NO:5542)
3'-UCCACUUCAAAUAUAAACUUAUAGGUA-5'(SEQ ID NO:541)
KRAS-2625靶:5'-AGGTGAAGTTTATATTTGAATATCCAT-3'(SEQ ID NO:1947)
5'-GUUUAUAUUUGAAUAUCCAUUCUCG-3'(SEQ ID NO:5543)
3'-UUCAAAUAUAAACUUAUAGGUAAGAGC-5'(SEQ ID NO:542)
KRAS-2630靶:5'-AAGTTTATATTTGAATATCCATTCTCG-3'(SEQ ID NO:1948)
5'-UUGAUGCAGUUUUAAUACUUGUAAU-3'(SEQ ID NO:5544)
3'-UGAACUACGUCAAAAUUAUGAACAUUA-5'(SEQ ID NO:543)
KRAS-2718靶:5'-ACTTGATGCAGTTTTAATACTTGTAAT-3'(SEQ ID NO:1949)
5'-GAUGCAGUUUUAAUACUUGUAAUUC-3'(SEQ ID NO:5545)
3'-AACUACGUCAAAAUUAUGAACAUUAAG-5'(SEQ ID NO:544)
KRAS-2720靶:5'-TTGATGCAGTTTTAATACTTGTAATTC-3'(SEQ ID NO:1950)
5'-UUUGACCUAAUCACUAAUUUUCAGG-3'(SEQ ID NO:5546)
3'-CUAAACUGGAUUAGUGAUUAAAAGUCC-5'(SEQ ID NO:545)
KRAS-2871靶:5'-GATTTGACCTAATCACTAATTTTCAGG-3'(SEQ ID NO:1951)
5'-CUAAUCACUAAUUUUCAGGUGGUGG-3'(SEQ ID NO:5547)
3'-UGGAUUAGUGAUUAAAAGUCCACCACC-5'(SEQ ID NO:546)
KRAS-2877靶:5'-ACCTAATCACTAATTTTCAGGTGGTGG-3'(SEQ ID NO:1952)
5'-GUAGGAUUUUUCAAACCUGGUAUGA-3'(SEQ ID NO:5548)
3'-GUCAUCCUAAAAAGUUUGGACCAUACU-5'(SEQ ID NO:547)
KRAS-2946靶:5'-CAGTAGGATTTTTCAAACCTGGTATGA-3'(SEQ ID NO:1953)
5'-UGGAAGGAGAAUUUAAUAAAGAUAG-3'(SEQ ID NO:5549)
3'-UCACCUUCCUCUUAAAUUAUUUCUAUC-5'(SEQ ID NO:548)
KRAS-2991靶:5'-AGTGGAAGGAGAATTTAATAAAGATAG-3'(SEQ ID NO:1954)
5'-AAGGAGAAUUUAAUAAAGAUAGUGC-3'(SEQ ID NO:5550)
3'-CCUUCCUCUUAAAUUAUUUCUAUCACG-5'(SEQ ID NO:549)
KRAS-2994靶:5'-GGAAGGAGAATTTAATAAAGATAGTGC-3'(SEQ ID NO:1955)
5'-GGAGAAUUUAAUAAAGAUAGUGCUG-3'(SEQ ID NO:5551)
3'-UUCCUCUUAAAUUAUUUCUAUCACGAC-5'(SEQ ID NO:550)
KRAS-2996靶:5'-AAGGAGAATTTAATAAAGATAGTGCTG-3'(SEQ ID NO:1956)
5'-GAGAAUUUAAUAAAGAUAGUGCUGA-3'(SEQ ID NO:5552)
3'-UCCUCUUAAAUUAUUUCUAUCACGACU-5'(SEQ ID NO:551)
KRAS-2997靶:5'-AGGAGAATTTAATAAAGATAGTGCTGA-3'(SEQ ID NO:1957)
5'-AUUUAAUAAAGAUAGUGCUGAAAGA-3'(SEQ ID NO:5553)
3'-CUUAAAUUAUUUCUAUCACGACUUUCU-5'(SEQ ID NO:552)
KRAS-3001靶:5'-GAATTTAATAAAGATAGTGCTGAAAGA-3'(SEQ ID NO:1958)
5'-CUUAGGUAAUCUAUAACUAGGACUA-3'(SEQ ID NO:5554)
3'-AGGAAUCCAUUAGAUAUUGAUCCUGAU-5'(SEQ ID NO:553)
KRAS-3030靶:5'-TCCTTAGGTAATCTATAACTAGGACTA-3'(SEQ ID NO:1959)
5'-UUAGGUAAUCUAUAACUAGGACUAC-3'(SEQ ID NO:5555)
3'-GGAAUCCAUUAGAUAUUGAUCCUGAUG-5'(SEQ ID NO:554)
KRAS-3031靶:5'-CCTTAGGTAATCTATAACTAGGACTAC-3'(SEQ ID NO:1960)
5'-CAGUAAUACAUUCCAUUGUUUUAGU-3'(SEQ ID NO:5556)
3'-UUGUCAUUAUGUAAGGUAACAAAAUCA-5'(SEQ ID NO:555)
KRAS-3065靶:5'-AACAGTAATACATTCCATTGTTTTAGT-3'(SEQ ID NO:1961)
5'-GUAAUACAUUCCAUUGUUUUAGUAA-3'(SEQ ID NO:5557)
3'-GUCAUUAUGUAAGGUAACAAAAUCAUU-5'(SEQ ID NO:556)
KRAS-3067靶:5'-CAGTAATACATTCCATTGTTTTAGTAA-3'(SEQ ID NO:1962)
5'-UAAUACAUUCCAUUGUUUUAGUAAC-3'(SEQ ID NO:5558)
3'-UCAUUAUGUAAGGUAACAAAAUCAUUG-5'(SEQ ID NO:557)
KRAS-3068靶:5'-AGTAATACATTCCATTGTTTTAGTAAC-3'(SEQ ID NO:1963)
5'-AAUACAUUCCAUUGUUUUAGUAACC-3'(SEQ ID NO:5559)
3'-CAUUAUGUAAGGUAACAAAAUCAUUGG-5'(SEQ ID NO:558)
KRAS-3069靶:5'-GTAATACATTCCATTGTTTTAGTAACC-3'(SEQ ID NO:1964)
5'-AUUGUUUUAGUAACCAGAAAUCUUC-3'(SEQ ID NO:5560)
3'-GGUAACAAAAUCAUUGGUCUUUAGAAG-5'(SEQ ID NO:559)
KRAS-3079靶:5'-CCATTGTTTTAGTAACCAGAAATCTTC-3'(SEQ ID NO:1965)
5'-CAGAAAUCUUCAUGCAAUGAAAAAU-3'(SEQ ID NO:5561)
3'-UGGUCUUUAGAAGUACGUUACUUUUUA-5'(SEQ ID NO:560)
KRAS-3093靶:5'-ACCAGAAATCTTCATGCAATGAAAAAT-3'(SEQ ID NO:1966)
5'-CAUGCAAUGAAAAAUACUUUAAUUC-3'(SEQ ID NO:5562)
3'-AAGUACGUUACUUUUUAUGAAAUUAAG-5'(SEQ ID NO:561)
KRAS-3103靶:5'-TTCATGCAATGAAAAATACTTTAATTC-3'(SEQ ID NO:1967)
5'-UGAAAAAUACUUUAAUUCAUGAAGC-3'(SEQ ID NO:5563)
3'-UUACUUUUUAUGAAAUUAAGUACUUCG-5'(SEQ ID NO:562)
KRAS-3110靶:5'-AATGAAAAATACTTTAATTCATGAAGC-3'(SEQ ID NO:1968)
5'-AAAAAUACUUUAAUUCAUGAAGCUU-3'(SEQ ID NO:5564)
3'-ACUUUUUAUGAAAUUAAGUACUUCGAA-5'(SEQ ID NO:563)
KRAS-3112靶:5'-TGAAAAATACTTTAATTCATGAAGCTT-3'(SEQ ID NO:1969)
5'-AAAAUACUUUAAUUCAUGAAGCUUA-3'(SEQ ID NO:5565)
3'-CUUUUUAUGAAAUUAAGUACUUCGAAU-5'(SEQ ID NO:564)
KRAS-3113靶:5'-GAAAAATACTTTAATTCATGAAGCTTA-3'(SEQ ID NO:1970)
5'-CAUGAAGCUUACUUUUUUUUUUUGG-3'(SEQ ID NO:5566)
3'-AAGUACUUCGAAUGAAAAAAAAAAACC-5'(SEQ ID NO:565)
KRAS-3127靶:5'-TTCATGAAGCTTACTTTTTTTTTTTGG-3'(SEQ ID NO:1971)
5'-GAAGCUUACUUUUUUUUUUUGGUGU-3'(SEQ ID NO:5567)
3'-UACUUCGAAUGAAAAAAAAAAACCACA-5'(SEQ ID NO:566)
KRAS-3130靶:5'-ATGAAGCTTACTTTTTTTTTTTGGTGT-3'(SEQ ID NO:1972)
5'-CUUACUUUUUUUUUUUGGUGUCAGA-3'(SEQ ID NO:5568)
3'-UCGAAUGAAAAAAAAAAACCACAGUCU-5'(SEQ ID NO:567)
KRAS-3134靶:5'-AGCTTACTTTTTTTTTTTGGTGTCAGA-3'(SEQ ID NO:1973)
5'-CUUUUUUUUUUUGGUGUCAGAGUCU-3'(SEQ ID NO:5569)
3'-AUGAAAAAAAAAAACCACAGUCUCAGA-5'(SEQ ID NO:568)
KRAS-3138靶:5'-TACTTTTTTTTTTTGGTGTCAGAGTCT-3'(SEQ ID NO:1974)
5'-UUUUUUUUUUUGGUGUCAGAGUCUC-3'(SEQ ID NO:5570)
3'-UGAAAAAAAAAAACCACAGUCUCAGAG-5'(SEQ ID NO:569)
KRAS-3139靶:5'-ACTTTTTTTTTTTGGTGTCAGAGTCTC-3'(SEQ ID NO:1975)
5'-CUAAUUUUUGUAUUUUUAGGAGAGA-3'(SEQ ID NO:5571)
3'-UUGAUUAAAAACAUAAAAAUCCUCUCU-5'(SEQ ID NO:570)
KRAS-3297靶:5'-AACTAATTTTTGTATTTTTAGGAGAGA-3'(SEQ ID NO:1976)
5'-AUUUUUGUAUUUUUAGGAGAGACGG-3'(SEQ ID NO:5572)
3'-AUUAAAAACAUAAAAAUCCUCUCUGCC-5'(SEQ ID NO:571)
KRAS-3300靶:5'-TAATTTTTGTATTTTTAGGAGAGACGG-3'(SEQ ID NO:1977)
5'-CAUUUAUUCAGCAAAUAUUUAUUGA-3'(SEQ ID NO:5573)
3'-GAGUAAAUAAGUCGUUUAUAAAUAACU-5'(SEQ ID NO:572)
KRAS-3413靶:5'-CTCATTTATTCAGCAAATATTTATTGA-3'(SEQ ID NO:1978)
5'-UUUAUUCAGCAAAUAUUUAUUGAGU-3'(SEQ ID NO:5574)
3'-GUAAAUAAGUCGUUUAUAAAUAACUCA-5'(SEQ ID NO:573)
KRAS-3415靶:5'-CATTTATTCAGCAAATATTTATTGAGT-3'(SEQ ID NO:1979)
5'-UAUUCAGCAAAUAUUUAUUGAGUGC-3'(SEQ ID NO:5575)
3'-AAAUAAGUCGUUUAUAAAUAACUCACG-5'(SEQ ID NO:574)
KRAS-3417靶:5'-TTTATTCAGCAAATATTTATTGAGTGC-3'(SEQ ID NO:1980)
5'-UUUUAGUUUUGCAAAGAAGGGGUUU-3'(SEQ ID NO:5576)
3'-AUAAAAUCAAAACGUUUCUUCCCCAAA-5'(SEQ ID NO:575)
KRAS-3589靶:5'-TATTTTAGTTTTGCAAAGAAGGGGTTT-3'(SEQ ID NO:1981)
5'-CUAUAAUUGUUUUGCUACGAUUCCA-3'(SEQ ID NO:5577)
3'-GAGAUAUUAACAAAACGAUGCUAAGGU-5'(SEQ ID NO:576)
KRAS-3630靶:5'-CTCTATAATTGTTTTGCTACGATTCCA-3'(SEQ ID NO:1982)
5'-CUUUAUGUAAAUCACUUCAUUGUUU-3'(SEQ ID NO:5578)
3'-AUGAAAUACAUUUAGUGAAGUAACAAA-5'(SEQ ID NO:577)
KRAS-3677靶:5'-TACTTTATGTAAATCACTTCATTGTTT-3'(SEQ ID NO:1983)
5'-UUUAUGUAAAUCACUUCAUUGUUUU-3'(SEQ ID NO:5579)
3'-UGAAAUACAUUUAGUGAAGUAACAAAA-5'(SEQ ID NO:578)
KRAS-3678靶:5'-ACTTTATGTAAATCACTTCATTGTTTT-3'(SEQ ID NO:1984)
5'-UUAUGUAAAUCACUUCAUUGUUUUA-3'(SEQ ID NO:5580)
3'-GAAAUACAUUUAGUGAAGUAACAAAAU-5'(SEQ ID NO:579)
KRAS-3679靶:5'-CTTTATGTAAATCACTTCATTGTTTTA-3'(SEQ ID NO:1985)
5'-UAUGUAAAUCACUUCAUUGUUUUAA-3'(SEQ ID NO:5581)
3'-AAAUACAUUUAGUGAAGUAACAAAAUU-5'(SEQ ID NO:580)
KRAS-3680靶:5'-TTTATGTAAATCACTTCATTGTTTTAA-3'(SEQ ID NO:1986)
5'-AUGUAAAUCACUUCAUUGUUUUAAA-3'(SEQ ID NO:5582)
3'-AAUACAUUUAGUGAAGUAACAAAAUUU-5'(SEQ ID NO:581)
KRAS-3681靶:5'-TTATGTAAATCACTTCATTGTTTTAAA-3'(SEQ ID NO:1987)
5'-UGUAAAUCACUUCAUUGUUUUAAAG-3'(SEQ ID NO:5583)
3'-AUACAUUUAGUGAAGUAACAAAAUUUC-5'(SEQ ID NO:582)
KRAS-3682靶:5'-TATGTAAATCACTTCATTGTTTTAAAG-3'(SEQ ID NO:1988)
5'-GUAAAUCACUUCAUUGUUUUAAAGG-3'(SEQ ID NO:5584)
3'-UACAUUUAGUGAAGUAACAAAAUUUCC-5'(SEQ ID NO:583)
KRAS-3683靶:5'-ATGTAAATCACTTCATTGTTTTAAAGG-3'(SEQ ID NO:1989)
5'-UGUUUUAAAGGAAUAAACUUGAUUA-3'(SEQ ID NO:5585)
3'-UAACAAAAUUUCCUUAUUUGAACUAAU-5'(SEQ ID NO:584)
KRAS-3697靶:5'-ATTGTTTTAAAGGAATAAACTTGATTA-3'(SEQ ID NO:1990)
5'-GUUUUAAAGGAAUAAACUUGAUUAU-3'(SEQ ID NO:5586)
3'-AACAAAAUUUCCUUAUUUGAACUAAUA-5'(SEQ ID NO:585)
KRAS-3698靶:5'-TTGTTTTAAAGGAATAAACTTGATTAT-3'(SEQ ID NO:1991)
5'-UUAAAGGAAUAAACUUGAUUAUAUU-3'(SEQ ID NO:5587)
3'-AAAAUUUCCUUAUUUGAACUAAUAUAA-5'(SEQ ID NO:586)
KRAS-3701靶:5'-TTTTAAAGGAATAAACTTGATTATATT-3'(SEQ ID NO:1992)
5'-UAAAGGAAUAAACUUGAUUAUAUUG-3'(SEQ ID NO:5588)
3'-AAAUUUCCUUAUUUGAACUAAUAUAAC-5'(SEQ ID NO:587)
KRAS-3702靶:5'-TTTAAAGGAATAAACTTGATTATATTG-3'(SEQ ID NO:1993)
5'-AAAGGAAUAAACUUGAUUAUAUUGU-3'(SEQ ID NO:5589)
3'-AAUUUCCUUAUUUGAACUAAUAUAACA-5'(SEQ ID NO:588)
KRAS-3703靶:5'-TTAAAGGAATAAACTTGATTATATTGT-3'(SEQ ID NO:1994)
5'-AGGAAUAAACUUGAUUAUAUUGUUU-3'(SEQ ID NO:5590)
3'-UUUCCUUAUUUGAACUAAUAUAACAAA-5'(SEQ ID NO:589)
KRAS-3705靶:5'-AAAGGAATAAACTTGATTATATTGTTT-3'(SEQ ID NO:1995)
5'-GGAAUAAACUUGAUUAUAUUGUUUU-3'(SEQ ID NO:5591)
3'-UUCCUUAUUUGAACUAAUAUAACAAAA-5'(SEQ ID NO:590)
KRAS-3706靶:5'-AAGGAATAAACTTGATTATATTGTTTT-3'(SEQ ID NO:1996)
5'-GAAUAAACUUGAUUAUAUUGUUUUU-3'(SEQ ID NO:5592)
3'-UCCUUAUUUGAACUAAUAUAACAAAAA-5'(SEQ ID NO:591)
KRAS-3707靶:5'-AGGAATAAACTTGATTATATTGTTTTT-3'(SEQ ID NO:1997)
5'-AAUAAACUUGAUUAUAUUGUUUUUU-3'(SEQ ID NO:5593)
3'-CCUUAUUUGAACUAAUAUAACAAAAAA-5'(SEQ ID NO:592)
KRAS-3708靶:5'-GGAATAAACTTGATTATATTGTTTTTT-3'(SEQ ID NO:1998)
5'-AUAAACUUGAUUAUAUUGUUUUUUU-3'(SEQ ID NO:5594)
3'-CUUAUUUGAACUAAUAUAACAAAAAAA-5'(SEQ ID NO:593)
KRAS-3709靶:5'-GAATAAACTTGATTATATTGTTTTTTT-3'(SEQ ID NO:1999)
5'-CUUGAUUAUAUUGUUUUUUUAUUUG-3'(SEQ ID NO:5595)
3'-UUGAACUAAUAUAACAAAAAAAUAAAC-5'(SEQ ID NO:594)
KRAS-3714靶:5'-AACTTGATTATATTGTTTTTTTATTTG-3'(SEQ ID NO:2000)
5'-UUGAUUAUAUUGUUUUUUUAUUUGG-3'(SEQ ID NO:5596)
3'-UGAACUAAUAUAACAAAAAAAUAAACC-5'(SEQ ID NO:595)
KRAS-3715靶:5'-ACTTGATTATATTGTTTTTTTATTTGG-3'(SEQ ID NO:2001)
5'-AUUAUAUUGUUUUUUUAUUUGGCAU-3'(SEQ ID NO:5597)
3'-ACUAAUAUAACAAAAAAAUAAACCGUA-5'(SEQ ID NO:596)
KRAS-3718靶:5'-TGATTATATTGTTTTTTTATTTGGCAT-3'(SEQ ID NO:2002)
5'-AUUGUUUUUUUAUUUGGCAUAACUG-3'(SEQ ID NO:5598)
3'-UAUAACAAAAAAAUAAACCGUAUUGAC-5'(SEQ ID NO:597)
KRAS-3723靶:5'-ATATTGTTTTTTTATTTGGCATAACTG-3'(SEQ ID NO:2003)
5'-UUGUUUUUUUAUUUGGCAUAACUGU-3'(SEQ ID NO:5599)
3'-AUAACAAAAAAAUAAACCGUAUUGACA-5'(SEQ ID NO:598)
KRAS-3724靶:5'-TATTGTTTTTTTATTTGGCATAACTGT-3'(SEQ ID NO:2004)
5'-UUUUUUAUUUGGCAUAACUGUGAUU-3'(SEQ ID NO:5600)
3'-CAAAAAAAUAAACCGUAUUGACACUAA-5'(SEQ ID NO:599)
KRAS-3728靶:5'-GTTTTTTTATTTGGCATAACTGTGATT-3'(SEQ ID NO:2005)
5'-UUUUUAUUUGGCAUAACUGUGAUUC-3'(SEQ ID NO:5601)
3'-AAAAAAAUAAACCGUAUUGACACUAAG-5'(SEQ ID NO:600)
KRAS-3729靶:5'-TTTTTTTATTTGGCATAACTGTGATTC-3'(SEQ ID NO:2006)
5'-AUAACUGUGAUUCUUUUAGGACAAU-3'(SEQ ID NO:5602)
3'-CGUAUUGACACUAAGAAAAUCCUGUUA-5'(SEQ ID NO:601)
KRAS-3741靶:5'-GCATAACTGTGATTCTTTTAGGACAAT-3'(SEQ ID NO:2007)
5'-UGUGAUUCUUUUAGGACAAUUACUG-3'(SEQ ID NO:5603)
3'-UGACACUAAGAAAAUCCUGUUAAUGAC-5'(SEQ ID NO:602)
KRAS-3746靶:5'-ACTGTGATTCTTTTAGGACAATTACTG-3'(SEQ ID NO:2008)
5'-GUGAUUCUUUUAGGACAAUUACUGU-3'(SEQ ID NO:5604)
3'-GACACUAAGAAAAUCCUGUUAAUGACA-5'(SEQ ID NO:603)
KRAS-3747靶:5'-CTGTGATTCTTTTAGGACAATTACTGT-3'(SEQ ID NO:2009)
5'-UGUAUGUCAGAUAUUCAUAUUGACC-3'(SEQ ID NO:5605)
3'-CCACAUACAGUCUAUAAGUAUAACUGG-5'(SEQ ID NO:604)
KRAS-3783靶:5'-GGTGTATGTCAGATATTCATATTGACC-3'(SEQ ID NO:2010)
5'-GUAUGUCAGAUAUUCAUAUUGACCC-3'(SEQ ID NO:5606)
3'-CACAUACAGUCUAUAAGUAUAACUGGG-5'(SEQ ID NO:605)
KRAS-3784靶:5'-GTGTATGTCAGATATTCATATTGACCC-3'(SEQ ID NO:2011)
5'-AAUGUGUAAUAUUCCAGUUUUCUCU-3'(SEQ ID NO:5607)
3'-GUUUACACAUUAUAAGGUCAAAAGAGA-5'(SEQ ID NO:606)
KRAS-3810靶:5'-CAAATGTGTAATATTCCAGTTTTCTCT-3'(SEQ ID NO:2012)
5'-UAAGUAAUUAAAAUAUACUUAAAAA-3'(SEQ ID NO:5608)
3'-GUAUUCAUUAAUUUUAUAUGAAUUUUU-5'(SEQ ID NO:607)
KRAS-3838靶:5'-CATAAGTAATTAAAATATACTTAAAAA-3'(SEQ ID NO:2013)
5'-AAGUAAUUAAAAUAUACUUAAAAAU-3'(SEQ ID NO:5609)
3'-UAUUCAUUAAUUUUAUAUGAAUUUUUA-5'(SEQ ID NO:608)
KRAS-3839靶:5'-ATAAGTAATTAAAATATACTTAAAAAT-3'(SEQ ID NO:2014)
5'-AGUAAUUAAAAUAUACUUAAAAAUU-3'(SEQ ID NO:5610)
3'-AUUCAUUAAUUUUAUAUGAAUUUUUAA-5'(SEQ ID NO:609)
KRAS-3840靶:5'-TAAGTAATTAAAATATACTTAAAAATT-3'(SEQ ID NO:2015)
5'-GUAAUUAAAAUAUACUUAAAAAUUA-3'(SEQ ID NO:5611)
3'-UUCAUUAAUUUUAUAUGAAUUUUUAAU-5'(SEQ ID NO:610)
KRAS-3841靶:5'-AAGTAATTAAAATATACTTAAAAATTA-3'(SEQ ID NO:2016)
5'-UAAUUAAAAUAUACUUAAAAAUUAA-3'(SEQ ID NO:5612)
3'-UCAUUAAUUUUAUAUGAAUUUUUAAUU-5'(SEQ ID NO:611)
KRAS-3842靶:5'-AGTAATTAAAATATACTTAAAAATTAA-3'(SEQ ID NO:2017)
5'-AAUUAAAAUAUACUUAAAAAUUAAU-3'(SEQ ID NO:5613)
3'-CAUUAAUUUUAUAUGAAUUUUUAAUUA-5'(SEQ ID NO:612)
KRAS-3843靶:5'-GTAATTAAAATATACTTAAAAATTAAT-3'(SEQ ID NO:2018)
5'-AUUAAAAUAUACUUAAAAAUUAAUA-3'(SEQ ID NO:5614)
3'-AUUAAUUUUAUAUGAAUUUUUAAUUAU-5'(SEQ ID NO:613)
KRAS-3844靶:5'-TAATTAAAATATACTTAAAAATTAATA-3'(SEQ ID NO:2019)
5'-UUAAAAUAUACUUAAAAAUUAAUAG-3'(SEQ ID NO:5615)
3'-UUAAUUUUAUAUGAAUUUUUAAUUAUC-5'(SEQ ID NO:614)
KRAS-3845靶:5'-AATTAAAATATACTTAAAAATTAATAG-3'(SEQ ID NO:2020)
5'-UAAAAUAUACUUAAAAAUUAAUAGU-3'(SEQ ID NO:5616)
3'-UAAUUUUAUAUGAAUUUUUAAUUAUCA-5'(SEQ ID NO:615)
KRAS-3846靶:5'-ATTAAAATATACTTAAAAATTAATAGT-3'(SEQ ID NO:2021)
5'-AAAUAUACUUAAAAAUUAAUAGUUU-3'(SEQ ID NO:5617)
3'-AUUUUAUAUGAAUUUUUAAUUAUCAAA-5'(SEQ ID NO:616)
KRAS-3848靶:5'-TAAAATATACTTAAAAATTAATAGTTT-3'(SEQ ID NO:2022)
5'-AAUAUACUUAAAAAUUAAUAGUUUU-3'(SEQ ID NO:5618)
3'-UUUUAUAUGAAUUUUUAAUUAUCAAAA-5'(SEQ ID NO:617)
KRAS-3849靶:5'-AAAATATACTTAAAAATTAATAGTTTT-3'(SEQ ID NO:2023)
5'-AUAUACUUAAAAAUUAAUAGUUUUA-3'(SEQ ID NO:5619)
3'-UUUAUAUGAAUUUUUAAUUAUCAAAAU-5'(SEQ ID NO:618)
KRAS-3850靶:5'-AAATATACTTAAAAATTAATAGTTTTA-3'(SEQ ID NO:2024)
5'-UAUACUUAAAAAUUAAUAGUUUUAU-3'(SEQ ID NO:5620)
3'-UUAUAUGAAUUUUUAAUUAUCAAAAUA-5'(SEQ ID NO:619)
KRAS-3851靶:5'-AATATACTTAAAAATTAATAGTTTTAT-3'(SEQ ID NO:2025)
5'-CUUAAAAAUUAAUAGUUUUAUCUGG-3'(SEQ ID NO:5621)
3'-AUGAAUUUUUAAUUAUCAAAAUAGACC-5'(SEQ ID NO:620)
KRAS-3855靶:5'-TACTTAAAAATTAATAGTTTTATCTGG-3'(SEQ ID NO:2026)
5'-AAAAUUAAUAGUUUUAUCUGGGUAC-3'(SEQ ID NO:5622)
3'-AUUUUUAAUUAUCAAAAUAGACCCAUG-5'(SEQ ID NO:621)
KRAS-3859靶:5'-TAAAAATTAATAGTTTTATCTGGGTAC-3'(SEQ ID NO:2027)
5'-AAAUUAAUAGUUUUAUCUGGGUACA-3'(SEQ ID NO:5623)
3'-UUUUUAAUUAUCAAAAUAGACCCAUGU-5'(SEQ ID NO:622)
KRAS-3860靶:5'-AAAAATTAATAGTTTTATCTGGGTACA-3'(SEQ ID NO:2028)
5'-AAUUAAUAGUUUUAUCUGGGUACAA-3'(SEQ ID NO:5624)
3'-UUUUAAUUAUCAAAAUAGACCCAUGUU-5'(SEQ ID NO:623)
KRAS-3861靶:5'-AAAATTAATAGTTTTATCTGGGTACAA-3'(SEQ ID NO:2029)
5'-CUGGGUACAAAUAAACAGGUGCCUG-3'(SEQ ID NO:5625)
3'-UAGACCCAUGUUUAUUUGUCCACGGAC-5'(SEQ ID NO:624)
KRAS-3876靶:5'-ATCTGGGTACAAATAAACAGGTGCCTG-3'(SEQ ID NO:2030)
5'-CAAGGAAACUUCUAUGUAAAAAUCA-3'(SEQ ID NO:5626)
3'-CUGUUCCUUUGAAGAUACAUUUUUAGU-5'(SEQ ID NO:625)
KRAS-3915靶:5'-GACAAGGAAACTTCTATGTAAAAATCA-3'(SEQ ID NO:2031)
5'-AAGGAAACUUCUAUGUAAAAAUCAC-3'(SEQ ID NO:5627)
3'-UGUUCCUUUGAAGAUACAUUUUUAGUG-5'(SEQ ID NO:626)
KRAS-3916靶:5'-ACAAGGAAACTTCTATGTAAAAATCAC-3'(SEQ ID NO:2032)
5'-AGGAAACUUCUAUGUAAAAAUCACU-3'(SEQ ID NO:5628)
3'-GUUCCUUUGAAGAUACAUUUUUAGUGA-5'(SEQ ID NO:627)
KRAS-3917靶:5'-CAAGGAAACTTCTATGTAAAAATCACT-3'(SEQ ID NO:2033)
5'-CUAUGUAAAAAUCACUAUGAUUUCU-3'(SEQ ID NO:5629)
3'-AAGAUACAUUUUUAGUGAUACUAAAGA-5'(SEQ ID NO:628)
KRAS-3926靶:5'-TTCTATGTAAAAATCACTATGATTTCT-3'(SEQ ID NO:2034)
5'-UAUGUAAAAAUCACUAUGAUUUCUG-3'(SEQ ID NO:5630)
3'-AGAUACAUUUUUAGUGAUACUAAAGAC-5'(SEQ ID NO:629)
KRAS-3927靶:5'-TCTATGTAAAAATCACTATGATTTCTG-3'(SEQ ID NO:2035)
5'-AUGUAAAAAUCACUAUGAUUUCUGA-3'(SEQ ID NO:5631)
3'-GAUACAUUUUUAGUGAUACUAAAGACU-5'(SEQ ID NO:630)
KRAS-3928靶:5'-CTATGTAAAAATCACTATGATTTCTGA-3'(SEQ ID NO:2036)
5'-AAAAAUCACUAUGAUUUCUGAAUUG-3'(SEQ ID NO:5632)
3'-CAUUUUUAGUGAUACUAAAGACUUAAC-5'(SEQ ID NO:631)
KRAS-3932靶:5'-GTAAAAATCACTATGATTTCTGAATTG-3'(SEQ ID NO:2037)
5'-AAAAUCACUAUGAUUUCUGAAUUGC-3'(SEQ ID NO:5633)
3'-AUUUUUAGUGAUACUAAAGACUUAACG-5'(SEQ ID NO:632)
KRAS-3933靶:5'-TAAAAATCACTATGATTTCTGAATTGC-3'(SEQ ID NO:2038)
5'-AUGAUUUCUGAAUUGCUAUGUGAAA-3'(SEQ ID NO:5634)
3'-GAUACUAAAGACUUAACGAUACACUUU-5'(SEQ ID NO:633)
KRAS-3942靶:5'-CTATGATTTCTGAATTGCTATGTGAAA-3'(SEQ ID NO:2039)
5'-UGAUUUCUGAAUUGCUAUGUGAAAC-3'(SEQ ID NO:5635)
3'-AUACUAAAGACUUAACGAUACACUUUG-5'(SEQ ID NO:634)
KRAS-3943靶:5'-TATGATTTCTGAATTGCTATGTGAAAC-3'(SEQ ID NO:2040)
5'-UGUGAAACUACAGAUCUUUGGAACA-3'(SEQ ID NO:5636)
3'-AUACACUUUGAUGUCUAGAAACCUUGU-5'(SEQ ID NO:635)
KRAS-3960靶:5'-TATGTGAAACTACAGATCTTTGGAACA-3'(SEQ ID NO:2041)
5'-GUGAAACUACAGAUCUUUGGAACAC-3'(SEQ ID NO:5637)
3'-UACACUUUGAUGUCUAGAAACCUUGUG-5'(SEQ ID NO:636)
KRAS-3961靶:5'-ATGTGAAACTACAGATCTTTGGAACAC-3'(SEQ ID NO:2042)
5'-GGUGUUAAGACUUACACAGUACCUC-3'(SEQ ID NO:5638)
3'-UCCCACAAUUCUGAAUGUGUCAUGGAG-5'(SEQ ID NO:637)
KRAS-3997靶:5'-AGGGTGTTAAGACTTACACAGTACCTC-3'(SEQ ID NO:2043)
5'-UAGGCCUCUUGAAUUUUUGAUGUAG-3'(SEQ ID NO:5639)
3'-AAAUCCGGAGAACUUAAAAACUACAUC-5'(SEQ ID NO:638)
KRAS-4084靶:5'-TTTAGGCCTCTTGAATTTTTGATGTAG-3'(SEQ ID NO:2044)
5'-UUGAAUUUUUGAUGUAGAUGGGCAU-3'(SEQ ID NO:5640)
3'-AGAACUUAAAAACUACAUCUACCCGUA-5'(SEQ ID NO:639)
KRAS-4092靶:5'-TCTTGAATTTTTGATGTAGATGGGCAT-3'(SEQ ID NO:2045)
5'-UGAAUUUUUGAUGUAGAUGGGCAUU-3'(SEQ ID NO:5641)
3'-GAACUUAAAAACUACAUCUACCCGUAA-5'(SEQ ID NO:640)
KRAS-4093靶:5'-CTTGAATTTTTGATGTAGATGGGCATT-3'(SEQ ID NO:2046)
5'-GAUGGGCAUUUUUUUAAGGUAGUGG-3'(SEQ ID NO:5642)
3'-AUCUACCCGUAAAAAAAUUCCAUCACC-5'(SEQ ID NO:641)
KRAS-4108靶:5'-TAGATGGGCATTTTTTTAAGGTAGTGG-3'(SEQ ID NO:2047)
5'-CAUUUUUUUAAGGUAGUGGUUAAUU-3'(SEQ ID NO:5643)
3'-CCGUAAAAAAAUUCCAUCACCAAUUAA-5'(SEQ ID NO:642)
KRAS-4114靶:5'-GGCATTTTTTTAAGGTAGTGGTTAATT-3'(SEQ ID NO:2048)
5'-GUAGUGGUUAAUUACCUUUAUGUGA-3'(SEQ ID NO:5644)
3'-UCCAUCACCAAUUAAUGGAAAUACACU-5'(SEQ ID NO:643)
KRAS-4126靶:5'-AGGTAGTGGTTAATTACCTTTATGTGA-3'(SEQ ID NO:2049)
5'-AGUGGUUAAUUACCUUUAUGUGAAC-3'(SEQ ID NO:5645)
3'-CAUCACCAAUUAAUGGAAAUACACUUG-5'(SEQ ID NO:644)
KRAS-4128靶:5'-GTAGTGGTTAATTACCTTTATGTGAAC-3'(SEQ ID NO:2050)
5'-GUGGUUAAUUACCUUUAUGUGAACU-3'(SEQ ID NO:5646)
3'-AUCACCAAUUAAUGGAAAUACACUUGA-5'(SEQ ID NO:645)
KRAS-4129靶:5'-TAGTGGTTAATTACCTTTATGTGAACT-3'(SEQ ID NO:2051)
5'-UGGUUAAUUACCUUUAUGUGAACUU-3'(SEQ ID NO:5647)
3'-UCACCAAUUAAUGGAAAUACACUUGAA-5'(SEQ ID NO:646)
KRAS-4130靶:5'-AGTGGTTAATTACCTTTATGTGAACTT-3'(SEQ ID NO:2052)
5'-GGUUAAUUACCUUUAUGUGAACUUU-3'(SEQ ID NO:5648)
3'-CACCAAUUAAUGGAAAUACACUUGAAA-5'(SEQ ID NO:647)
KRAS-4131靶:5'-GTGGTTAATTACCTTTATGTGAACTTT-3'(SEQ ID NO:2053)
5'-CUUUAUGUGAACUUUGAAUGGUUUA-3'(SEQ ID NO:5649)
3'-UGGAAAUACACUUGAAACUUACCAAAU-5'(SEQ ID NO:648)
KRAS-4141靶:5'-ACCTTTATGTGAACTTTGAATGGTTTA-3'(SEQ ID NO:2054)
5'-UGUGAACUUUGAAUGGUUUAACAAA-3'(SEQ ID NO:5650)
3'-AUACACUUGAAACUUACCAAAUUGUUU-5'(SEQ ID NO:649)
KRAS-4146靶:5'-TATGTGAACTTTGAATGGTTTAACAAA-3'(SEQ ID NO:2055)
5'-CUUUGAAUGGUUUAACAAAAGAUUU-3'(SEQ ID NO:5651)
3'-UUGAAACUUACCAAAUUGUUUUCUAAA-5'(SEQ ID NO:650)
KRAS-4152靶:5'-AACTTTGAATGGTTTAACAAAAGATTT-3'(SEQ ID NO:2056)
5'-GAAUGGUUUAACAAAAGAUUUGUUU-3'(SEQ ID NO:5652)
3'-AACUUACCAAAUUGUUUUCUAAACAAA-5'(SEQ ID NO:651)
KRAS-4156靶:5'-TTGAATGGTTTAACAAAAGATTTGTTT-3'(SEQ ID NO:2057)
5'-AAUGGUUUAACAAAAGAUUUGUUUU-3'(SEQ ID NO:5653)
3'-ACUUACCAAAUUGUUUUCUAAACAAAA-5'(SEQ ID NO:652)
KRAS-4157靶:5'-TGAATGGTTTAACAAAAGATTTGTTTT-3'(SEQ ID NO:2058)
5'-AUGGUUUAACAAAAGAUUUGUUUUU-3'(SEQ ID NO:5654)
3'-CUUACCAAAUUGUUUUCUAAACAAAAA-5'(SEQ ID NO:653)
KRAS-4158靶:5'-GAATGGTTTAACAAAAGATTTGTTTTT-3'(SEQ ID NO:2059)
5'-UGGUUUAACAAAAGAUUUGUUUUUG-3'(SEQ ID NO:5655)
3'-UUACCAAAUUGUUUUCUAAACAAAAAC-5'(SEQ ID NO:654)
KRAS-4159靶:5'-AATGGTTTAACAAAAGATTTGTTTTTG-3'(SEQ ID NO:2060)
5'-GGUUUAACAAAAGAUUUGUUUUUGU-3'(SEQ ID NO:5656)
3'-UACCAAAUUGUUUUCUAAACAAAAACA-5'(SEQ ID NO:655)
KRAS-4160靶:5'-ATGGTTTAACAAAAGATTTGTTTTTGT-3'(SEQ ID NO:2061)
5'-UUUAACAAAAGAUUUGUUUUUGUAG-3'(SEQ ID NO:5657)
3'-CCAAAUUGUUUUCUAAACAAAAACAUC-5'(SEQ ID NO:656)
KRAS-4162靶:5'-GGTTTAACAAAAGATTTGTTTTTGTAG-3'(SEQ ID NO:2062)
5'-UUAACAAAAGAUUUGUUUUUGUAGA-3'(SEQ ID NO:5658)
3'-CAAAUUGUUUUCUAAACAAAAACAUCU-5'(SEQ ID NO:657)
KRAS-4163靶:5'-GTTTAACAAAAGATTTGTTTTTGTAGA-3'(SEQ ID NO:2063)
5'-CAAAAGAUUUGUUUUUGUAGAGAUU-3'(SEQ ID NO:5659)
3'-UUGUUUUCUAAACAAAAACAUCUCUAA-5'(SEQ ID NO:658)
KRAS-4167靶:5'-AACAAAAGATTTGTTTTTGTAGAGATT-3'(SEQ ID NO:2064)
5'-AAAAGAUUUGUUUUUGUAGAGAUUU-3'(SEQ ID NO:5660)
3'-UGUUUUCUAAACAAAAACAUCUCUAAA-5'(SEQ ID NO:659)
KRAS-4168靶:5'-ACAAAAGATTTGTTTTTGTAGAGATTT-3'(SEQ ID NO:2065)
5'-AAAGAUUUGUUUUUGUAGAGAUUUU-3'(SEQ ID NO:5661)
3'-GUUUUCUAAACAAAAACAUCUCUAAAA-5'(SEQ ID NO:660)
KRAS-4169靶:5'-CAAAAGATTTGTTTTTGTAGAGATTTT-3'(SEQ ID NO:2066)
5'-AGAUUUGUUUUUGUAGAGAUUUUAA-3'(SEQ ID NO:5662)
3'-UUUCUAAACAAAAACAUCUCUAAAAUU-5'(SEQ ID NO:661)
KRAS-4171靶:5'-AAAGATTTGTTTTTGTAGAGATTTTAA-3'(SEQ ID NO:2067)
5'-GAUUUGUUUUUGUAGAGAUUUUAAA-3'(SEQ ID NO:5663)
3'-UUCUAAACAAAAACAUCUCUAAAAUUU-5'(SEQ ID NO:662)
KRAS-4172靶:5'-AAGATTTGTTTTTGTAGAGATTTTAAA-3'(SEQ ID NO:2068)
5'-AUUUGUUUUUGUAGAGAUUUUAAAG-3'(SEQ ID NO:5664)
3'-UCUAAACAAAAACAUCUCUAAAAUUUC-5'(SEQ ID NO:663)
KRAS-4173靶:5'-AGATTTGTTTTTGTAGAGATTTTAAAG-3'(SEQ ID NO:2069)
5'-UUUGUUUUUGUAGAGAUUUUAAAGG-3'(SEQ ID NO:5665)
3'-CUAAACAAAAACAUCUCUAAAAUUUCC-5'(SEQ ID NO:664)
KRAS-4174靶:5'-GATTTGTTTTTGTAGAGATTTTAAAGG-3'(SEQ ID NO:2070)
5'-UUUGUAGAGAUUUUAAAGGGGGAGA-3'(SEQ ID NO:5666)
3'-AAAAACAUCUCUAAAAUUUCCCCCUCU-5'(SEQ ID NO:665)
KRAS-4180靶:5'-TTTTTGTAGAGATTTTAAAGGGGGAGA-3'(SEQ ID NO:2071)
5'-GGGGGAGAAUUCUAGAAAUAAAUGU-3'(SEQ ID NO:5667)
3'-UUCCCCCUCUUAAGAUCUUUAUUUACA-5'(SEQ ID NO:666)
KRAS-4197靶:5'-AAGGGGGAGAATTCTAGAAATAAATGT-3'(SEQ ID NO:2072)
5'-GGGAGAAUUCUAGAAAUAAAUGUUA-3'(SEQ ID NO:5668)
3'-CCCCCUCUUAAGAUCUUUAUUUACAAU-5'(SEQ ID NO:667)
KRAS-4199靶:5'-GGGGGAGAATTCTAGAAATAAATGTTA-3'(SEQ ID NO:2073)
5'-GGAGAAUUCUAGAAAUAAAUGUUAC-3'(SEQ ID NO:5669)
3'-CCCCUCUUAAGAUCUUUAUUUACAAUG-5'(SEQ ID NO:668)
KRAS-4200靶:5'-GGGGAGAATTCTAGAAATAAATGTTAC-3'(SEQ ID NO:2074)
5'-GAGAAUUCUAGAAAUAAAUGUUACC-3'(SEQ ID NO:5670)
3'-CCCUCUUAAGAUCUUUAUUUACAAUGG-5'(SEQ ID NO:669)
KRAS-4201靶:5'-GGGAGAATTCTAGAAATAAATGTTACC-3'(SEQ ID NO:2075)
5'-AGAAUUCUAGAAAUAAAUGUUACCU-3'(SEQ ID NO:5671)
3'-CCUCUUAAGAUCUUUAUUUACAAUGGA-5'(SEQ ID NO:670)
KRAS-4202靶:5'-GGAGAATTCTAGAAATAAATGTTACCT-3'(SEQ ID NO:2076)
5'-GAAUUCUAGAAAUAAAUGUUACCUA-3'(SEQ ID NO:5672)
3'-CUCUUAAGAUCUUUAUUUACAAUGGAU-5'(SEQ ID NO:671)
KRAS-4203靶:5'-GAGAATTCTAGAAATAAATGTTACCTA-3'(SEQ ID NO:2077)
5'-CUAGAAAUAAAUGUUACCUAAUUAU-3'(SEQ ID NO:5673)
3'-AAGAUCUUUAUUUACAAUGGAUUAAUA-5'(SEQ ID NO:672)
KRAS-4208靶:5'-TTCTAGAAATAAATGTTACCTAATTAT-3'(SEQ ID NO:2078)
5'-UAGAAAUAAAUGUUACCUAAUUAUU-3'(SEQ ID NO:5674)
3'-AGAUCUUUAUUUACAAUGGAUUAAUAA-5'(SEQ ID NO:673)
KRAS-4209靶:5'-TCTAGAAATAAATGTTACCTAATTATT-3'(SEQ ID NO:2079)
5'-AGAAAUAAAUGUUACCUAAUUAUUA-3'(SEQ ID NO:5675)
3'-GAUCUUUAUUUACAAUGGAUUAAUAAU-5'(SEQ ID NO:674)
KRAS-4210靶:5'-CTAGAAATAAATGTTACCTAATTATTA-3'(SEQ ID NO:2080)
5'-GAAAUAAAUGUUACCUAAUUAUUAC-3'(SEQ ID NO:5676)
3'-AUCUUUAUUUACAAUGGAUUAAUAAUG-5'(SEQ ID NO:675)
KRAS-4211靶:5'-TAGAAATAAATGTTACCTAATTATTAC-3'(SEQ ID NO:2081)
5'-AAAUAAAUGUUACCUAAUUAUUACA-3'(SEQ ID NO:5677)
3'-UCUUUAUUUACAAUGGAUUAAUAAUGU-5'(SEQ ID NO:676)
KRAS-4212靶:5'-AGAAATAAATGTTACCTAATTATTACA-3'(SEQ ID NO:2082)
5'-AUAAAUGUUACCUAAUUAUUACAGC-3'(SEQ ID NO:5678)
3'-UUUAUUUACAAUGGAUUAAUAAUGUCG-5'(SEQ ID NO:677)
KRAS-4214靶:5'-AAATAAATGTTACCTAATTATTACAGC-3'(SEQ ID NO:2083)
5'-CUAAUUAUUACAGCCUUAAAGACAA-3'(SEQ ID NO:5679)
3'-UGGAUUAAUAAUGUCGGAAUUUCUGUU-5'(SEQ ID NO:678)
KRAS-4225靶:5'-ACCTAATTATTACAGCCTTAAAGACAA-3'(SEQ ID NO:2084)
5'-UAAUUAUUACAGCCUUAAAGACAAA-3'(SEQ ID NO:5680)
3'-GGAUUAAUAAUGUCGGAAUUUCUGUUU-5'(SEQ ID NO:679)
KRAS-4226靶:5'-CCTAATTATTACAGCCTTAAAGACAAA-3'(SEQ ID NO:2085)
5'-UUAAAGACAAAAAUCCUUGUUGAAG-3'(SEQ ID NO:5681)
3'-GGAAUUUCUGUUUUUAGGAACAACUUC-5'(SEQ ID NO:680)
KRAS-4240靶:5'-CCTTAAAGACAAAAATCCTTGTTGAAG-3'(SEQ ID NO:2086)
5'-AAGACAAAAAUCCUUGUUGAAGUUU-3'(SEQ ID NO:5682)
3'-AUUUCUGUUUUUAGGAACAACUUCAAA-5'(SEQ ID NO:681)
KRAS-4243靶:5'-TAAAGACAAAAATCCTTGTTGAAGTTT-3'(SEQ ID NO:2087)
5'-CUUGUUGAAGUUUUUUUAAAAAAAG-3'(SEQ ID NO:5683)
3'-AGGAACAACUUCAAAAAAAUUUUUUUC-5'(SEQ ID NO:682)
KRAS-4255靶:5'-TCCTTGTTGAAGTTTTTTTAAAAAAAG-3'(SEQ ID NO:2088)
5'-UUGUUGAAGUUUUUUUAAAAAAAGC-3'(SEQ ID NO:5684)
3'-GGAACAACUUCAAAAAAAUUUUUUUCG-5'(SEQ ID NO:683)
KRAS-4256靶:5'-CCTTGTTGAAGTTTTTTTAAAAAAAGC-3'(SEQ ID NO:2089)
5'-GUUGAAGUUUUUUUAAAAAAAGCUA-3'(SEQ ID NO:5685)
3'-AACAACUUCAAAAAAAUUUUUUUCGAU-5'(SEQ ID NO:684)
KRAS-4258靶:5'-TTGTTGAAGTTTTTTTAAAAAAAGCTA-3'(SEQ ID NO:2090)
5'-UUGAAGUUUUUUUAAAAAAAGCUAA-3'(SEQ ID NO:5686)
3'-ACAACUUCAAAAAAAUUUUUUUCGAUU-5'(SEQ ID NO:685)
KRAS-4259靶:5'-TGTTGAAGTTTTTTTAAAAAAAGCTAA-3'(SEQ ID NO:2091)
5'-AGUUUUUUUAAAAAAAGCUAAAUUA-3'(SEQ ID NO:5687)
3'-CUUCAAAAAAAUUUUUUUCGAUUUAAU-5'(SEQ ID NO:686)
KRAS-4263靶:5'-GAAGTTTTTTTAAAAAAAGCTAAATTA-3'(SEQ ID NO:2092)
5'-GUUUUUUUAAAAAAAGCUAAAUUAC-3'(SEQ ID NO:5688)
3'-UUCAAAAAAAUUUUUUUCGAUUUAAUG-5'(SEQ ID NO:687)
KRAS-4264靶:5'-AAGTTTTTTTAAAAAAAGCTAAATTAC-3'(SEQ ID NO:2093)
5'-UUUUUUUAAAAAAAGCUAAAUUACA-3'(SEQ ID NO:5689)
3'-UCAAAAAAAUUUUUUUCGAUUUAAUGU-5'(SEQ ID NO:688)
KRAS-4265靶:5'-AGTTTTTTTAAAAAAAGCTAAATTACA-3'(SEQ ID NO:2094)
5'-UUUUUUAAAAAAAGCUAAAUUACAU-3'(SEQ ID NO:5690)
3'-CAAAAAAAUUUUUUUCGAUUUAAUGUA-5'(SEQ ID NO:689)
KRAS-4266靶:5'-GTTTTTTTAAAAAAAGCTAAATTACAT-3'(SEQ ID NO:2095)
5'-UUUUUAAAAAAAGCUAAAUUACAUA-3'(SEQ ID NO:5691)
3'-AAAAAAAUUUUUUUCGAUUUAAUGUAU-5'(SEQ ID NO:690)
KRAS-4267靶:5'-TTTTTTTAAAAAAAGCTAAATTACATA-3'(SEQ ID NO:2096)
5'-UAAAAAAAGCUAAAUUACAUAGACU-3'(SEQ ID NO:5692)
3'-AAAUUUUUUUCGAUUUAAUGUAUCUGA-5'(SEQ ID NO:691)
KRAS-4271靶:5'-TTTAAAAAAAGCTAAATTACATAGACT-3'(SEQ ID NO:2097)
5'-AAAAAAGCUAAAUUACAUAGACUUA-3'(SEQ ID NO:5693)
3'-AUUUUUUUCGAUUUAAUGUAUCUGAAU-5'(SEQ ID NO:692)
KRAS-4273靶:5'-TAAAAAAAGCTAAATTACATAGACTTA-3'(SEQ ID NO:2098)
5'-UUAGGCAUUAACAUGUUUGUGGAAG-3'(SEQ ID NO:5694)
3'-UGAAUCCGUAAUUGUACAAACACCUUC-5'(SEQ ID NO:693)
KRAS-4295靶:5'-ACTTAGGCATTAACATGTTTGTGGAAG-3'(SEQ ID NO:2099)
5'-UAGGCAUUAACAUGUUUGUGGAAGA-3'(SEQ ID NO:5695)
3'-GAAUCCGUAAUUGUACAAACACCUUCU-5'(SEQ ID NO:694)
KRAS-4296靶:5'-CTTAGGCATTAACATGTTTGTGGAAGA-3'(SEQ ID NO:2100)
5'-CAGACGUAUAUUGUAUCAUUUGAGU-3'(SEQ ID NO:5696)
3'-UCGUCUGCAUAUAACAUAGUAAACUCA-5'(SEQ ID NO:695)
KRAS-4327靶:5'-AGCAGACGTATATTGTATCATTTGAGT-3'(SEQ ID NO:2101)
5'-CGUAUAUUGUAUCAUUUGAGUGAAU-3'(SEQ ID NO:5697)
3'-CUGCAUAUAACAUAGUAAACUCACUUA-5'(SEQ ID NO:696)
KRAS-4331靶:5'-GACGTATATTGTATCATTTGAGTGAAT-3'(SEQ ID NO:2102)
5'-UAUAUUGUAUCAUUUGAGUGAAUGU-3'(SEQ ID NO:5698)
3'-GCAUAUAACAUAGUAAACUCACUUACA-5'(SEQ ID NO:697)
KRAS-4333靶:5'-CGTATATTGTATCATTTGAGTGAATGT-3'(SEQ ID NO:2103)
5'-AUUGUAUCAUUUGAGUGAAUGUUCC-3'(SEQ ID NO:5699)
3'-UAUAACAUAGUAAACUCACUUACAAGG-5'(SEQ ID NO:698)
KRAS-4336靶:5'-ATATTGTATCATTTGAGTGAATGTTCC-3'(SEQ ID NO:2104)
5'-UUGUAUCAUUUGAGUGAAUGUUCCC-3'(SEQ ID NO:5700)
3'-AUAACAUAGUAAACUCACUUACAAGGG-5'(SEQ ID NO:699)
KRAS-4337靶:5'-TATTGTATCATTTGAGTGAATGTTCCC-3'(SEQ ID NO:2105)
5'-UGUAUCAUUUGAGUGAAUGUUCCCA-3'(SEQ ID NO:5701)
3'-UAACAUAGUAAACUCACUUACAAGGGU-5'(SEQ ID NO:700)
KRAS-4338靶:5'-ATTGTATCATTTGAGTGAATGTTCCCA-3'(SEQ ID NO:2106)
5'-AGGAAUUUAGAACCUAACUUUUAUA-3'(SEQ ID NO:5702)
3'-UAUCCUUAAAUCUUGGAUUGAAAAUAU-5'(SEQ ID NO:701)
KRAS-4404靶:5'-ATAGGAATTTAGAACCTAACTTTTATA-3'(SEQ ID NO:2107)
5'-GGAAUUUAGAACCUAACUUUUAUAG-3'(SEQ ID NO:5703)
3'-AUCCUUAAAUCUUGGAUUGAAAAUAUC-5'(SEQ ID NO:702)
KRAS-4405靶:5'-TAGGAATTTAGAACCTAACTTTTATAG-3'(SEQ ID NO:2108)
5'-UUUAGAACCUAACUUUUAUAGGUUA-3'(SEQ ID NO:5704)
3'-UUAAAUCUUGGAUUGAAAAUAUCCAAU-5'(SEQ ID NO:703)
KRAS-4409靶:5'-AATTTAGAACCTAACTTTTATAGGTTA-3'(SEQ ID NO:2109)
5'-UUAGAACCUAACUUUUAUAGGUUAU-3'(SEQ ID NO:5705)
3'-UAAAUCUUGGAUUGAAAAUAUCCAAUA-5'(SEQ ID NO:704)
KRAS-4410靶:5'-ATTTAGAACCTAACTTTTATAGGTTAT-3'(SEQ ID NO:2110)
5'-UAGAACCUAACUUUUAUAGGUUAUC-3'(SEQ ID NO:5706)
3'-AAAUCUUGGAUUGAAAAUAUCCAAUAG-5'(SEQ ID NO:705)
KRAS-4411靶:5'-TTTAGAACCTAACTTTTATAGGTTATC-3'(SEQ ID NO:2111)
5'-AGAACCUAACUUUUAUAGGUUAUCA-3'(SEQ ID NO:5707)
3'-AAUCUUGGAUUGAAAAUAUCCAAUAGU-5'(SEQ ID NO:706)
KRAS-4412靶:5'-TTAGAACCTAACTTTTATAGGTTATCA-3'(SEQ ID NO:2112)
5'-UUAUAGGUUAUCAAAACUGUUGUCA-3'(SEQ ID NO:5708)
3'-AAAAUAUCCAAUAGUUUUGACAACAGU-5'(SEQ ID NO:707)
KRAS-4424靶:5'-TTTTATAGGTTATCAAAACTGTTGTCA-3'(SEQ ID NO:2113)
5'-AUAGGUUAUCAAAACUGUUGUCACC-3'(SEQ ID NO:5709)
3'-AAUAUCCAAUAGUUUUGACAACAGUGG-5'(SEQ ID NO:708)
KRAS-4426靶:5'-TTATAGGTTATCAAAACTGTTGTCACC-3'(SEQ ID NO:2114)
5'-UUUUGUCCUAAUAUAUACAUAGAAA-3'(SEQ ID NO:5710)
3'-UUAAAACAGGAUUAUAUAUGUAUCUUU-5'(SEQ ID NO:709)
KRAS-4460靶:5'-AATTTTGTCCTAATATATACATAGAAA-3'(SEQ ID NO:2115)
5'-UUUGUCCUAAUAUAUACAUAGAAAC-3'(SEQ ID NO:5711)
3'-UAAAACAGGAUUAUAUAUGUAUCUUUG-5'(SEQ ID NO:710)
KRAS-4461靶:5'-ATTTTGTCCTAATATATACATAGAAAC-3'(SEQ ID NO:2116)
5'-UUGUCCUAAUAUAUACAUAGAAACU-3'(SEQ ID NO:5712)
3'-AAAACAGGAUUAUAUAUGUAUCUUUGA-5'(SEQ ID NO:711)
KRAS-4462靶:5'-TTTTGTCCTAATATATACATAGAAACT-3'(SEQ ID NO:2117)
5'-UAAUAUAUACAUAGAAACUUUGUGG-3'(SEQ ID NO:5713)
3'-GGAUUAUAUAUGUAUCUUUGAAACACC-5'(SEQ ID NO:712)
KRAS-4468靶:5'-CCTAATATATACATAGAAACTTTGTGG-3'(SEQ ID NO:2118)
5'-UAUACAUAGAAACUUUGUGGGGCAU-3'(SEQ ID NO:5714)
3'-AUAUAUGUAUCUUUGAAACACCCCGUA-5'(SEQ ID NO:713)
KRAS-4473靶:5'-TATATACATAGAAACTTTGTGGGGCAT-3'(SEQ ID NO:2119)
5'-CAAGUUCAUCUCAUUUGUAUUCCAU-3'(SEQ ID NO:5715)
3'-GUGUUCAAGUAGAGUAAACAUAAGGUA-5'(SEQ ID NO:714)
KRAS-4516靶:5'-CACAAGTTCATCTCATTTGTATTCCAT-3'(SEQ ID NO:2120)
5'-CAUUUGUAUUCCAUUGAUUUUUUUU-3'(SEQ ID NO:5716)
3'-GAGUAAACAUAAGGUAACUAAAAAAAA-5'(SEQ ID NO:715)
KRAS-4527靶:5'-CTCATTTGTATTCCATTGATTTTTTTT-3'(SEQ ID NO:2121)
5'-AUUUGUAUUCCAUUGAUUUUUUUUU-3'(SEQ ID NO:5717)
3'-AGUAAACAUAAGGUAACUAAAAAAAAA-5'(SEQ ID NO:716)
KRAS-4528靶:5'-TCATTTGTATTCCATTGATTTTTTTTT-3'(SEQ ID NO:2122)
5'-UUUGUAUUCCAUUGAUUUUUUUUUU-3'(SEQ ID NO:5718)
3'-GUAAACAUAAGGUAACUAAAAAAAAAA-5'(SEQ ID NO:717)
KRAS-4529靶:5'-CATTTGTATTCCATTGATTTTTTTTTT-3'(SEQ ID NO:2123)
5'-UUGUAUUCCAUUGAUUUUUUUUUUC-3'(SEQ ID NO:5719)
3'-UAAACAUAAGGUAACUAAAAAAAAAAG-5'(SEQ ID NO:718)
KRAS-4530靶:5'-ATTTGTATTCCATTGATTTTTTTTTTC-3'(SEQ ID NO:2124)
5'-UGUAUUCCAUUGAUUUUUUUUUUCU-3'(SEQ ID NO:5720)
3'-AAACAUAAGGUAACUAAAAAAAAAAGA-5'(SEQ ID NO:719)
KRAS-4531靶:5'-TTTGTATTCCATTGATTTTTTTTTTCT-3'(SEQ ID NO:2125)
5'-GUAUUCCAUUGAUUUUUUUUUUCUU-3'(SEQ ID NO:5721)
3'-AACAUAAGGUAACUAAAAAAAAAAGAA-5'(SEQ ID NO:720)
KRAS-4532靶:5'-TTGTATTCCATTGATTTTTTTTTTCTT-3'(SEQ ID NO:2126)
5'-UAUUCCAUUGAUUUUUUUUUUCUUC-3'(SEQ ID NO:5722)
3'-ACAUAAGGUAACUAAAAAAAAAAGAAG-5'(SEQ ID NO:721)
KRAS-4533靶:5'-TGTATTCCATTGATTTTTTTTTTCTTC-3'(SEQ ID NO:2127)
5'-UUGAUUUUUUUUUUCUUCUAAACAU-3'(SEQ ID NO:5723)
3'-GUAACUAAAAAAAAAAGAAGAUUUGUA-5'(SEQ ID NO:722)
KRAS-4540靶:5'-CATTGATTTTTTTTTTCTTCTAAACAT-3'(SEQ ID NO:2128)
5'-UGAUUUUUUUUUUCUUCUAAACAUU-3'(SEQ ID NO:5724)
3'-UAACUAAAAAAAAAAGAAGAUUUGUAA-5'(SEQ ID NO:723)
KRAS-4541靶:5'-ATTGATTTTTTTTTTCTTCTAAACATT-3'(SEQ ID NO:2129)
5'-UUUUUUUUUCUUCUAAACAUUUUUU-3'(SEQ ID NO:5725)
3'-UAAAAAAAAAAGAAGAUUUGUAAAAAA-5'(SEQ ID NO:724)
KRAS-4545靶:5'-ATTTTTTTTTTCTTCTAAACATTTTTT-3'(SEQ ID NO:2130)
5'-UUUUUUUUCUUCUAAACAUUUUUUC-3'(SEQ ID NO:5726)
3'-AAAAAAAAAAGAAGAUUUGUAAAAAAG-5'(SEQ ID NO:725)
KRAS-4546靶:5'-TTTTTTTTTTCTTCTAAACATTTTTTC-3'(SEQ ID NO:2131)
5'-UUUUUUUCUUCUAAACAUUUUUUCU-3'(SEQ ID NO:5727)
3'-AAAAAAAAAGAAGAUUUGUAAAAAAGA-5'(SEQ ID NO:726)
KRAS-4547靶:5'-TTTTTTTTTCTTCTAAACATTTTTTCT-3'(SEQ ID NO:2132)
5'-UUUUUUCUUCUAAACAUUUUUUCUU-3'(SEQ ID NO:5728)
3'-AAAAAAAAGAAGAUUUGUAAAAAAGAA-5'(SEQ ID NO:727)
KRAS-4548靶:5'-TTTTTTTTCTTCTAAACATTTTTTCTT-3'(SEQ ID NO:2133)
5'-UUUUUCUUCUAAACAUUUUUUCUUC-3'(SEQ ID NO:5729)
3'-AAAAAAAGAAGAUUUGUAAAAAAGAAG-5'(SEQ ID NO:728)
KRAS-4549靶:5'-TTTTTTTCTTCTAAACATTTTTTCTTC-3'(SEQ ID NO:2134)
5'-CAUUUUUUCUUCAAACAGUAUAUAA-3'(SEQ ID NO:5730)
3'-UUGUAAAAAAGAAGUUUGUCAUAUAUU-5'(SEQ ID NO:729)
KRAS-4562靶:5'-AACATTTTTTCTTCAAACAGTATATAA-3'(SEQ ID NO:2135)
5'-AUUUUUUCUUCAAACAGUAUAUAAC-3'(SEQ ID NO:5731)
3'-UGUAAAAAAGAAGUUUGUCAUAUAUUG-5'(SEQ ID NO:730)
KRAS-4563靶:5'-ACATTTTTTCTTCAAACAGTATATAAC-3'(SEQ ID NO:2136)
5'-UUUUUUCUUCAAACAGUAUAUAACU-3'(SEQ ID NO:5732)
3'-GUAAAAAAGAAGUUUGUCAUAUAUUGA-5'(SEQ ID NO:731)
KRAS-4564靶:5'-CATTTTTTCTTCAAACAGTATATAACT-3'(SEQ ID NO:2137)
5'-UUUUUCUUCAAACAGUAUAUAACUU-3'(SEQ ID NO:5733)
3'-UAAAAAAGAAGUUUGUCAUAUAUUGAA-5'(SEQ ID NO:732)
KRAS-4565靶:5'-ATTTTTTCTTCAAACAGTATATAACTT-3'(SEQ ID NO:2138)
5'-UUUUCUUCAAACAGUAUAUAACUUU-3'(SEQ ID NO:5734)
3'-AAAAAAGAAGUUUGUCAUAUAUUGAAA-5'(SEQ ID NO:733)
KRAS-4566靶:5'-TTTTTTCTTCAAACAGTATATAACTTT-3'(SEQ ID NO:2139)
5'-CAAACAGUAUAUAACUUUUUUUAGG-3'(SEQ ID NO:5735)
3'-AAGUUUGUCAUAUAUUGAAAAAAAUCC-5'(SEQ ID NO:734)
KRAS-4573靶:5'-TTCAAACAGTATATAACTTTTTTTAGG-3'(SEQ ID NO:2140)
5'-AGUAUAUAACUUUUUUUAGGGGAUU-3'(SEQ ID NO:5736)
3'-UGUCAUAUAUUGAAAAAAAUCCCCUAA-5'(SEQ ID NO:735)
KRAS-4578靶:5'-ACAGTATATAACTTTTTTTAGGGGATT-3'(SEQ ID NO:2141)
5'-GUAUAUAACUUUUUUUAGGGGAUUU-3'(SEQ ID NO:5737)
3'-GUCAUAUAUUGAAAAAAAUCCCCUAAA-5'(SEQ ID NO:736)
KRAS-4579靶:5'-CAGTATATAACTTTTTTTAGGGGATTT-3'(SEQ ID NO:2142)
5'-UAUAUAACUUUUUUUAGGGGAUUUU-3'(SEQ ID NO:5738)
3'-UCAUAUAUUGAAAAAAAUCCCCUAAAA-5'(SEQ ID NO:737)
KRAS-4580靶:5'-AGTATATAACTTTTTTTAGGGGATTTT-3'(SEQ ID NO:2143)
5'-AUAUAACUUUUUUUAGGGGAUUUUU-3'(SEQ ID NO:5739)
3'-CAUAUAUUGAAAAAAAUCCCCUAAAAA-5'(SEQ ID NO:738)
KRAS-4581靶:5'-GTATATAACTTTTTTTAGGGGATTTTT-3'(SEQ ID NO:2144)
5'-CUUUUUUUAGGGGAUUUUUUUUUAG-3'(SEQ ID NO:5740)
3'-UUGAAAAAAAUCCCCUAAAAAAAAAUC-5'(SEQ ID NO:739)
KRAS-4587靶:5'-AACTTTTTTTAGGGGATTTTTTTTTAG-3'(SEQ ID NO:2145)
5'-UUUUUUUAGGGGAUUUUUUUUUAGA-3'(SEQ ID NO:5741)
3'-UGAAAAAAAUCCCCUAAAAAAAAAUCU-5'(SEQ ID NO:740)
KRAS-4588靶:5'-ACTTTTTTTAGGGGATTTTTTTTTAGA-3'(SEQ ID NO:2146)
5'-GAUUUUUUUUUAGACAGCAAAAACU-3'(SEQ ID NO:5742)
3'-CCCUAAAAAAAAAUCUGUCGUUUUUGA-5'(SEQ ID NO:741)
KRAS-4599靶:5'-GGGATTTTTTTTTAGACAGCAAAAACT-3'(SEQ ID NO:2147)
5'-AUUUUUUUUUAGACAGCAAAAACUA-3'(SEQ ID NO:5743)
3'-CCUAAAAAAAAAUCUGUCGUUUUUGAU-5'(SEQ ID NO:742)
KRAS-4600靶:5'-GGATTTTTTTTTAGACAGCAAAAACTA-3'(SEQ ID NO:2148)
5'-UUUUUUUUUAGACAGCAAAAACUAU-3'(SEQ ID NO:5744)
3'-CUAAAAAAAAAUCUGUCGUUUUUGAUA-5'(SEQ ID NO:743)
KRAS-4601靶:5'-GATTTTTTTTTAGACAGCAAAAACTAT-3'(SEQ ID NO:2149)
5'-AAGAUUUCCAUUUGUCAAAAAGUAA-3'(SEQ ID NO:5745)
3'-ACUUCUAAAGGUAAACAGUUUUUCAUU-5'(SEQ ID NO:744)
KRAS-4629靶:5'-TGAAGATTTCCATTTGTCAAAAAGTAA-3'(SEQ ID NO:2150)
5'-AGAUUUCCAUUUGUCAAAAAGUAAU-3'(SEQ ID NO:5746)
3'-CUUCUAAAGGUAAACAGUUUUUCAUUA-5'(SEQ ID NO:745)
KRAS-4630靶:5'-GAAGATTTCCATTTGTCAAAAAGTAAT-3'(SEQ ID NO:2151)
5'-GAUUUCCAUUUGUCAAAAAGUAAUG-3'(SEQ ID NO:5747)
3'-UUCUAAAGGUAAACAGUUUUUCAUUAC-5'(SEQ ID NO:746)
KRAS-4631靶:5'-AAGATTTCCATTTGTCAAAAAGTAATG-3'(SEQ ID NO:2152)
5'-AUUUCCAUUUGUCAAAAAGUAAUGA-3'(SEQ ID NO:5748)
3'-UCUAAAGGUAAACAGUUUUUCAUUACU-5'(SEQ ID NO:747)
KRAS-4632靶:5'-AGATTTCCATTTGTCAAAAAGTAATGA-3'(SEQ ID NO:2153)
5'-CAUUUGUCAAAAAGUAAUGAUUUCU-3'(SEQ ID NO:5749)
3'-AGGUAAACAGUUUUUCAUUACUAAAGA-5'(SEQ ID NO:748)
KRAS-4637靶:5'-TCCATTTGTCAAAAAGTAATGATTTCT-3'(SEQ ID NO:2154)
5'-AUUUGUCAAAAAGUAAUGAUUUCUU-3'(SEQ ID NO:5750)
3'-GGUAAACAGUUUUUCAUUACUAAAGAA-5'(SEQ ID NO:749)
KRAS-4638靶:5'-CCATTTGTCAAAAAGTAATGATTTCTT-3'(SEQ ID NO:2155)
5'-UUUGUCAAAAAGUAAUGAUUUCUUG-3'(SEQ ID NO:5751)
3'-GUAAACAGUUUUUCAUUACUAAAGAAC-5'(SEQ ID NO:750)
KRAS-4639靶:5'-CATTTGTCAAAAAGTAATGATTTCTTG-3'(SEQ ID NO:2156)
5'-CAAAAAGUAAUGAUUUCUUGAUAAU-3'(SEQ ID NO:5752)
3'-CAGUUUUUCAUUACUAAAGAACUAUUA-5'(SEQ ID NO:751)
KRAS-4644靶:5'-GTCAAAAAGTAATGATTTCTTGATAAT-3'(SEQ ID NO:2157)
5'-AAAAAGUAAUGAUUUCUUGAUAAUU-3'(SEQ ID NO:5753)
3'-AGUUUUUCAUUACUAAAGAACUAUUAA-5'(SEQ ID NO:752)
KRAS-4645靶:5'-TCAAAAAGTAATGATTTCTTGATAATT-3'(SEQ ID NO:2158)
5'-AAAAGUAAUGAUUUCUUGAUAAUUG-3'(SEQ ID NO:5754)
3'-GUUUUUCAUUACUAAAGAACUAUUAAC-5'(SEQ ID NO:753)
KRAS-4646靶:5'-CAAAAAGTAATGATTTCTTGATAATTG-3'(SEQ ID NO:2159)
5'-AAAGUAAUGAUUUCUUGAUAAUUGU-3'(SEQ ID NO:5755)
3'-UUUUUCAUUACUAAAGAACUAUUAACA-5'(SEQ ID NO:754)
KRAS-4647靶:5'-AAAAAGTAATGATTTCTTGATAATTGT-3'(SEQ ID NO:2160)
5'-AGUAAUGAUUUCUUGAUAAUUGUGU-3'(SEQ ID NO:5756)
3'-UUUCAUUACUAAAGAACUAUUAACACA-5'(SEQ ID NO:755)
KRAS-4649靶:5'-AAAGTAATGATTTCTTGATAATTGTGT-3'(SEQ ID NO:2161)
5'-UAAUGAUUUCUUGAUAAUUGUGUAG-3'(SEQ ID NO:5757)
3'-UCAUUACUAAAGAACUAUUAACACAUC-5'(SEQ ID NO:756)
KRAS-4651靶:5'-AGTAATGATTTCTTGATAATTGTGTAG-3'(SEQ ID NO:2162)
5'-AAUGAUUUCUUGAUAAUUGUGUAGU-3'(SEQ ID NO:5758)
3'-CAUUACUAAAGAACUAUUAACACAUCA-5'(SEQ ID NO:757)
KRAS-4652靶:5'-GTAATGATTTCTTGATAATTGTGTAGT-3'(SEQ ID NO:2163)
5'-UGAUUUCUUGAUAAUUGUGUAGUAA-3'(SEQ ID NO:5759)
3'-UUACUAAAGAACUAUUAACACAUCAUU-5'(SEQ ID NO:758)
KRAS-4654靶:5'-AATGATTTCTTGATAATTGTGTAGTAA-3'(SEQ ID NO:2164)
5'-GAUUUCUUGAUAAUUGUGUAGUAAU-3'(SEQ ID NO:5760)
3'-UACUAAAGAACUAUUAACACAUCAUUA-5'(SEQ ID NO:759)
KRAS-4655靶:5'-ATGATTTCTTGATAATTGTGTAGTAAT-3'(SEQ ID NO:2165)
5'-CUUGAUAAUUGUGUAGUAAUGUUUU-3'(SEQ ID NO:5761)
3'-AAGAACUAUUAACACAUCAUUACAAAA-5'(SEQ ID NO:760)
KRAS-4660靶:5'-TTCTTGATAATTGTGTAGTAATGTTTT-3'(SEQ ID NO:2166)
5'-UUGAUAAUUGUGUAGUAAUGUUUUU-3'(SEQ ID NO:5762)
3'-AGAACUAUUAACACAUCAUUACAAAAA-5'(SEQ ID NO:761)
KRAS-4661靶:5'-TCTTGATAATTGTGTAGTAATGTTTTT-3'(SEQ ID NO:2167)
5'-UGAUAAUUGUGUAGUAAUGUUUUUU-3'(SEQ ID NO:5763)
3'-GAACUAUUAACACAUCAUUACAAAAAA-5'(SEQ ID NO:762)
KRAS-4662靶:5'-CTTGATAATTGTGTAGTAATGTTTTTT-3'(SEQ ID NO:2168)
5'-AUAAUUGUGUAGUAAUGUUUUUUAG-3'(SEQ ID NO:5764)
3'-ACUAUUAACACAUCAUUACAAAAAAUC-5'(SEQ ID NO:763)
KRAS-4664靶:5'-TGATAATTGTGTAGTAATGTTTTTTAG-3'(SEQ ID NO:2169)
5'-AUUGUGUAGUAAUGUUUUUUAGAAC-3'(SEQ ID NO:5765)
3'-AUUAACACAUCAUUACAAAAAAUCUUG-5'(SEQ ID NO:764)
KRAS-4667靶:5'-TAATTGTGTAGTAATGTTTTTTAGAAC-3'(SEQ ID NO:2170)
5'-UGUGUAGUAAUGUUUUUUAGAACCC-3'(SEQ ID NO:5766)
3'-UAACACAUCAUUACAAAAAAUCUUGGG-5'(SEQ ID NO:765)
KRAS-4669靶:5'-ATTGTGTAGTAATGTTTTTTAGAACCC-3'(SEQ ID NO:2171)
5'-GUGUAGUAAUGUUUUUUAGAACCCA-3'(SEQ ID NO:5767)
3'-AACACAUCAUUACAAAAAAUCUUGGGU-5'(SEQ ID NO:766)
KRAS-4670靶:5'-TTGTGTAGTAATGTTTTTTAGAACCCA-3'(SEQ ID NO:2172)
5'-UUAAAGCUGAAUUUAUAUUUAGUAA-3'(SEQ ID NO:5768)
3'-GGAAUUUCGACUUAAAUAUAAAUCAUU-5'(SEQ ID NO:767)
KRAS-4704靶:5'-CCTTAAAGCTGAATTTATATTTAGTAA-3'(SEQ ID NO:2173)
5'-AAAGCUGAAUUUAUAUUUAGUAACU-3'(SEQ ID NO:5769)
3'-AAUUUCGACUUAAAUAUAAAUCAUUGA-5'(SEQ ID NO:768)
KRAS-4706靶:5'-TTAAAGCTGAATTTATATTTAGTAACT-3'(SEQ ID NO:2174)
5'-UUUAUAUUUAGUAACUUCUGUGUUA-3'(SEQ ID NO:5770)
3'-UUAAAUAUAAAUCAUUGAAGACACAAU-5'(SEQ ID NO:769)
KRAS-4715靶:5'-AATTTATATTTAGTAACTTCTGTGTTA-3'(SEQ ID NO:2175)
5'-UUAUAUUUAGUAACUUCUGUGUUAA-3'(SEQ ID NO:5771)
3'-UAAAUAUAAAUCAUUGAAGACACAAUU-5'(SEQ ID NO:770)
KRAS-4716靶:5'-ATTTATATTTAGTAACTTCTGTGTTAA-3'(SEQ ID NO:2176)
5'-UAUAUUUAGUAACUUCUGUGUUAAU-3'(SEQ ID NO:5772)
3'-AAAUAUAAAUCAUUGAAGACACAAUUA-5'(SEQ ID NO:771)
KRAS-4717靶:5'-TTTATATTTAGTAACTTCTGTGTTAAT-3'(SEQ ID NO:2177)
5'-UUAGUAACUUCUGUGUUAAUACUGG-3'(SEQ ID NO:5773)
3'-UAAAUCAUUGAAGACACAAUUAUGACC-5'(SEQ ID NO:772)
KRAS-4722靶:5'-ATTTAGTAACTTCTGTGTTAATACTGG-3'(SEQ ID NO:2178)
5'-UGAAUAGCUGUCAUAAAAUGAAACU-3'(SEQ ID NO:5774)
3'-UGACUUAUCGACAGUAUUUUACUUUGA-5'(SEQ ID NO:773)
KRAS-4773靶:5'-ACTGAATAGCTGTCATAAAATGAAACT-3'(SEQ ID NO:2179)
5'-GAAUAGCUGUCAUAAAAUGAAACUU-3'(SEQ ID NO:5775)
3'-GACUUAUCGACAGUAUUUUACUUUGAA-5'(SEQ ID NO:774)
KRAS-4774靶:5'-CTGAATAGCTGTCATAAAATGAAACTT-3'(SEQ ID NO:2180)
5'-AAAUGAAACUUUCUUUCUAAAGAAA-3'(SEQ ID NO:5776)
3'-AUUUUACUUUGAAAGAAAGAUUUCUUU-5'(SEQ ID NO:775)
KRAS-4788靶:5'-TAAAATGAAACTTTCTTTCTAAAGAAA-3'(SEQ ID NO:2181)
5'-AAUGAAACUUUCUUUCUAAAGAAAG-3'(SEQ ID NO:5777)
3'-UUUUACUUUGAAAGAAAGAUUUCUUUC-5'(SEQ ID NO:776)
KRAS-4789靶:5'-AAAATGAAACTTTCTTTCTAAAGAAAG-3'(SEQ ID NO:2182)
5'-AUGAAACUUUCUUUCUAAAGAAAGA-3'(SEQ ID NO:5778)
3'-UUUACUUUGAAAGAAAGAUUUCUUUCU-5'(SEQ ID NO:777)
KRAS-4790靶:5'-AAATGAAACTTTCTTTCTAAAGAAAGA-3'(SEQ ID NO:2183)
5'-GAAACUUUCUUUCUAAAGAAAGAUA-3'(SEQ ID NO:5779)
3'-UACUUUGAAAGAAAGAUUUCUUUCUAU-5'(SEQ ID NO:778)
KRAS-4792靶:5'-ATGAAACTTTCTTTCTAAAGAAAGATA-3'(SEQ ID NO:2184)
5'-CUUUCUUUCUAAAGAAAGAUACUCA-3'(SEQ ID NO:5780)
3'-UUGAAAGAAAGAUUUCUUUCUAUGAGU-5'(SEQ ID NO:779)
KRAS-4796靶:5'-AACTTTCTTTCTAAAGAAAGATACTCA-3'(SEQ ID NO:2185)
5'-CAUGAGUUCUUGAAGAAUAGUCAUA-3'(SEQ ID NO:5781)
3'-GUGUACUCAAGAACUUCUUAUCAGUAU-5'(SEQ ID NO:780)
KRAS-4821靶:5'-CACATGAGTTCTTGAAGAATAGTCATA-3'(SEQ ID NO:2186)
5'-UUGAAGAAUAGUCAUAACUAGAUUA-3'(SEQ ID NO:5782)
3'-AGAACUUCUUAUCAGUAUUGAUCUAAU-5'(SEQ ID NO:781)
KRAS-4830靶:5'-TCTTGAAGAATAGTCATAACTAGATTA-3'(SEQ ID NO:2187)
5'-UGAAGAAUAGUCAUAACUAGAUUAA-3'(SEQ ID NO:5783)
3'-GAACUUCUUAUCAGUAUUGAUCUAAUU-5'(SEQ ID NO:782)
KRAS-4831靶:5'-CTTGAAGAATAGTCATAACTAGATTAA-3'(SEQ ID NO:2188)
5'-GAAGAAUAGUCAUAACUAGAUUAAG-3'(SEQ ID NO:5784)
3'-AACUUCUUAUCAGUAUUGAUCUAAUUC-5'(SEQ ID NO:783)
KRAS-4832靶:5'-TTGAAGAATAGTCATAACTAGATTAAG-3'(SEQ ID NO:2189)
5'-GAAUAGUCAUAACUAGAUUAAGAUC-3'(SEQ ID NO:5785)
3'-UUCUUAUCAGUAUUGAUCUAAUUCUAG-5'(SEQ ID NO:784)
KRAS-4835靶:5'-AAGAATAGTCATAACTAGATTAAGATC-3'(SEQ ID NO:2190)
5'-AAUAGUCAUAACUAGAUUAAGAUCU-3'(SEQ ID NO:5786)
3'-UCUUAUCAGUAUUGAUCUAAUUCUAGA-5'(SEQ ID NO:785)
KRAS-4836靶:5'-AGAATAGTCATAACTAGATTAAGATCT-3'(SEQ ID NO:2191)
5'-AUAGUCAUAACUAGAUUAAGAUCUG-3'(SEQ ID NO:5787)
3'-CUUAUCAGUAUUGAUCUAAUUCUAGAC-5'(SEQ ID NO:786)
KRAS-4837靶:5'-GAATAGTCATAACTAGATTAAGATCTG-3'(SEQ ID NO:2192)
5'-UAGUCAUAACUAGAUUAAGAUCUGU-3'(SEQ ID NO:5788)
3'-UUAUCAGUAUUGAUCUAAUUCUAGACA-5'(SEQ ID NO:787)
KRAS-4838靶:5'-AATAGTCATAACTAGATTAAGATCTGT-3'(SEQ ID NO:2193)
5'-CAUAACUAGAUUAAGAUCUGUGUUU-3'(SEQ ID NO:5789)
3'-CAGUAUUGAUCUAAUUCUAGACACAAA-5'(SEQ ID NO:788)
KRAS-4842靶:5'-GTCATAACTAGATTAAGATCTGTGTTT-3'(SEQ ID NO:2194)
5'-UAGAUUAAGAUCUGUGUUUUAGUUU-3'(SEQ ID NO:5790)
3'-UGAUCUAAUUCUAGACACAAAAUCAAA-5'(SEQ ID NO:789)
KRAS-4848靶:5'-ACTAGATTAAGATCTGTGTTTTAGTTT-3'(SEQ ID NO:2195)
5'-GAUUAAGAUCUGUGUUUUAGUUUAA-3'(SEQ ID NO:5791)
3'-AUCUAAUUCUAGACACAAAAUCAAAUU-5'(SEQ ID NO:790)
KRAS-4850靶:5'-TAGATTAAGATCTGTGTTTTAGTTTAA-3'(SEQ ID NO:2196)
5'-AUUAAGAUCUGUGUUUUAGUUUAAU-3'(SEQ ID NO:5792)
3'-UCUAAUUCUAGACACAAAAUCAAAUUA-5'(SEQ ID NO:791)
KRAS-4851靶:5'-AGATTAAGATCTGTGTTTTAGTTTAAT-3'(SEQ ID NO:2197)
5'-UAAGAUCUGUGUUUUAGUUUAAUAG-3'(SEQ ID NO:5793)
3'-UAAUUCUAGACACAAAAUCAAAUUAUC-5'(SEQ ID NO:792)
KRAS-4853靶:5'-ATTAAGATCTGTGTTTTAGTTTAATAG-3'(SEQ ID NO:2198)
5'-UGUGUUUUAGUUUAAUAGUUUGAAG-3'(SEQ ID NO:5794)
3'-AGACACAAAAUCAAAUUAUCAAACUUC-5'(SEQ ID NO:793)
KRAS-4860靶:5'-TCTGTGTTTTAGTTTAATAGTTTGAAG-3'(SEQ ID NO:2199)
5'-GUGUUUUAGUUUAAUAGUUUGAAGU-3'(SEQ ID NO:5795)
3'-GACACAAAAUCAAAUUAUCAAACUUCA-5'(SEQ ID NO:794)
KRAS-4861靶:5'-CTGTGTTTTAGTTTAATAGTTTGAAGT-3'(SEQ ID NO:2200)
5'-GUUUUAGUUUAAUAGUUUGAAGUGC-3'(SEQ ID NO:5796)
3'-CACAAAAUCAAAUUAUCAAACUUCACG-5'(SEQ ID NO:795)
KRAS-4863靶:5'-GTGTTTTAGTTTAATAGTTTGAAGTGC-3'(SEQ ID NO:2201)
5'-UUUAGUUUAAUAGUUUGAAGUGCCU-3'(SEQ ID NO:5797)
3'-CAAAAUCAAAUUAUCAAACUUCACGGA-5'(SEQ ID NO:796)
KRAS-4865靶:5'-GTTTTAGTTTAATAGTTTGAAGTGCCT-3'(SEQ ID NO:2202)
5'-UUAGUUUAAUAGUUUGAAGUGCCUG-3'(SEQ ID NO:5798)
3'-AAAAUCAAAUUAUCAAACUUCACGGAC-5'(SEQ ID NO:797)
KRAS-4866靶:5'-TTTTAGTTTAATAGTTTGAAGTGCCTG-3'(SEQ ID NO:2203)
5'-UUGGGAUAAUGAUAGGUAAUUUAGA-3'(SEQ ID NO:5799)
3'-CAAACCCUAUUACUAUCCAUUAAAUCU-5'(SEQ ID NO:798)
KRAS-4892靶:5'-GTTTGGGATAATGATAGGTAATTTAGA-3'(SEQ ID NO:2204)
5'-GGGAUAAUGAUAGGUAAUUUAGAUG-3'(SEQ ID NO:5800)
3'-AACCCUAUUACUAUCCAUUAAAUCUAC-5'(SEQ ID NO:799)
KRAS-4894靶:5'-TTGGGATAATGATAGGTAATTTAGATG-3'(SEQ ID NO:2205)
5'-AUAAUGAUAGGUAAUUUAGAUGAAU-3'(SEQ ID NO:5801)
3'-CCUAUUACUAUCCAUUAAAUCUACUUA-5'(SEQ ID NO:800)
KRAS-4897靶:5'-GGATAATGATAGGTAATTTAGATGAAT-3'(SEQ ID NO:2206)
5'-UAAUGAUAGGUAAUUUAGAUGAAUU-3'(SEQ ID NO:5802)
3'-CUAUUACUAUCCAUUAAAUCUACUUAA-5'(SEQ ID NO:801)
KRAS-4898靶:5'-GATAATGATAGGTAATTTAGATGAATT-3'(SEQ ID NO:2207)
5'-UGAUAGGUAAUUUAGAUGAAUUUAG-3'(SEQ ID NO:5803)
3'-UUACUAUCCAUUAAAUCUACUUAAAUC-5'(SEQ ID NO:802)
KRAS-4901靶:5'-AATGATAGGTAATTTAGATGAATTTAG-3'(SEQ ID NO:2208)
5'-GAUAGGUAAUUUAGAUGAAUUUAGG-3'(SEQ ID NO:5804)
3'-UACUAUCCAUUAAAUCUACUUAAAUCC-5'(SEQ ID NO:803)
KRAS-4902靶:5'-ATGATAGGTAATTTAGATGAATTTAGG-3'(SEQ ID NO:2209)
5'-GUAAUUUAGAUGAAUUUAGGGGAAA-3'(SEQ ID NO:5805)
3'-UCCAUUAAAUCUACUUAAAUCCCCUUU-5'(SEQ ID NO:804)
KRAS-4907靶:5'-AGGTAATTTAGATGAATTTAGGGGAAA-3'(SEQ ID NO:2210)
5'-AAUUUAGAUGAAUUUAGGGGAAAAA-3'(SEQ ID NO:5806)
3'-CAUUAAAUCUACUUAAAUCCCCUUUUU-5'(SEQ ID NO:805)
KRAS-4909靶:5'-GTAATTTAGATGAATTTAGGGGAAAAA-3'(SEQ ID NO:2211)
5'-AUGAAUUUAGGGGAAAAAAAAGUUA-3'(SEQ ID NO:5807)
3'-UCUACUUAAAUCCCCUUUUUUUUCAAU-5'(SEQ ID NO:806)
KRAS-4916靶:5'-AGATGAATTTAGGGGAAAAAAAAGTTA-3'(SEQ ID NO:2212)
5'-UGAAUUUAGGGGAAAAAAAAGUUAU-3'(SEQ ID NO:5808)
3'-CUACUUAAAUCCCCUUUUUUUUCAAUA-5'(SEQ ID NO:807)
KRAS-4917靶:5'-GATGAATTTAGGGGAAAAAAAAGTTAT-3'(SEQ ID NO:2213)
5'-GAAAAAAAAGUUAUCUGCAGAUAUG-3'(SEQ ID NO:5809)
3'-CCCUUUUUUUUCAAUAGACGUCUAUAC-5'(SEQ ID NO:808)
KRAS-4928靶:5'-GGGAAAAAAAAGTTATCTGCAGATATG-3'(SEQ ID NO:2214)
5'-AAAAAAAAGUUAUCUGCAGAUAUGU-3'(SEQ ID NO:5810)
3'-CCUUUUUUUUCAAUAGACGUCUAUACA-5'(SEQ ID NO:809)
KRAS-4929靶:5'-GGAAAAAAAAGTTATCTGCAGATATGT-3'(SEQ ID NO:2215)
5'-AAAGUUAUCUGCAGAUAUGUUGAGG-3'(SEQ ID NO:5811)
3'-UUUUUCAAUAGACGUCUAUACAACUCC-5'(SEQ ID NO:810)
KRAS-4934靶:5'-AAAAAGTTATCTGCAGATATGTTGAGG-3'(SEQ ID NO:2216)
5'-CUUGUGUUUUCAUGUUGAAAAUACU-3'(SEQ ID NO:5812)
3'-CAGAACACAAAAGUACAACUUUUAUGA-5'(SEQ ID NO:811)
KRAS-5035靶:5'-GTCTTGTGTTTTCATGTTGAAAATACT-3'(SEQ ID NO:2217)
5'-UUGUGUUUUCAUGUUGAAAAUACUU-3'(SEQ ID NO:5813)
3'-AGAACACAAAAGUACAACUUUUAUGAA-5'(SEQ ID NO:812)
KRAS-5036靶:5'-TCTTGTGTTTTCATGTTGAAAATACTT-3'(SEQ ID NO:2218)
5'-UGUGUUUUCAUGUUGAAAAUACUUU-3'(SEQ ID NO:5814)
3'-GAACACAAAAGUACAACUUUUAUGAAA-5'(SEQ ID NO:813)
KRAS-5037靶:5'-CTTGTGTTTTCATGTTGAAAATACTTT-3'(SEQ ID NO:2219)
5'-UGUUGAAAAUACUUUUGCAUUUUUC-3'(SEQ ID NO:5815)
3'-GUACAACUUUUAUGAAAACGUAAAAAG-5'(SEQ ID NO:814)
KRAS-5047靶:5'-CATGTTGAAAATACTTTTGCATTTTTC-3'(SEQ ID NO:2220)
5'-GUUGAAAAUACUUUUGCAUUUUUCC-3'(SEQ ID NO:5816)
3'-UACAACUUUUAUGAAAACGUAAAAAGG-5'(SEQ ID NO:815)
KRAS-5048靶:5'-ATGTTGAAAATACTTTTGCATTTTTCC-3'(SEQ ID NO:2221)
5'-UUGAAAAUACUUUUGCAUUUUUCCU-3'(SEQ ID NO:5817)
3'-ACAACUUUUAUGAAAACGUAAAAAGGA-5'(SEQ ID NO:816)
KRAS-5049靶:5'-TGTTGAAAATACTTTTGCATTTTTCCT-3'(SEQ ID NO:2222)
5'-UGAAAAUACUUUUGCAUUUUUCCUU-3'(SEQ ID NO:5818)
3'-CAACUUUUAUGAAAACGUAAAAAGGAA-5'(SEQ ID NO:817)
KRAS-5050靶:5'-GTTGAAAATACTTTTGCATTTTTCCTT-3'(SEQ ID NO:2223)
5'-UUUGCAUUUUUCCUUUGAGUGCCAA-3'(SEQ ID NO:5819)
3'-GAAAACGUAAAAAGGAAACUCACGGUU-5'(SEQ ID NO:818)
KRAS-5060靶:5'-CTTTTGCATTTTTCCTTTGAGTGCCAA-3'(SEQ ID NO:2224)
5'-AGUGCCAAUUUCUUACUAGUACUAU-3'(SEQ ID NO:5820)
3'-ACUCACGGUUAAAGAAUGAUCAUGAUA-5'(SEQ ID NO:819)
KRAS-5077靶:5'-TGAGTGCCAATTTCTTACTAGTACTAT-3'(SEQ ID NO:2225)
5'-CAAUUUCUUACUAGUACUAUUUCUU-3'(SEQ ID NO:5821)
3'-CGGUUAAAGAAUGAUCAUGAUAAAGAA-5'(SEQ ID NO:820)
KRAS-5082靶:5'-GCCAATTTCTTACTAGTACTATTTCTT-3'(SEQ ID NO:2226)
5'-AAUUUCUUACUAGUACUAUUUCUUA-3'(SEQ ID NO:5822)
3'-GGUUAAAGAAUGAUCAUGAUAAAGAAU-5'(SEQ ID NO:821)
KRAS-5083靶:5'-CCAATTTCTTACTAGTACTATTTCTTA-3'(SEQ ID NO:2227)
5'-CUAGUACUAUUUCUUAAUGUAACAU-3'(SEQ ID NO:5823)
3'-AUGAUCAUGAUAAAGAAUUACAUUGUA-5'(SEQ ID NO:822)
KRAS-5092靶:5'-TACTAGTACTATTTCTTAATGTAACAT-3'(SEQ ID NO:2228)
5'-UAGUACUAUUUCUUAAUGUAACAUG-3'(SEQ ID NO:5824)
3'-UGAUCAUGAUAAAGAAUUACAUUGUAC-5'(SEQ ID NO:823)
KRAS-5093靶:5'-ACTAGTACTATTTCTTAATGTAACATG-3'(SEQ ID NO:2229)
5'-CUAUUUCUUAAUGUAACAUGUUUAC-3'(SEQ ID NO:5825)
3'-AUGAUAAAGAAUUACAUUGUACAAAUG-5'(SEQ ID NO:824)
KRAS-5098靶:5'-TACTATTTCTTAATGTAACATGTTTAC-3'(SEQ ID NO:2230)
5'-UAUUUCUUAAUGUAACAUGUUUACC-3'(SEQ ID NO:5826)
3'-UGAUAAAGAAUUACAUUGUACAAAUGG-5'(SEQ ID NO:825)
KRAS-5099靶:5'-ACTATTTCTTAATGTAACATGTTTACC-3'(SEQ ID NO:2231)
5'-AUUUCUUAAUGUAACAUGUUUACCU-3'(SEQ ID NO:5827)
3'-GAUAAAGAAUUACAUUGUACAAAUGGA-5'(SEQ ID NO:826)
KRAS-5100靶:5'-CTATTTCTTAATGTAACATGTTTACCT-3'(SEQ ID NO:2232)
5'-AAUGUAACAUGUUUACCUGGAAUGU-3'(SEQ ID NO:5828)
3'-AAUUACAUUGUACAAAUGGACCUUACA-5'(SEQ ID NO:827)
KRAS-5107靶:5'-TTAATGTAACATGTTTACCTGGAATGT-3'(SEQ ID NO:2233)
5'-UGGAAUGUAUUUUAACUAUUUUUGU-3'(SEQ ID NO:5829)
3'-GGACCUUACAUAAAAUUGAUAAAAACA-5'(SEQ ID NO:828)
KRAS-5124靶:5'-CCTGGAATGTATTTTAACTATTTTTGT-3'(SEQ ID NO:2234)
5'-GAAUGUAUUUUAACUAUUUUUGUAU-3'(SEQ ID NO:5830)
3'-ACCUUACAUAAAAUUGAUAAAAACAUA-5'(SEQ ID NO:829)
KRAS-5126靶:5'-TGGAATGTATTTTAACTATTTTTGTAT-3'(SEQ ID NO:2235)
5'-AAUGUAUUUUAACUAUUUUUGUAUA-3'(SEQ ID NO:5831)
3'-CCUUACAUAAAAUUGAUAAAAACAUAU-5'(SEQ ID NO:830)
KRAS-5127靶:5'-GGAATGTATTTTAACTATTTTTGTATA-3'(SEQ ID NO:2236)
5'-AUGUAUUUUAACUAUUUUUGUAUAG-3'(SEQ ID NO:5832)
3'-CUUACAUAAAAUUGAUAAAAACAUAUC-5'(SEQ ID NO:831)
KRAS-5128靶:5'-GAATGTATTTTAACTATTTTTGTATAG-3'(SEQ ID NO:2237)
5'-UGUAUUUUAACUAUUUUUGUAUAGU-3'(SEQ ID NO:5833)
3'-UUACAUAAAAUUGAUAAAAACAUAUCA-5'(SEQ ID NO:832)
KRAS-5129靶:5'-AATGTATTTTAACTATTTTTGTATAGT-3'(SEQ ID NO:2238)
5'-UAUUUUAACUAUUUUUGUAUAGUGU-3'(SEQ ID NO:5834)
3'-ACAUAAAAUUGAUAAAAACAUAUCACA-5'(SEQ ID NO:833)
KRAS-5131靶:5'-TGTATTTTAACTATTTTTGTATAGTGT-3'(SEQ ID NO:2239)
5'-UUUUAACUAUUUUUGUAUAGUGUAA-3'(SEQ ID NO:5835)
3'-AUAAAAUUGAUAAAAACAUAUCACAUU-5'(SEQ ID NO:834)
KRAS-5133靶:5'-TATTTTAACTATTTTTGTATAGTGTAA-3'(SEQ ID NO:2240)
5'-UUUAACUAUUUUUGUAUAGUGUAAA-3'(SEQ ID NO:5836)
3'-UAAAAUUGAUAAAAACAUAUCACAUUU-5'(SEQ ID NO:835)
KRAS-5134靶:5'-ATTTTAACTATTTTTGTATAGTGTAAA-3'(SEQ ID NO:2241)
5'-UUAACUAUUUUUGUAUAGUGUAAAC-3'(SEQ ID NO:5837)
3'-AAAAUUGAUAAAAACAUAUCACAUUUG-5'(SEQ ID NO:836)
KRAS-5135靶:5'-TTTTAACTATTTTTGTATAGTGTAAAC-3'(SEQ ID NO:2242)
5'-UUUUUGUAUAGUGUAAACUGAAACA-3'(SEQ ID NO:5838)
3'-AUAAAAACAUAUCACAUUUGACUUUGU-5'(SEQ ID NO:837)
KRAS-5142靶:5'-TATTTTTGTATAGTGTAAACTGAAACA-3'(SEQ ID NO:2243)
5'-UUUUGUAUAGUGUAAACUGAAACAU-3'(SEQ ID NO:5839)
3'-UAAAAACAUAUCACAUUUGACUUUGUA-5'(SEQ ID NO:838)
KRAS-5143靶:5'-ATTTTTGTATAGTGTAAACTGAAACAT-3'(SEQ ID NO:2244)
5'-UUUGUAUAGUGUAAACUGAAACAUG-3'(SEQ ID NO:5840)
3'-AAAAACAUAUCACAUUUGACUUUGUAC-5'(SEQ ID NO:839)
KRAS-5144靶:5'-TTTTTGTATAGTGTAAACTGAAACATG-3'(SEQ ID NO:2245)
5'-CUGAAACAUGCACAUUUUGUACAUU-3'(SEQ ID NO:5841)
3'-UUGACUUUGUACGUGUAAAACAUGUAA-5'(SEQ ID NO:840)
KRAS-5159靶:5'-AACTGAAACATGCACATTTTGTACATT-3'(SEQ ID NO:2246)
5'-CAUGCACAUUUUGUACAUUGUGCUU-3'(SEQ ID NO:5842)
3'-UUGUACGUGUAAAACAUGUAACACGAA-5'(SEQ ID NO:841)
KRAS-5165靶:5'-AACATGCACATTTTGTACATTGTGCTT-3'(SEQ ID NO:2247)
5'-CAGUUGUUUUCCAUCAUUUGGUUGC-3'(SEQ ID NO:5843)
3'-AGGUCAACAAAAGGUAGUAAACCAACG-5'(SEQ ID NO:842)
KRAS-5218靶:5'-TCCAGTTGTTTTCCATCATTTGGTTGC-3'(SEQ ID NO:2248)
5'-GUUGUUUUCCAUCAUUUGGUUGCGC-3'(SEQ ID NO:5844)
3'-GUCAACAAAAGGUAGUAAACCAACGCG-5'(SEQ ID NO:843)
KRAS-5220靶:5'-CAGTTGTTTTCCATCATTTGGTTGCGC-3'(SEQ ID NO:2249)
5'-GUUGGUCAUAUCAAACAUUAAAAAU-3'(SEQ ID NO:5845)
3'-UACAACCAGUAUAGUUUGUAAUUUUUA-5'(SEQ ID NO:844)
KRAS-5257靶:5'-ATGTTGGTCATATCAAACATTAAAAAT-3'(SEQ ID NO:2250)
5'-UUGGUCAUAUCAAACAUUAAAAAUG-3'(SEQ ID NO:5846)
3'-ACAACCAGUAUAGUUUGUAAUUUUUAC-5'(SEQ ID NO:845)
KRAS-5258靶:5'-TGTTGGTCATATCAAACATTAAAAATG-3'(SEQ ID NO:2251)
5'-UGGUCAUAUCAAACAUUAAAAAUGA-3'(SEQ ID NO:5847)
3'-CAACCAGUAUAGUUUGUAAUUUUUACU-5'(SEQ ID NO:846)
KRAS-5259靶:5'-GTTGGTCATATCAAACATTAAAAATGA-3'(SEQ ID NO:2252)
5'-CAUAUCAAACAUUAAAAAUGACCAC-3'(SEQ ID NO:5848)
3'-CAGUAUAGUUUGUAAUUUUUACUGGUG-5'(SEQ ID NO:847)
KRAS-5263靶:5'-GTCATATCAAACATTAAAAATGACCAC-3'(SEQ ID NO:2253)
5'-AAUGACCACUCUUUUAAUUGAAAUU-3'(SEQ ID NO:5849)
3'-UUUUACUGGUGAGAAAAUUAACUUUAA-5'(SEQ ID NO:848)
KRAS-5279靶:5'-AAAATGACCACTCTTTTAATTGAAATT-3'(SEQ ID NO:2254)
5'-AUGACCACUCUUUUAAUUGAAAUUA-3'(SEQ ID NO:5850)
3'-UUUACUGGUGAGAAAAUUAACUUUAAU-5'(SEQ ID NO:849)
KRAS-5280靶:5'-AAATGACCACTCTTTTAATTGAAATTA-3'(SEQ ID NO:2255)
5'-CUUUUAAUUGAAAUUAACUUUUAAA-3'(SEQ ID NO:5851)
3'-GAGAAAAUUAACUUUAAUUGAAAAUUU-5'(SEQ ID NO:850)
KRAS-5289靶:5'-CTCTTTTAATTGAAATTAACTTTTAAA-3'(SEQ ID NO:2256)
5'-UUUUAAUUGAAAUUAACUUUUAAAU-3'(SEQ ID NO:5852)
3'-AGAAAAUUAACUUUAAUUGAAAAUUUA-5'(SEQ ID NO:851)
KRAS-5290靶:5'-TCTTTTAATTGAAATTAACTTTTAAAT-3'(SEQ ID NO:2257)
5'-UUAAUUGAAAUUAACUUUUAAAUGU-3'(SEQ ID NO:5853)
3'-AAAAUUAACUUUAAUUGAAAAUUUACA-5'(SEQ ID NO:852)
KRAS-5292靶:5'-TTTTAATTGAAATTAACTTTTAAATGT-3'(SEQ ID NO:2258)
5'-AAUUGAAAUUAACUUUUAAAUGUUU-3'(SEQ ID NO:5854)
3'-AAUUAACUUUAAUUGAAAAUUUACAAA-5'(SEQ ID NO:853)
KRAS-5294靶:5'-TTAATTGAAATTAACTTTTAAATGTTT-3'(SEQ ID NO:2259)
5'-AUUGAAAUUAACUUUUAAAUGUUUA-3'(SEQ ID NO:5855)
3'-AUUAACUUUAAUUGAAAAUUUACAAAU-5'(SEQ ID NO:854)
KRAS-5295靶:5'-TAATTGAAATTAACTTTTAAATGTTTA-3'(SEQ ID NO:2260)
5'-UUGAAAUUAACUUUUAAAUGUUUAU-3'(SEQ ID NO:5856)
3'-UUAACUUUAAUUGAAAAUUUACAAAUA-5'(SEQ ID NO:855)
KRAS-5296靶:5'-AATTGAAATTAACTTTTAAATGTTTAT-3'(SEQ ID NO:2261)
5'-UGAAAUUAACUUUUAAAUGUUUAUA-3'(SEQ ID NO:5857)
3'-UAACUUUAAUUGAAAAUUUACAAAUAU-5'(SEQ ID NO:856)
KRAS-5297靶:5'-ATTGAAATTAACTTTTAAATGTTTATA-3'(SEQ ID NO:2262)
5'-GAAAUUAACUUUUAAAUGUUUAUAG-3'(SEQ ID NO:5858)
3'-AACUUUAAUUGAAAAUUUACAAAUAUC-5'(SEQ ID NO:857)
KRAS-5298靶:5'-TTGAAATTAACTTTTAAATGTTTATAG-3'(SEQ ID NO:2263)
5'-AAAUUAACUUUUAAAUGUUUAUAGG-3'(SEQ ID NO:5859)
3'-ACUUUAAUUGAAAAUUUACAAAUAUCC-5'(SEQ ID NO:858)
KRAS-5299靶:5'-TGAAATTAACTTTTAAATGTTTATAGG-3'(SEQ ID NO:2264)
5'-UUAACUUUUAAAUGUUUAUAGGAGU-3'(SEQ ID NO:5860)
3'-UUAAUUGAAAAUUUACAAAUAUCCUCA-5'(SEQ ID NO:859)
KRAS-5302靶:5'-AATTAACTTTTAAATGTTTATAGGAGT-3'(SEQ ID NO:2265)
5'-CUUUUAAAUGUUUAUAGGAGUAUGU-3'(SEQ ID NO:5861)
3'-UUGAAAAUUUACAAAUAUCCUCAUACA-5'(SEQ ID NO:860)
KRAS-5306靶:5'-AACTTTTAAATGTTTATAGGAGTATGT-3'(SEQ ID NO:2266)
5'-UAAAUGUUUAUAGGAGUAUGUGCUG-3'(SEQ ID NO:5862)
3'-AAAUUUACAAAUAUCCUCAUACACGAC-5'(SEQ ID NO:861)
KRAS-5310靶:5'-TTTAAATGTTTATAGGAGTATGTGCTG-3'(SEQ ID NO:2267)
5'-AAAUGUUUAUAGGAGUAUGUGCUGU-3'(SEQ ID NO:5863)
3'-AAUUUACAAAUAUCCUCAUACACGACA-5'(SEQ ID NO:862)
KRAS-5311靶:5'-TTAAATGTTTATAGGAGTATGTGCTGT-3'(SEQ ID NO:2268)
5'-UGUGAAGUGAUCUAAAAUUUGUAAU-3'(SEQ ID NO:5864)
3'-CGACACUUCACUAGAUUUUAAACAUUA-5'(SEQ ID NO:863)
KRAS-5333靶:5'-GCTGTGAAGTGATCTAAAATTTGTAAT-3'(SEQ ID NO:2269)
5'-UGAAGUGAUCUAAAAUUUGUAAUAU-3'(SEQ ID NO:5865)
3'-ACACUUCACUAGAUUUUAAACAUUAUA-5'(SEQ ID NO:864)
KRAS-5335靶:5'-TGTGAAGTGATCTAAAATTTGTAATAT-3'(SEQ ID NO:2270)
5'-GAAGUGAUCUAAAAUUUGUAAUAUU-3'(SEQ ID NO:5866)
3'-CACUUCACUAGAUUUUAAACAUUAUAA-5'(SEQ ID NO:865)
KRAS-5336靶:5'-GTGAAGTGATCTAAAATTTGTAATATT-3'(SEQ ID NO:2271)
5'-AAGUGAUCUAAAAUUUGUAAUAUUU-3'(SEQ ID NO:5867)
3'-ACUUCACUAGAUUUUAAACAUUAUAAA-5'(SEQ ID NO:866)
KRAS-5337靶:5'-TGAAGTGATCTAAAATTTGTAATATTT-3'(SEQ ID NO:2272)
5'-AGUGAUCUAAAAUUUGUAAUAUUUU-3'(SEQ ID NO:5868)
3'-CUUCACUAGAUUUUAAACAUUAUAAAA-5'(SEQ ID NO:867)
KRAS-5338靶:5'-GAAGTGATCTAAAATTTGTAATATTTT-3'(SEQ ID NO:2273)
5'-GUGAUCUAAAAUUUGUAAUAUUUUU-3'(SEQ ID NO:5869)
3'-UUCACUAGAUUUUAAACAUUAUAAAAA-5'(SEQ ID NO:868)
KRAS-5339靶:5'-AAGTGATCTAAAATTTGTAATATTTTT-3'(SEQ ID NO:2274)
5'-UGAUCUAAAAUUUGUAAUAUUUUUG-3'(SEQ ID NO:5870)
3'-UCACUAGAUUUUAAACAUUAUAAAAAC-5'(SEQ ID NO:869)
KRAS-5340靶:5'-AGTGATCTAAAATTTGTAATATTTTTG-3'(SEQ ID NO:2275)
5'-CUAAAAUUUGUAAUAUUUUUGUCAU-3'(SEQ ID NO:5871)
3'-UAGAUUUUAAACAUUAUAAAAACAGUA-5'(SEQ ID NO:870)
KRAS-5344靶:5'-ATCTAAAATTTGTAATATTTTTGTCAT-3'(SEQ ID NO:2276)
5'-UAAAAUUUGUAAUAUUUUUGUCAUG-3'(SEQ ID NO:5872)
3'-AGAUUUUAAACAUUAUAAAAACAGUAC-5'(SEQ ID NO:871)
KRAS-5345靶:5'-TCTAAAATTTGTAATATTTTTGTCATG-3'(SEQ ID NO:2277)
5'-AUUUGUAAUAUUUUUGUCAUGAACU-3'(SEQ ID NO:5873)
3'-UUUAAACAUUAUAAAAACAGUACUUGA-5'(SEQ ID NO:872)
KRAS-5349靶:5'-AAATTTGTAATATTTTTGTCATGAACT-3'(SEQ ID NO:2278)
5'-UUUGUAAUAUUUUUGUCAUGAACUG-3'(SEQ ID NO:5874)
3'-UUAAACAUUAUAAAAACAGUACUUGAC-5'(SEQ ID NO:873)
KRAS-5350靶:5'-AATTTGTAATATTTTTGTCATGAACTG-3'(SEQ ID NO:2279)
5'-UUGUAAUAUUUUUGUCAUGAACUGU-3'(SEQ ID NO:5875)
3'-UAAACAUUAUAAAAACAGUACUUGACA-5'(SEQ ID NO:874)
KRAS-5351靶:5'-ATTTGTAATATTTTTGTCATGAACTGT-3'(SEQ ID NO:2280)
5'-AAUAUUUUUGUCAUGAACUGUACUA-3'(SEQ ID NO:5876)
3'-CAUUAUAAAAACAGUACUUGACAUGAU-5'(SEQ ID NO:875)
KRAS-5355靶:5'-GTAATATTTTTGTCATGAACTGTACTA-3'(SEQ ID NO:2281)
5'-AUAUUUUUGUCAUGAACUGUACUAC-3'(SEQ ID NO:5877)
3'-AUUAUAAAAACAGUACUUGACAUGAUG-5'(SEQ ID NO:876)
KRAS-5356靶:5'-TAATATTTTTGTCATGAACTGTACTAC-3'(SEQ ID NO:2282)
5'-CUGUACUACUCCUAAUUAUUGUAAU-3'(SEQ ID NO:5878)
3'-UUGACAUGAUGAGGAUUAAUAACAUUA-5'(SEQ ID NO:877)
KRAS-5372靶:5'-AACTGTACTACTCCTAATTATTGTAAT-3'(SEQ ID NO:2283)
5'-UGUACUACUCCUAAUUAUUGUAAUG-3'(SEQ ID NO:5879)
3'-UGACAUGAUGAGGAUUAAUAACAUUAC-5'(SEQ ID NO:878)
KRAS-5373靶:5'-ACTGTACTACTCCTAATTATTGTAATG-3'(SEQ ID NO:2284)
5'-CUAAUUAUUGUAAUGUAAUAAAAAU-3'(SEQ ID NO:5880)
3'-AGGAUUAAUAACAUUACAUUAUUUUUA-5'(SEQ ID NO:879)
KRAS-5383靶:5'-TCCTAATTATTGTAATGTAATAAAAAT-3'(SEQ ID NO:2285)
5'-UAAUUAUUGUAAUGUAAUAAAAAUA-3'(SEQ ID NO:5881)
3'-GGAUUAAUAACAUUACAUUAUUUUUAU-5'(SEQ ID NO:880)
KRAS-5384靶:5'-CCTAATTATTGTAATGTAATAAAAATA-3'(SEQ ID NO:2286)
5'-AUUAUUGUAAUGUAAUAAAAAUAGU-3'(SEQ ID NO:5882)
3'-AUUAAUAACAUUACAUUAUUUUUAUCA-5'(SEQ ID NO:881)
KRAS-5386靶:5'-TAATTATTGTAATGTAATAAAAATAGT-3'(SEQ ID NO:2287)
5'-UAUUGUAAUGUAAUAAAAAUAGUUA-3'(SEQ ID NO:5883)
3'-UAAUAACAUUACAUUAUUUUUAUCAAU-5'(SEQ ID NO:882)
KRAS-5388靶:5'-ATTATTGTAATGTAATAAAAATAGTTA-3'(SEQ ID NO:2288)
5'-AUUGUAAUGUAAUAAAAAUAGUUAC-3'(SEQ ID NO:5884)
3'-AAUAACAUUACAUUAUUUUUAUCAAUG-5'(SEQ ID NO:883)
KRAS-5389靶:5'-TTATTGTAATGTAATAAAAATAGTTAC-3'(SEQ ID NO:2289)
5'-UGUAAUGUAAUAAAAAUAGUUACAG-3'(SEQ ID NO:5885)
3'-UAACAUUACAUUAUUUUUAUCAAUGUC-5'(SEQ ID NO:884)
KRAS-5391靶:5'-ATTGTAATGTAATAAAAATAGTTACAG-3'(SEQ ID NO:2290)
5'-GUAAUGUAAUAAAAAUAGUUACAGU-3'(SEQ ID NO:5886)
3'-AACAUUACAUUAUUUUUAUCAAUGUCA-5'(SEQ ID NO:885)
KRAS-5392靶:5'-TTGTAATGTAATAAAAATAGTTACAGT-3'(SEQ ID NO:2291)
5'-UGUAAUAAAAAUAGUUACAGUGACA-3'(SEQ ID NO:5887)
3'-UUACAUUAUUUUUAUCAAUGUCACUGU-5'(SEQ ID NO:886)
KRAS-5396靶:5'-AATGTAATAAAAATAGTTACAGTGACA-3'(SEQ ID NO:2292)
5'-GUAAUAAAAAUAGUUACAGUGACAA-3'(SEQ ID NO:5888)
3'-UACAUUAUUUUUAUCAAUGUCACUGUU-5'(SEQ ID NO:887)
KRAS-5397靶:5'-ATGTAATAAAAATAGTTACAGTGACAA-3'(SEQ ID NO:2293)
5'-UAAUAAAAAUAGUUACAGUGACAAA-3'(SEQ ID NO:5889)
3'-ACAUUAUUUUUAUCAAUGUCACUGUUU-5'(SEQ ID NO:888)
KRAS-5398靶:5'-TGTAATAAAAATAGTTACAGTGACAAA-3'(SEQ ID NO:2294)
5'-AUAGUUACAGUGACAAAAAAAAAAA-3'(SEQ ID NO:5890)
3'-UUUAUCAAUGUCACUGUUUUUUUUUUU-5'(SEQ ID NO:889)
KRAS-5406靶:5'-AAATAGTTACAGTGACAAAAAAAAAAA-3'(SEQ ID NO:2295)
5'-UAGUUACAGUGACAAAAAAAAAAAA-3'(SEQ ID NO:5891)
3'-UUAUCAAUGUCACUGUUUUUUUUUUUU-5'(SEQ ID NO:890)
KRAS-5407靶:5'-AATAGTTACAGTGACAAAAAAAAAAAA-3'(SEQ ID NO:2296)
5'-GUUACAGUGACAAAAAAAAAAAAAA-3'(SEQ ID NO:5892)
3'-AUCAAUGUCACUGUUUUUUUUUUUUUU-5'(SEQ ID NO:891)
KRAS-5409靶:5'-TAGTTACAGTGACAAAAAAAAAAAAAA-3'(SEQ ID NO:2297)
5'-UGCUGAAAAUGACUGAAUAUAAACU-3'(SEQ ID NO:5893)
3'-GGACGACUUUUACUGACUUAUAUUUGA-5'(SEQ ID NO:2298)
KRAS-172靶:5'-CCTGCTGAAAATGACTGAATATAAACT-3'(SEQ ID NO:3704)
5'-AAAUGACUGAAUAUAAACUUGUGGU-3'(SEQ ID NO:5894)
3'-CUUUUACUGACUUAUAUUUGAACACCA-5'(SEQ ID NO:2299)
KRAS-178靶:5'-GAAAATGACTGAATATAAACTTGTGGT-3'(SEQ ID NO:3705)
5'-GACUGAAUAUAAACUUGUGGUAGUU-3'(SEQ ID NO:5895)
3'-UACUGACUUAUAUUUGAACACCAUCAA-5'(SEQ ID NO:2300)
KRAS-182靶:5'-ATGACTGAATATAAACTTGTGGTAGTT-3'(SEQ ID NO:3706)
5'-AGCUAAUUCAGAAUCAUUUUGUGGA-3'(SEQ ID NO:5896)
3'-UGUCGAUUAAGUCUUAGUAAAACACCU-5'(SEQ ID NO:2301)
KRAS-244靶:5'-ACAGCTAATTCAGAATCATTTTGTGGA-3'(SEQ ID NO:3707)
5'-ACGAAUAUGAUCCAACAAUAGAGGA-3'(SEQ ID NO:5897)
3'-CCUGCUUAUACUAGGUUGUUAUCUCCU-5'(SEQ ID NO:2302)
KRAS-268靶:5'-GGACGAATATGATCCAACAATAGAGGA-3'(SEQ ID NO:3708)
5'-AGCAAGUAGUAAUUGAUGGAGAAAC-3'(SEQ ID NO:5898)
3'-CUUCGUUCAUCAUUAACUACCUCUUUG-5'(SEQ ID NO:2303)
KRAS-304靶:5'-GAAGCAAGTAGTAATTGATGGAGAAAC-3'(SEQ ID NO:3709)
5'-GGAGGGCUUUCUUUGUGUAUUUGCC-3'(SEQ ID NO:5899)
3'-CCCCUCCCGAAAGAAACACAUAAACGG-5'(SEQ ID NO:2304)
KRAS-404靶:5'-GGGGAGGGCTTTCTTTGTGTATTTGCC-3'(SEQ ID NO:3710)
5'-UCUUUGUGUAUUUGCCAUAAAUAAU-3'(SEQ ID NO:5900)
3'-AAAGAAACACAUAAACGGUAUUUAUUA-5'(SEQ ID NO:2305)
KRAS-413靶:5'-TTTCTTTGTGTATTTGCCATAAATAAT-3'(SEQ ID NO:3711)
5'-CUUUGUGUAUUUGCCAUAAAUAAUA-3'(SEQ ID NO:5901)
3'-AAGAAACACAUAAACGGUAUUUAUUAU-5'(SEQ ID NO:2306)
KRAS-414靶:5'-TTCTTTGTGTATTTGCCATAAATAATA-3'(SEQ ID NO:3712)
5'-UUUGUGUAUUUGCCAUAAAUAAUAC-3'(SEQ ID NO:5902)
3'-AGAAACACAUAAACGGUAUUUAUUAUG-5'(SEQ ID NO:2307)
KRAS-415靶:5'-TCTTTGTGTATTTGCCATAAATAATAC-3'(SEQ ID NO:3713)
5'-UUGUGUAUUUGCCAUAAAUAAUACU-3'(SEQ ID NO:5903)
3'-GAAACACAUAAACGGUAUUUAUUAUGA-5'(SEQ ID NO:2308)
KRAS-416靶:5'-CTTTGTGTATTTGCCATAAATAATACT-3'(SEQ ID NO:3714)
5'-GUAUUUGCCAUAAAUAAUACUAAAU-3'(SEQ ID NO:5904)
3'-CACAUAAACGGUAUUUAUUAUGAUUUA-5'(SEQ ID NO:2309)
KRAS-420靶:5'-GTGTATTTGCCATAAATAATACTAAAT-3'(SEQ ID NO:3715)
5'-UAUUUGCCAUAAAUAAUACUAAAUC-3'(SEQ ID NO:5905)
3'-ACAUAAACGGUAUUUAUUAUGAUUUAG-5'(SEQ ID NO:2310)
KRAS-421靶:5'-TGTATTTGCCATAAATAATACTAAATC-3'(SEQ ID NO:3716)
5'-CCAUAAAUAAUACUAAAUCAUUUGA-3'(SEQ ID NO:5906)
3'-ACGGUAUUUAUUAUGAUUUAGUAAACU-5'(SEQ ID NO:2311)
KRAS-427靶:5'-TGCCATAAATAATACTAAATCATTTGA-3'(SEQ ID NO:3717)
5'-CAUAAAUAAUACUAAAUCAUUUGAA-3'(SEQ ID NO:5907)
3'-CGGUAUUUAUUAUGAUUUAGUAAACUU-5'(SEQ ID NO:2312)
KRAS-428靶:5'-GCCATAAATAATACTAAATCATTTGAA-3'(SEQ ID NO:3718)
5'-UAAAUAAUACUAAAUCAUUUGAAGA-3'(SEQ ID NO:5908)
3'-GUAUUUAUUAUGAUUUAGUAAACUUCU-5'(SEQ ID NO:2313)
KRAS-430靶:5'-CATAAATAATACTAAATCATTTGAAGA-3'(SEQ ID NO:3719)
5'-AAAUAAUACUAAAUCAUUUGAAGAU-3'(SEQ ID NO:5909)
3'-UAUUUAUUAUGAUUUAGUAAACUUCUA-5'(SEQ ID NO:2314)
KRAS-431靶:5'-ATAAATAATACTAAATCATTTGAAGAT-3'(SEQ ID NO:3720)
5'-AAUAAUACUAAAUCAUUUGAAGAUA-3'(SEQ ID NO:5910)
3'-AUUUAUUAUGAUUUAGUAAACUUCUAU-5'(SEQ ID NO:2315)
KRAS-432靶:5'-TAAATAATACTAAATCATTTGAAGATA-3'(SEQ ID NO:3721)
5'-AUAAUACUAAAUCAUUUGAAGAUAU-3'(SEQ ID NO:5911)
3'-UUUAUUAUGAUUUAGUAAACUUCUAUA-5'(SEQ ID NO:2316)
KRAS-433靶:5'-AAATAATACTAAATCATTTGAAGATAT-3'(SEQ ID NO:3722)
5'-AUUUGAAGAUAUUCACCAUUAUAGA-3'(SEQ ID NO:5912)
3'-AGUAAACUUCUAUAAGUGGUAAUAUCU-5'(SEQ ID NO:2317)
KRAS-446靶:5'-TCATTTGAAGATATTCACCATTATAGA-3'(SEQ ID NO:3723)
5'-UUGAAGAUAUUCACCAUUAUAGAGA-3'(SEQ ID NO:5913)
3'-UAAACUUCUAUAAGUGGUAAUAUCUCU-5'(SEQ ID NO:2318)
KRAS-448靶:5'-ATTTGAAGATATTCACCATTATAGAGA-3'(SEQ ID NO:3724)
5'-UGAAGAUAUUCACCAUUAUAGAGAA-3'(SEQ ID NO:5914)
3'-AAACUUCUAUAAGUGGUAAUAUCUCUU-5'(SEQ ID NO:2319)
KRAS-449靶:5'-TTTGAAGATATTCACCATTATAGAGAA-3'(SEQ ID NO:3725)
5'-GAAGAUAUUCACCAUUAUAGAGAAC-3'(SEQ ID NO:5915)
3'-AACUUCUAUAAGUGGUAAUAUCUCUUG-5'(SEQ ID NO:2320)
KRAS-450靶:5'-TTGAAGATATTCACCATTATAGAGAAC-3'(SEQ ID NO:3726)
5'-AAGAUAUUCACCAUUAUAGAGAACA-3'(SEQ ID NO:5916)
3'-ACUUCUAUAAGUGGUAAUAUCUCUUGU-5'(SEQ ID NO:2321)
KRAS-451靶:5'-TGAAGATATTCACCATTATAGAGAACA-3'(SEQ ID NO:3727)
5'-CCAUUAUAGAGAACAAAUUAAAAGA-3'(SEQ ID NO:5917)
3'-GUGGUAAUAUCUCUUGUUUAAUUUUCU-5'(SEQ ID NO:2322)
KRAS-461靶:5'-CACCATTATAGAGAACAAATTAAAAGA-3'(SEQ ID NO:3728)
5'-AUUAUAGAGAACAAAUUAAAAGAGU-3'(SEQ ID NO:5918)
3'-GGUAAUAUCUCUUGUUUAAUUUUCUCA-5'(SEQ ID NO:2323)
KRAS-463靶:5'-CCATTATAGAGAACAAATTAAAAGAGT-3'(SEQ ID NO:3729)
5'-UUAUAGAGAACAAAUUAAAAGAGUU-3'(SEQ ID NO:5919)
3'-GUAAUAUCUCUUGUUUAAUUUUCUCAA-5'(SEQ ID NO:2324)
KRAS-464靶:5'-CATTATAGAGAACAAATTAAAAGAGTT-3'(SEQ ID NO:3730)
5'-UAUAGAGAACAAAUUAAAAGAGUUA-3'(SEQ ID NO:5920)
3'-UAAUAUCUCUUGUUUAAUUUUCUCAAU-5'(SEQ ID NO:2325)
KRAS-465靶:5'-ATTATAGAGAACAAATTAAAAGAGTTA-3'(SEQ ID NO:3731)
5'-AUAGAGAACAAAUUAAAAGAGUUAA-3'(SEQ ID NO:5921)
3'-AAUAUCUCUUGUUUAAUUUUCUCAAUU-5'(SEQ ID NO:2326)
KRAS-466靶:5'-TTATAGAGAACAAATTAAAAGAGTTAA-3'(SEQ ID NO:3732)
5'-CUAGUAGGAAAUAAAUGUGAUUUGC-3'(SEQ ID NO:5922)
3'-AGGAUCAUCCUUUAUUUACACUAAACG-5'(SEQ ID NO:2327)
KRAS-516靶:5'-TCCTAGTAGGAAATAAATGTGATTTGC-3'(SEQ ID NO:3733)
5'-UAGUAGGAAAUAAAUGUGAUUUGCC-3'(SEQ ID NO:5923)
3'-GGAUCAUCCUUUAUUUACACUAAACGG-5'(SEQ ID NO:2328)
KRAS-517靶:5'-CCTAGTAGGAAATAAATGTGATTTGCC-3'(SEQ ID NO:3734)
5'-AAGAAGUUAUGGAAUUCCUUUUAUU-3'(SEQ ID NO:5924)
3'-CGUUCUUCAAUACCUUAAGGAAAAUAA-5'(SEQ ID NO:2329)
KRAS-581靶:5'-GCAAGAAGTTATGGAATTCCTTTTATT-3'(SEQ ID NO:3735)
5'-AAGUUAUGGAAUUCCUUUUAUUGAA-3'(SEQ ID NO:5925)
3'-UCUUCAAUACCUUAAGGAAAAUAACUU-5'(SEQ ID NO:2330)
KRAS-584靶:5'-AGAAGTTATGGAATTCCTTTTATTGAA-3'(SEQ ID NO:3736)
5'-AGUUAUGGAAUUCCUUUUAUUGAAA-3'(SEQ ID NO:5926)
3'-CUUCAAUACCUUAAGGAAAAUAACUUU-5'(SEQ ID NO:2331)
KRAS-585靶:5'-GAAGTTATGGAATTCCTTTTATTGAAA-3'(SEQ ID NO:3737)
5'-GUUAUGGAAUUCCUUUUAUUGAAAC-3'(SEQ ID NO:5927)
3'-UUCAAUACCUUAAGGAAAAUAACUUUG-5'(SEQ ID NO:2332)
KRAS-586靶:5'-AAGTTATGGAATTCCTTTTATTGAAAC-3'(SEQ ID NO:3738)
5'-UUAUGGAAUUCCUUUUAUUGAAACA-3'(SEQ ID NO:5928)
3'-UCAAUACCUUAAGGAAAAUAACUUUGU-5'(SEQ ID NO:2333)
KRAS-587靶:5'-AGTTATGGAATTCCTTTTATTGAAACA-3'(SEQ ID NO:3739)
5'-UGGAGGAUGCUUUUUAUACAUUGGU-3'(SEQ ID NO:5929)
3'-UCACCUCCUACGAAAAAUAUGUAACCA-5'(SEQ ID NO:2334)
KRAS-634靶:5'-AGTGGAGGATGCTTTTTATACATTGGT-3'(SEQ ID NO:3740)
5'-GAGGAUGCUUUUUAUACAUUGGUGA-3'(SEQ ID NO:5930)
3'-ACCUCCUACGAAAAAUAUGUAACCACU-5'(SEQ ID NO:2335)
KRAS-636靶:5'-TGGAGGATGCTTTTTATACATTGGTGA-3'(SEQ ID NO:3741)
5'-ACAGAUUGAAAAAAAUCAGCAAAGA-3'(SEQ ID NO:5931)
3'-UAUGUCUAACUUUUUUUAGUCGUUUCU-5'(SEQ ID NO:2336)
KRAS-676靶:5'-ATACAGATTGAAAAAAATCAGCAAAGA-3'(SEQ ID NO:3742)
5'-CAGAUUGAAAAAAAUCAGCAAAGAA-3'(SEQ ID NO:5932)
3'-AUGUCUAACUUUUUUUAGUCGUUUCUU-5'(SEQ ID NO:2337)
KRAS-677靶:5'-TACAGATTGAAAAAAATCAGCAAAGAA-3'(SEQ ID NO:3743)
5'-GAUUGAAAAAAAUCAGCAAAGAAGA-3'(SEQ ID NO:5933)
3'-GUCUAACUUUUUUUAGUCGUUUCUUCU-5'(SEQ ID NO:2338)
KRAS-679靶:5'-CAGATTGAAAAAAATCAGCAAAGAAGA-3'(SEQ ID NO:3744)
5'-AUUGAAAAAAAUCAGCAAAGAAGAA-3'(SEQ ID NO:5934)
3'-UCUAACUUUUUUUAGUCGUUUCUUCUU-5'(SEQ ID NO:2339)
KRAS-680靶:5'-AGATTGAAAAAAATCAGCAAAGAAGAA-3'(SEQ ID NO:3745)
5'-UUGAAAAAAAUCAGCAAAGAAGAAA-3'(SEQ ID NO:5935)
3'-CUAACUUUUUUUAGUCGUUUCUUCUUU-5'(SEQ ID NO:2340)
KRAS-681靶:5'-GATTGAAAAAAATCAGCAAAGAAGAAA-3'(SEQ ID NO:3746)
5'-UGAAAAAAAUCAGCAAAGAAGAAAA-3'(SEQ ID NO:5936)
3'-UAACUUUUUUUAGUCGUUUCUUCUUUU-5'(SEQ ID NO:2341)
KRAS-682靶:5'-ATTGAAAAAAATCAGCAAAGAAGAAAA-3'(SEQ ID NO:3747)
5'-UCCUGGCUGUGUGAAAAUUAAAAAA-3'(SEQ ID NO:5937)
3'-UGAGGACCGACACACUUUUAAUUUUUU-5'(SEQ ID NO:2342)
KRAS-710靶:5'-ACTCCTGGCTGTGTGAAAATTAAAAAA-3'(SEQ ID NO:3748)
5'-GGCUGUGUGAAAAUUAAAAAAUGCA-3'(SEQ ID NO:5938)
3'-GACCGACACACUUUUAAUUUUUUACGU-5'(SEQ ID NO:2343)
KRAS-714靶:5'-CTGGCTGTGTGAAAATTAAAAAATGCA-3'(SEQ ID NO:3749)
5'-GUGUGAAAAUUAAAAAAUGCAUUAU-3'(SEQ ID NO:5939)
3'-GACACACUUUUAAUUUUUUACGUAAUA-5'(SEQ ID NO:2344)
KRAS-718靶:5'-CTGTGTGAAAATTAAAAAATGCATTAT-3'(SEQ ID NO:3750)
5'-UGUGAAAAUUAAAAAAUGCAUUAUA-3'(SEQ ID NO:5940)
3'-ACACACUUUUAAUUUUUUACGUAAUAU-5'(SEQ ID NO:2345)
KRAS-719靶:5'-TGTGTGAAAATTAAAAAATGCATTATA-3'(SEQ ID NO:3751)
5'-GUGAAAAUUAAAAAAUGCAUUAUAA-3'(SEQ ID NO:5941)
3'-CACACUUUUAAUUUUUUACGUAAUAUU-5'(SEQ ID NO:2346)
KRAS-720靶:5'-GTGTGAAAATTAAAAAATGCATTATAA-3'(SEQ ID NO:3752)
5'-UGAAAAUUAAAAAAUGCAUUAUAAU-3'(SEQ ID NO:5942)
3'-ACACUUUUAAUUUUUUACGUAAUAUUA-5'(SEQ ID NO:2347)
KRAS-721靶:5'-TGTGAAAATTAAAAAATGCATTATAAT-3'(SEQ ID NO:3753)
5'-AAAAUUAAAAAAUGCAUUAUAAUGU-3'(SEQ ID NO:5943)
3'-ACUUUUAAUUUUUUACGUAAUAUUACA-5'(SEQ ID NO:2348)
KRAS-723靶:5'-TGAAAATTAAAAAATGCATTATAATGT-3'(SEQ ID NO:3754)
5'-AAAUUAAAAAAUGCAUUAUAAUGUA-3'(SEQ ID NO:5944)
3'-CUUUUAAUUUUUUACGUAAUAUUACAU-5'(SEQ ID NO:2349)
KRAS-724靶:5'-GAAAATTAAAAAATGCATTATAATGTA-3'(SEQ ID NO:3755)
5'-AAUUAAAAAAUGCAUUAUAAUGUAA-3'(SEQ ID NO:5945)
3'-UUUUAAUUUUUUACGUAAUAUUACAUU-5'(SEQ ID NO:2350)
KRAS-725靶:5'-AAAATTAAAAAATGCATTATAATGTAA-3'(SEQ ID NO:3756)
5'-AUUAAAAAAUGCAUUAUAAUGUAAU-3'(SEQ ID NO:5946)
3'-UUUAAUUUUUUACGUAAUAUUACAUUA-5'(SEQ ID NO:2351)
KRAS-726靶:5'-AAATTAAAAAATGCATTATAATGTAAT-3'(SEQ ID NO:3757)
5'-UAAAAAAUGCAUUAUAAUGUAAUCU-3'(SEQ ID NO:5947)
3'-UAAUUUUUUACGUAAUAUUACAUUAGA-5'(SEQ ID NO:2352)
KRAS-728靶:5'-ATTAAAAAATGCATTATAATGTAATCT-3'(SEQ ID NO:3758)
5'-UGCAUUAUAAUGUAAUCUGGGUGUU-3'(SEQ ID NO:5948)
3'-UUACGUAAUAUUACAUUAGACCCACAA-5'(SEQ ID NO:2353)
KRAS-735靶:5'-AATGCATTATAATGTAATCTGGGTGTT-3'(SEQ ID NO:3759)
5'-UUCGAGAAAUUCGAAAACAUAAAGA-3'(SEQ ID NO:5949)
3'-UCAAGCUCUUUAAGCUUUUGUAUUUCU-5'(SEQ ID NO:2354)
KRAS-782靶:5'-AGTTCGAGAAATTCGAAAACATAAAGA-3'(SEQ ID NO:3760)
5'-UCGAGAAAUUCGAAAACAUAAAGAA-3'(SEQ ID NO:5950)
3'-CAAGCUCUUUAAGCUUUUGUAUUUCUU-5'(SEQ ID NO:2355)
KRAS-783靶:5'-GTTCGAGAAATTCGAAAACATAAAGAA-3'(SEQ ID NO:3761)
5'-CGAGAAAUUCGAAAACAUAAAGAAA-3'(SEQ ID NO:5951)
3'-AAGCUCUUUAAGCUUUUGUAUUUCUUU-5'(SEQ ID NO:2356)
KRAS-784靶:5'-TTCGAGAAATTCGAAAACATAAAGAAA-3'(SEQ ID NO:3762)
5'-GAAAUUCGAAAACAUAAAGAAAAGA-3'(SEQ ID NO:5952)
3'-CUCUUUAAGCUUUUGUAUUUCUUUUCU-5'(SEQ ID NO:2357)
KRAS-787靶:5'-GAGAAATTCGAAAACATAAAGAAAAGA-3'(SEQ ID NO:3763)
5'-UCGAAAACAUAAAGAAAAGAUGAGC-3'(SEQ ID NO:5953)
3'-UAAGCUUUUGUAUUUCUUUUCUACUCG-5'(SEQ ID NO:2358)
KRAS-792靶:5'-ATTCGAAAACATAAAGAAAAGATGAGC-3'(SEQ ID NO:3764)
5'-CGAAAACAUAAAGAAAAGAUGAGCA-3'(SEQ ID NO:5954)
3'-AAGCUUUUGUAUUUCUUUUCUACUCGU-5'(SEQ ID NO:2359)
KRAS-793靶:5'-TTCGAAAACATAAAGAAAAGATGAGCA-3'(SEQ ID NO:3765)
5'-AAAGAUGGUAAAAAGAAGAAAAAGA-3'(SEQ ID NO:5955)
3'-CGUUUCUACCAUUUUUCUUCUUUUUCU-5'(SEQ ID NO:2360)
KRAS-817靶:5'-GCAAAGATGGTAAAAAGAAGAAAAAGA-3'(SEQ ID NO:3766)
5'-AAGAUGGUAAAAAGAAGAAAAAGAA-3'(SEQ ID NO:5956)
3'-GUUUCUACCAUUUUUCUUCUUUUUCUU-5'(SEQ ID NO:2361)
KRAS-818靶:5'-CAAAGATGGTAAAAAGAAGAAAAAGAA-3'(SEQ ID NO:3767)
5'-GAUGGUAAAAAGAAGAAAAAGAAGU-3'(SEQ ID NO:5957)
3'-UUCUACCAUUUUUCUUCUUUUUCUUCA-5'(SEQ ID NO:2362)
KRAS-820靶:5'-AAGATGGTAAAAAGAAGAAAAAGAAGT-3'(SEQ ID NO:3768)
5'-AUGGUAAAAAGAAGAAAAAGAAGUC-3'(SEQ ID NO:5958)
3'-UCUACCAUUUUUCUUCUUUUUCUUCAG-5'(SEQ ID NO:2363)
KRAS-821靶:5'-AGATGGTAAAAAGAAGAAAAAGAAGTC-3'(SEQ ID NO:3769)
5'-AAAAAGAAGAAAAAGAAGUCAAAGA-3'(SEQ ID NO:5959)
3'-CAUUUUUCUUCUUUUUCUUCAGUUUCU-5'(SEQ ID NO:2364)
KRAS-826靶:5'-GTAAAAAGAAGAAAAAGAAGTCAAAGA-3'(SEQ ID NO:3770)
5'-AAAAGAAGAAAAAGAAGUCAAAGAC-3'(SEQ ID NO:5960)
3'-AUUUUUCUUCUUUUUCUUCAGUUUCUG-5'(SEQ ID NO:2365)
KRAS-827靶:5'-TAAAAAGAAGAAAAAGAAGTCAAAGAC-3'(SEQ ID NO:3771)
5'-AAAGAAGAAAAAGAAGUCAAAGACA-3'(SEQ ID NO:5961)
3'-UUUUUCUUCUUUUUCUUCAGUUUCUGU-5'(SEQ ID NO:2366)
KRAS-828靶:5'-AAAAAGAAGAAAAAGAAGTCAAAGACA-3'(SEQ ID NO:3772)
5'-UCAAAGACAAAGUGUGUAAUUAUGU-3'(SEQ ID NO:5962)
3'-UCAGUUUCUGUUUCACACAUUAAUACA-5'(SEQ ID NO:2367)
KRAS-844靶:5'-AGTCAAAGACAAAGTGTGTAATTATGT-3'(SEQ ID NO:3773)
5'-CAAAGACAAAGUGUGUAAUUAUGUA-3'(SEQ ID NO:5963)
3'-CAGUUUCUGUUUCACACAUUAAUACAU-5'(SEQ ID NO:2368)
KRAS-845靶:5'-GTCAAAGACAAAGTGTGTAATTATGTA-3'(SEQ ID NO:3774)
5'-GACAAAGUGUGUAAUUAUGUAAAUA-3'(SEQ ID NO:5964)
3'-UUCUGUUUCACACAUUAAUACAUUUAU-5'(SEQ ID NO:2369)
KRAS-849靶:5'-AAGACAAAGTGTGTAATTATGTAAATA-3'(SEQ ID NO:3775)
5'-CAAAGUGUGUAAUUAUGUAAAUACA-3'(SEQ ID NO:5965)
3'-CUGUUUCACACAUUAAUACAUUUAUGU-5'(SEQ ID NO:2370)
KRAS-851靶:5'-GACAAAGTGTGTAATTATGTAAATACA-3'(SEQ ID NO:3776)
5'-GUGUGUAAUUAUGUAAAUACAAUUU-3'(SEQ ID NO:5966)
3'-UUCACACAUUAAUACAUUUAUGUUAAA-5'(SEQ ID NO:2371)
KRAS-855靶:5'-AAGTGTGTAATTATGTAAATACAATTT-3'(SEQ ID NO:3777)
5'-GUGUAAUUAUGUAAAUACAAUUUGU-3'(SEQ ID NO:5967)
3'-CACACAUUAAUACAUUUAUGUUAAACA-5'(SEQ ID NO:2372)
KRAS-857靶:5'-GTGTGTAATTATGTAAATACAATTTGT-3'(SEQ ID NO:3778)
5'-GUAAUUAUGUAAAUACAAUUUGUAC-3'(SEQ ID NO:5968)
3'-CACAUUAAUACAUUUAUGUUAAACAUG-5'(SEQ ID NO:2373)
KRAS-859靶:5'-GTGTAATTATGTAAATACAATTTGTAC-3'(SEQ ID NO:3779)
5'-UAAUUAUGUAAAUACAAUUUGUACU-3'(SEQ ID NO:5969)
3'-ACAUUAAUACAUUUAUGUUAAACAUGA-5'(SEQ ID NO:2374)
KRAS-860靶:5'-TGTAATTATGTAAATACAATTTGTACT-3'(SEQ ID NO:3780)
5'-UAUGUAAAUACAAUUUGUACUUUUU-3'(SEQ ID NO:5970)
3'-UAAUACAUUUAUGUUAAACAUGAAAAA-5'(SEQ ID NO:2375)
KRAS-864靶:5'-ATTATGTAAATACAATTTGTACTTTTT-3'(SEQ ID NO:3781)
5'-AUGUAAAUACAAUUUGUACUUUUUU-3'(SEQ ID NO:5971)
3'-AAUACAUUUAUGUUAAACAUGAAAAAA-5'(SEQ ID NO:2376)
KRAS-865靶:5'-TTATGTAAATACAATTTGTACTTTTTT-3'(SEQ ID NO:3782)
5'-UGUAAAUACAAUUUGUACUUUUUUC-3'(SEQ ID NO:5972)
3'-AUACAUUUAUGUUAAACAUGAAAAAAG-5'(SEQ ID NO:2377)
KRAS-866靶:5'-TATGTAAATACAATTTGTACTTTTTTC-3'(SEQ ID NO:3783)
5'-GUAAAUACAAUUUGUACUUUUUUCU-3'(SEQ ID NO:5973)
3'-UACAUUUAUGUUAAACAUGAAAAAAGA-5'(SEQ ID NO:2378)
KRAS-867靶:5'-ATGTAAATACAATTTGTACTTTTTTCT-3'(SEQ ID NO:3784)
5'-ACAAUUUGUACUUUUUUCUUAAGGC-3'(SEQ ID NO:5974)
3'-UAUGUUAAACAUGAAAAAAGAAUUCCG-5'(SEQ ID NO:2379)
KRAS-873靶:5'-ATACAATTTGTACTTTTTTCTTAAGGC-3'(SEQ ID NO:3785)
5'-CAAUUUGUACUUUUUUCUUAAGGCA-3'(SEQ ID NO:5975)
3'-AUGUUAAACAUGAAAAAAGAAUUCCGU-5'(SEQ ID NO:2380)
KRAS-874靶:5'-TACAATTTGTACTTTTTTCTTAAGGCA-3'(SEQ ID NO:3786)
5'-UACUAGUACAAGUGGUAAUUUUUGU-3'(SEQ ID NO:5976)
3'-GUAUGAUCAUGUUCACCAUUAAAAACA-5'(SEQ ID NO:2381)
KRAS-899靶:5'-CATACTAGTACAAGTGGTAATTTTTGT-3'(SEQ ID NO:3787)
5'-ACUAGUACAAGUGGUAAUUUUUGUA-3'(SEQ ID NO:5977)
3'-UAUGAUCAUGUUCACCAUUAAAAACAU-5'(SEQ ID NO:2382)
KRAS-900靶:5'-ATACTAGTACAAGTGGTAATTTTTGTA-3'(SEQ ID NO:3788)
5'-ACAAGUGGUAAUUUUUGUACAUUAC-3'(SEQ ID NO:5978)
3'-CAUGUUCACCAUUAAAAACAUGUAAUG-5'(SEQ ID NO:2383)
KRAS-906靶:5'-GTACAAGTGGTAATTTTTGTACATTAC-3'(SEQ ID NO:3789)
5'-CAAGUGGUAAUUUUUGUACAUUACA-3'(SEQ ID NO:5979)
3'-AUGUUCACCAUUAAAAACAUGUAAUGU-5'(SEQ ID NO:2384)
KRAS-907靶:5'-TACAAGTGGTAATTTTTGTACATTACA-3'(SEQ ID NO:3790)
5'-UAAUUUUUGUACAUUACACUAAAUU-3'(SEQ ID NO:5980)
3'-CCAUUAAAAACAUGUAAUGUGAUUUAA-5'(SEQ ID NO:2385)
KRAS-914靶:5'-GGTAATTTTTGTACATTACACTAAATT-3'(SEQ ID NO:3791)
5'-AAUUUUUGUACAUUACACUAAAUUA-3'(SEQ ID NO:5981)
3'-CAUUAAAAACAUGUAAUGUGAUUUAAU-5'(SEQ ID NO:2386)
KRAS-915靶:5'-GTAATTTTTGTACATTACACTAAATTA-3'(SEQ ID NO:3792)
5'-AUUUUUGUACAUUACACUAAAUUAU-3'(SEQ ID NO:5982)
3'-AUUAAAAACAUGUAAUGUGAUUUAAUA-5'(SEQ ID NO:2387)
KRAS-916靶:5'-TAATTTTTGTACATTACACTAAATTAT-3'(SEQ ID NO:3793)
5'-UUUUUGUACAUUACACUAAAUUAUU-3'(SEQ ID NO:5983)
3'-UUAAAAACAUGUAAUGUGAUUUAAUAA-5'(SEQ ID NO:2388)
KRAS-917靶:5'-AATTTTTGTACATTACACTAAATTATT-3'(SEQ ID NO:3794)
5'-UUUUGUACAUUACACUAAAUUAUUA-3'(SEQ ID NO:5984)
3'-UAAAAACAUGUAAUGUGAUUUAAUAAU-5'(SEQ ID NO:2389)
KRAS-918靶:5'-ATTTTTGTACATTACACTAAATTATTA-3'(SEQ ID NO:3795)
5'-CACUAAAUUAUUAGCAUUUGUUUUA-3'(SEQ ID NO:5985)
3'-AUGUGAUUUAAUAAUCGUAAACAAAAU-5'(SEQ ID NO:2390)
KRAS-930靶:5'-TACACTAAATTATTAGCATTTGTTTTA-3'(SEQ ID NO:3796)
5'-CUAAAUUAUUAGCAUUUGUUUUAGC-3'(SEQ ID NO:5986)
3'-GUGAUUUAAUAAUCGUAAACAAAAUCG-5'(SEQ ID NO:2391)
KRAS-932靶:5'-CACTAAATTATTAGCATTTGTTTTAGC-3'(SEQ ID NO:3797)
5'-UAAAUUAUUAGCAUUUGUUUUAGCA-3'(SEQ ID NO:5987)
3'-UGAUUUAAUAAUCGUAAACAAAAUCGU-5'(SEQ ID NO:2392)
KRAS-933靶:5'-ACTAAATTATTAGCATTTGTTTTAGCA-3'(SEQ ID NO:3798)
5'-UAUUAGCAUUUGUUUUAGCAUUACC-3'(SEQ ID NO:5988)
3'-UAAUAAUCGUAAACAAAAUCGUAAUGG-5'(SEQ ID NO:2393)
KRAS-938靶:5'-ATTATTAGCATTTGTTTTAGCATTACC-3'(SEQ ID NO:3799)
5'-CAUUUGUUUUAGCAUUACCUAAUUU-3'(SEQ ID NO:5989)
3'-UCGUAAACAAAAUCGUAAUGGAUUAAA-5'(SEQ ID NO:2394)
KRAS-944靶:5'-AGCATTTGTTTTAGCATTACCTAATTT-3'(SEQ ID NO:3800)
5'-AUUUGUUUUAGCAUUACCUAAUUUU-3'(SEQ ID NO:5990)
3'-CGUAAACAAAAUCGUAAUGGAUUAAAA-5'(SEQ ID NO:2395)
KRAS-945靶:5'-GCATTTGTTTTAGCATTACCTAATTTT-3'(SEQ ID NO:3801)
5'-UUGUUUUAGCAUUACCUAAUUUUUU-3'(SEQ ID NO:5991)
3'-UAAACAAAAUCGUAAUGGAUUAAAAAA-5'(SEQ ID NO:2396)
KRAS-947靶:5'-ATTTGTTTTAGCATTACCTAATTTTTT-3'(SEQ ID NO:3802)
5'-UGUUUUAGCAUUACCUAAUUUUUUU-3'(SEQ ID NO:5992)
3'-AAACAAAAUCGUAAUGGAUUAAAAAAA-5'(SEQ ID NO:2397)
KRAS-948靶:5'-TTTGTTTTAGCATTACCTAATTTTTTT-3'(SEQ ID NO:3803)
5'-GUUUUAGCAUUACCUAAUUUUUUUC-3'(SEQ ID NO:5993)
3'-AACAAAAUCGUAAUGGAUUAAAAAAAG-5'(SEQ ID NO:2398)
KRAS-949靶:5'-TTGTTTTAGCATTACCTAATTTTTTTC-3'(SEQ ID NO:3804)
5'-UUUUAGCAUUACCUAAUUUUUUUCC-3'(SEQ ID NO:5994)
3'-ACAAAAUCGUAAUGGAUUAAAAAAAGG-5'(SEQ ID NO:2399)
KRAS-950靶:5'-TGTTTTAGCATTACCTAATTTTTTTCC-3'(SEQ ID NO:3805)
5'-GACUGUUAGCUUUUACCUUAAAUGC-3'(SEQ ID NO:5995)
3'-GUCUGACAAUCGAAAAUGGAAUUUACG-5'(SEQ ID NO:2400)
KRAS-986靶:5'-CAGACTGTTAGCTTTTACCTTAAATGC-3'(SEQ ID NO:3806)
5'-ACUGUUAGCUUUUACCUUAAAUGCU-3'(SEQ ID NO:5996)
3'-UCUGACAAUCGAAAAUGGAAUUUACGA-5'(SEQ ID NO:2401)
KRAS-987靶:5'-AGACTGTTAGCTTTTACCTTAAATGCT-3'(SEQ ID NO:3807)
5'-AGCUUUUACCUUAAAUGCUUAUUUU-3'(SEQ ID NO:5997)
3'-AAUCGAAAAUGGAAUUUACGAAUAAAA-5'(SEQ ID NO:2402)
KRAS-993靶:5'-TTAGCTTTTACCTTAAATGCTTATTTT-3'(SEQ ID NO:3808)
5'-GCUUUUACCUUAAAUGCUUAUUUUA-3'(SEQ ID NO:5998)
3'-AUCGAAAAUGGAAUUUACGAAUAAAAU-5'(SEQ ID NO:2403)
KRAS-994靶:5'-TAGCTTTTACCTTAAATGCTTATTTTA-3'(SEQ ID NO:3809)
5'-CUUUUACCUUAAAUGCUUAUUUUAA-3'(SEQ ID NO:5999)
3'-UCGAAAAUGGAAUUUACGAAUAAAAUU-5'(SEQ ID NO:2404)
KRAS-995靶:5'-AGCTTTTACCTTAAATGCTTATTTTAA-3'(SEQ ID NO:3810)
5'-CCUUAAAUGCUUAUUUUAAAAUGAC-3'(SEQ ID NO:6000)
3'-AUGGAAUUUACGAAUAAAAUUUUACUG-5'(SEQ ID NO:2405)
KRAS-1001靶:5'-TACCTTAAATGCTTATTTTAAAATGAC-3'(SEQ ID NO:3811)
5'-CUUAAAUGCUUAUUUUAAAAUGACA-3'(SEQ ID NO:6001)
3'-UGGAAUUUACGAAUAAAAUUUUACUGU-5'(SEQ ID NO:2406)
KRAS-1002靶:5'-ACCTTAAATGCTTATTTTAAAATGACA-3'(SEQ ID NO:3812)
5'-UGCUUAUUUUAAAAUGACAGUGGAA-3'(SEQ ID NO:6002)
3'-UUACGAAUAAAAUUUUACUGUCACCUU-5'(SEQ ID NO:2407)
KRAS-1008靶:5'-AATGCTTATTTTAAAATGACAGTGGAA-3'(SEQ ID NO:3813)
5'-CUUAUUUUAAAAUGACAGUGGAAGU-3'(SEQ ID NO:6003)
3'-ACGAAUAAAAUUUUACUGUCACCUUCA-5'(SEQ ID NO:2408)
KRAS-1010靶:5'-TGCTTATTTTAAAATGACAGTGGAAGT-3'(SEQ ID NO:3814)
5'-GUGGAAGUUUUUUUUUCCUCUAAGU-3'(SEQ ID NO:6004)
3'-GUCACCUUCAAAAAAAAAGGAGAUUCA-5'(SEQ ID NO:2409)
KRAS-1027靶:5'-CAGTGGAAGTTTTTTTTTCCTCTAAGT-3'(SEQ ID NO:3815)
5'-GGAAGUUUUUUUUUCCUCUAAGUGC-3'(SEQ ID NO:6005)
3'-CACCUUCAAAAAAAAAGGAGAUUCACG-5'(SEQ ID NO:2410)
KRAS-1029靶:5'-GTGGAAGTTTTTTTTTCCTCTAAGTGC-3'(SEQ ID NO:3816)
5'-GAAGUUUUUUUUUCCUCUAAGUGCC-3'(SEQ ID NO:6006)
3'-ACCUUCAAAAAAAAAGGAGAUUCACGG-5'(SEQ ID NO:2411)
KRAS-1030靶:5'-TGGAAGTTTTTTTTTCCTCTAAGTGCC-3'(SEQ ID NO:3817)
5'-UUUUGGUUUUUGAACUAGCAAUGCC-3'(SEQ ID NO:6007)
3'-UCAAAACCAAAAACUUGAUCGUUACGG-5'(SEQ ID NO:2412)
KRAS-1068靶:5'-AGTTTTGGTTTTTGAACTAGCAATGCC-3'(SEQ ID NO:3818)
5'-GCCUGUGAAAAAGAAACUGAAUACC-3'(SEQ ID NO:6008)
3'-UACGGACACUUUUUCUUUGACUUAUGG-5'(SEQ ID NO:2413)
KRAS-1090靶:5'-ATGCCTGTGAAAAAGAAACTGAATACC-3'(SEQ ID NO:3819)
5'-AAAAAGAAACUGAAUACCUAAGAUU-3'(SEQ ID NO:6009)
3'-ACUUUUUCUUUGACUUAUGGAUUCUAA-5'(SEQ ID NO:2414)
KRAS-1097靶:5'-TGAAAAAGAAACTGAATACCTAAGATT-3'(SEQ ID NO:3820)
5'-AAAAGAAACUGAAUACCUAAGAUUU-3'(SEQ ID NO:6010)
3'-CUUUUUCUUUGACUUAUGGAUUCUAAA-5'(SEQ ID NO:2415)
KRAS-1098靶:5'-GAAAAAGAAACTGAATACCTAAGATTT-3'(SEQ ID NO:3821)
5'-AACUGAAUACCUAAGAUUUCUGUCU-3'(SEQ ID NO:6011)
3'-CUUUGACUUAUGGAUUCUAAAGACAGA-5'(SEQ ID NO:2416)
KRAS-1104靶:5'-GAAACTGAATACCTAAGATTTCTGTCT-3'(SEQ ID NO:3822)
5'-UGCAGUUGAUUACUUCUUAUUUUUC-3'(SEQ ID NO:6012)
3'-GUACGUCAACUAAUGAAGAAUAAAAAG-5'(SEQ ID NO:2417)
KRAS-1145靶:5'-CATGCAGTTGATTACTTCTTATTTTTC-3'(SEQ ID NO:3823)
5'-GCAGUUGAUUACUUCUUAUUUUUCU-3'(SEQ ID NO:6013)
3'-UACGUCAACUAAUGAAGAAUAAAAAGA-5'(SEQ ID NO:2418)
KRAS-1146靶:5'-ATGCAGTTGATTACTTCTTATTTTTCT-3'(SEQ ID NO:3824)
5'-UUGAUUACUUCUUAUUUUUCUUACC-3'(SEQ ID NO:6014)
3'-UCAACUAAUGAAGAAUAAAAAGAAUGG-5'(SEQ ID NO:2419)
KRAS-1150靶:5'-AGTTGATTACTTCTTATTTTTCTTACC-3'(SEQ ID NO:3825)
5'-UUCUUAUUUUUCUUACCAAUUGUGA-3'(SEQ ID NO:6015)
3'-UGAAGAAUAAAAAGAAUGGUUAACACU-5'(SEQ ID NO:2420)
KRAS-1158靶:5'-ACTTCTTATTTTTCTTACCAATTGTGA-3'(SEQ ID NO:3826)
5'-UCUUAUUUUUCUUACCAAUUGUGAA-3'(SEQ ID NO:6016)
3'-GAAGAAUAAAAAGAAUGGUUAACACUU-5'(SEQ ID NO:2421)
KRAS-1159靶:5'-CTTCTTATTTTTCTTACCAATTGTGAA-3'(SEQ ID NO:3827)
5'-CUUAUUUUUCUUACCAAUUGUGAAU-3'(SEQ ID NO:6017)
3'-AAGAAUAAAAAGAAUGGUUAACACUUA-5'(SEQ ID NO:2422)
KRAS-1160靶:5'-TTCTTATTTTTCTTACCAATTGTGAAT-3'(SEQ ID NO:3828)
5'-AUGUUGGUGUGAAACAAAUUAAUGA-3'(SEQ ID NO:6018)
3'-CUUACAACCACACUUUGUUUAAUUACU-5'(SEQ ID NO:2423)
KRAS-1183靶:5'-GAATGTTGGTGTGAAACAAATTAATGA-3'(SEQ ID NO:3829)
5'-UUGGUGUGAAACAAAUUAAUGAAGC-3'(SEQ ID NO:6019)
3'-ACAACCACACUUUGUUUAAUUACUUCG-5'(SEQ ID NO:2424)
KRAS-1186靶:5'-TGTTGGTGTGAAACAAATTAATGAAGC-3'(SEQ ID NO:3830)
5'-UGGUGUGAAACAAAUUAAUGAAGCU-3'(SEQ ID NO:6020)
3'-CAACCACACUUUGUUUAAUUACUUCGA-5'(SEQ ID NO:2425)
KRAS-1187靶:5'-GTTGGTGTGAAACAAATTAATGAAGCT-3'(SEQ ID NO:3831)
5'-AACAAAUUAAUGAAGCUUUUGAAUC-3'(SEQ ID NO:6021)
3'-CUUUGUUUAAUUACUUCGAAAACUUAG-5'(SEQ ID NO:2426)
KRAS-1195靶:5'-GAAACAAATTAATGAAGCTTTTGAATC-3'(SEQ ID NO:3832)
5'-ACAAAUUAAUGAAGCUUUUGAAUCA-3'(SEQ ID NO:6022)
3'-UUUGUUUAAUUACUUCGAAAACUUAGU-5'(SEQ ID NO:2427)
KRAS-1196靶:5'-AAACAAATTAATGAAGCTTTTGAATCA-3'(SEQ ID NO:3833)
5'-UCUGUGUUUUAUCUAGUCACAUAAA-3'(SEQ ID NO:6023)
3'-UAAGACACAAAAUAGAUCAGUGUAUUU-5'(SEQ ID NO:2428)
KRAS-1228靶:5'-ATTCTGTGTTTTATCTAGTCACATAAA-3'(SEQ ID NO:3834)
5'-CUGUGUUUUAUCUAGUCACAUAAAU-3'(SEQ ID NO:6024)
3'-AAGACACAAAAUAGAUCAGUGUAUUUA-5'(SEQ ID NO:2429)
KRAS-1229靶:5'-TTCTGTGTTTTATCTAGTCACATAAAT-3'(SEQ ID NO:3835)
5'-UGUUUUAUCUAGUCACAUAAAUGGA-3'(SEQ ID NO:6025)
3'-ACACAAAAUAGAUCAGUGUAUUUACCU-5'(SEQ ID NO:2430)
KRAS-1232靶:5'-TGTGTTTTATCTAGTCACATAAATGGA-3'(SEQ ID NO:3836)
5'-GUUUUAUCUAGUCACAUAAAUGGAU-3'(SEQ ID NO:6026)
3'-CACAAAAUAGAUCAGUGUAUUUACCUA-5'(SEQ ID NO:2431)
KRAS-1233靶:5'-GTGTTTTATCTAGTCACATAAATGGAT-3'(SEQ ID NO:3837)
5'-AUCUAGUCACAUAAAUGGAUUAAUU-3'(SEQ ID NO:6027)
3'-AAUAGAUCAGUGUAUUUACCUAAUUAA-5'(SEQ ID NO:2432)
KRAS-1238靶:5'-TTATCTAGTCACATAAATGGATTAATT-3'(SEQ ID NO:3838)
5'-UCUAGUCACAUAAAUGGAUUAAUUA-3'(SEQ ID NO:6028)
3'-AUAGAUCAGUGUAUUUACCUAAUUAAU-5'(SEQ ID NO:2433)
KRAS-1239靶:5'-TATCTAGTCACATAAATGGATTAATTA-3'(SEQ ID NO:3839)
5'-CAUAAAUGGAUUAAUUACUAAUUUC-3'(SEQ ID NO:6029)
3'-GUGUAUUUACCUAAUUAAUGAUUAAAG-5'(SEQ ID NO:2434)
KRAS-1247靶:5'-CACATAAATGGATTAATTACTAATTTC-3'(SEQ ID NO:3840)
5'-AUAAAUGGAUUAAUUACUAAUUUCA-3'(SEQ ID NO:6030)
3'-UGUAUUUACCUAAUUAAUGAUUAAAGU-5'(SEQ ID NO:2435)
KRAS-1248靶:5'-ACATAAATGGATTAATTACTAATTTCA-3'(SEQ ID NO:3841)
5'-UGGAUUAAUUACUAAUUUCAGUUGA-3'(SEQ ID NO:6031)
3'-UUACCUAAUUAAUGAUUAAAGUCAACU-5'(SEQ ID NO:2436)
KRAS-1253靶:5'-AATGGATTAATTACTAATTTCAGTTGA-3'(SEQ ID NO:3842)
5'-GAUUAAUUACUAAUUUCAGUUGAGA-3'(SEQ ID NO:6032)
3'-ACCUAAUUAAUGAUUAAAGUCAACUCU-5'(SEQ ID NO:2437)
KRAS-1255靶:5'-TGGATTAATTACTAATTTCAGTTGAGA-3'(SEQ ID NO:3843)
5'-AUUAAUUACUAAUUUCAGUUGAGAC-3'(SEQ ID NO:6033)
3'-CCUAAUUAAUGAUUAAAGUCAACUCUG-5'(SEQ ID NO:2438)
KRAS-1256靶:5'-GGATTAATTACTAATTTCAGTTGAGAC-3'(SEQ ID NO:3844)
5'-UUAAUUACUAAUUUCAGUUGAGACC-3'(SEQ ID NO:6034)
3'-CUAAUUAAUGAUUAAAGUCAACUCUGG-5'(SEQ ID NO:2439)
KRAS-1257靶:5'-GATTAATTACTAATTTCAGTTGAGACC-3'(SEQ ID NO:3845)
5'-UAAUUGGUUUUUACUGAAACAUUGA-3'(SEQ ID NO:6035)
3'-AGAUUAACCAAAAAUGACUUUGUAACU-5'(SEQ ID NO:2440)
KRAS-1285靶:5'-TCTAATTGGTTTTTACTGAAACATTGA-3'(SEQ ID NO:3846)
5'-UGGUUUUUACUGAAACAUUGAGGGA-3'(SEQ ID NO:6036)
3'-UAACCAAAAAUGACUUUGUAACUCCCU-5'(SEQ ID NO:2441)
KRAS-1289靶:5'-ATTGGTTTTTACTGAAACATTGAGGGA-3'(SEQ ID NO:3847)
5'-GGUUUUUACUGAAACAUUGAGGGAA-3'(SEQ ID NO:6037)
3'-AACCAAAAAUGACUUUGUAACUCCCUU-5'(SEQ ID NO:2442)
KRAS-1290靶:5'-TTGGTTTTTACTGAAACATTGAGGGAA-3'(SEQ ID NO:3848)
5'-AUUGAGGGAACACAAAUUUAUGGGC-3'(SEQ ID NO:6038)
3'-UGUAACUCCCUUGUGUUUAAAUACCCG-5'(SEQ ID NO:2443)
KRAS-1305靶:5'-ACATTGAGGGAACACAAATTTATGGGC-3'(SEQ ID NO:3849)
5'-UUGAGGGAACACAAAUUUAUGGGCU-3'(SEQ ID NO:6039)
3'-GUAACUCCCUUGUGUUUAAAUACCCGA-5'(SEQ ID NO:2444)
KRAS-1306靶:5'-CATTGAGGGAACACAAATTTATGGGCT-3'(SEQ ID NO:3850)
5'-UGAUGAAUGUAAAGUUACACUGUUC-3'(SEQ ID NO:6040)
3'-GGACUACUUACAUUUCAAUGUGACAAG-5'(SEQ ID NO:2445)
KRAS-1379靶:5'-CCTGATGAATGTAAAGTTACACTGTTC-3'(SEQ ID NO:3851)
5'-GAUGAAUGUAAAGUUACACUGUUCA-3'(SEQ ID NO:6041)
3'-GACUACUUACAUUUCAAUGUGACAAGU-5'(SEQ ID NO:2446)
KRAS-1380靶:5'-CTGATGAATGTAAAGTTACACTGTTCA-3'(SEQ ID NO:3852)
5'-CCAAAAUAUUAUAUUUUUUCUAUAA-3'(SEQ ID NO:6042)
3'-GGGGUUUUAUAAUAUAAAAAAGAUAUU-5'(SEQ ID NO:2447)
KRAS-1452靶:5'-CCCCAAAATATTATATTTTTTCTATAA-3'(SEQ ID NO:3853)
5'-CAAAAUAUUAUAUUUUUUCUAUAAA-3'(SEQ ID NO:6043)
3'-GGGUUUUAUAAUAUAAAAAAGAUAUUU-5'(SEQ ID NO:2448)
KRAS-1453靶:5'-CCCAAAATATTATATTTTTTCTATAAA-3'(SEQ ID NO:3854)
5'-AAAAUAUUAUAUUUUUUCUAUAAAA-3'(SEQ ID NO:6044)
3'-GGUUUUAUAAUAUAAAAAAGAUAUUUU-5'(SEQ ID NO:2449)
KRAS-1454靶:5'-CCAAAATATTATATTTTTTCTATAAAA-3'(SEQ ID NO:3855)
5'-AAAUAUUAUAUUUUUUCUAUAAAAA-3'(SEQ ID NO:6045)
3'-GUUUUAUAAUAUAAAAAAGAUAUUUUU-5'(SEQ ID NO:2450)
KRAS-1455靶:5'-CAAAATATTATATTTTTTCTATAAAAA-3'(SEQ ID NO:3856)
5'-AUAUUAUAUUUUUUCUAUAAAAAGA-3'(SEQ ID NO:6046)
3'-UUUAUAAUAUAAAAAAGAUAUUUUUCU-5'(SEQ ID NO:2451)
KRAS-1457靶:5'-AAATATTATATTTTTTCTATAAAAAGA-3'(SEQ ID NO:3857)
5'-UAUUAUAUUUUUUCUAUAAAAAGAA-3'(SEQ ID NO:6047)
3'-UUAUAAUAUAAAAAAGAUAUUUUUCUU-5'(SEQ ID NO:2452)
KRAS-1458靶:5'-AATATTATATTTTTTCTATAAAAAGAA-3'(SEQ ID NO:3858)
5'-AUUAUAUUUUUUCUAUAAAAAGAAA-3'(SEQ ID NO:6048)
3'-UAUAAUAUAAAAAAGAUAUUUUUCUUU-5'(SEQ ID NO:2453)
KRAS-1459靶:5'-ATATTATATTTTTTCTATAAAAAGAAA-3'(SEQ ID NO:3859)
5'-UUAUAUUUUUUCUAUAAAAAGAAAA-3'(SEQ ID NO:6049)
3'-AUAAUAUAAAAAAGAUAUUUUUCUUUU-5'(SEQ ID NO:2454)
KRAS-1460靶:5'-TATTATATTTTTTCTATAAAAAGAAAA-3'(SEQ ID NO:3860)
5'-UAUAUUUUUUCUAUAAAAAGAAAAA-3'(SEQ ID NO:6050)
3'-UAAUAUAAAAAAGAUAUUUUUCUUUUU-5'(SEQ ID NO:2455)
KRAS-1461靶:5'-ATTATATTTTTTCTATAAAAAGAAAAA-3'(SEQ ID NO:3861)
5'-AUAUUUUUUCUAUAAAAAGAAAAAA-3'(SEQ ID NO:6051)
3'-AAUAUAAAAAAGAUAUUUUUCUUUUUU-5'(SEQ ID NO:2456)
KRAS-1462靶:5'-TTATATTTTTTCTATAAAAAGAAAAAA-3'(SEQ ID NO:3862)
5'-UAUUUUUUCUAUAAAAAGAAAAAAA-3'(SEQ ID NO:6052)
3'-AUAUAAAAAAGAUAUUUUUCUUUUUUU-5'(SEQ ID NO:2457)
KRAS-1463靶:5'-TATATTTTTTCTATAAAAAGAAAAAAA-3'(SEQ ID NO:3863)
5'-AUUUUUUCUAUAAAAAGAAAAAAAU-3'(SEQ ID NO:6053)
3'-UAUAAAAAAGAUAUUUUUCUUUUUUUA-5'(SEQ ID NO:2458)
KRAS-1464靶:5'-ATATTTTTTCTATAAAAAGAAAAAAAT-3'(SEQ ID NO:3864)
5'-UUCUAUAAAAAGAAAAAAAUGGAAA-3'(SEQ ID NO:6054)
3'-AAAAGAUAUUUUUCUUUUUUUACCUUU-5'(SEQ ID NO:2459)
KRAS-1469靶:5'-TTTTCTATAAAAAGAAAAAAATGGAAA-3'(SEQ ID NO:3865)
5'-UCUAUAAAAAGAAAAAAAUGGAAAA-3'(SEQ ID NO:6055)
3'-AAAGAUAUUUUUCUUUUUUUACCUUUU-5'(SEQ ID NO:2460)
KRAS-1470靶:5'-TTTCTATAAAAAGAAAAAAATGGAAAA-3'(SEQ ID NO:3866)
5'-UAUAAAAAGAAAAAAAUGGAAAAAA-3'(SEQ ID NO:6056)
3'-AGAUAUUUUUCUUUUUUUACCUUUUUU-5'(SEQ ID NO:2461)
KRAS-1472靶:5'-TCTATAAAAAGAAAAAAATGGAAAAAA-3'(SEQ ID NO:3867)
5'-AUAAAAAGAAAAAAAUGGAAAAAAA-3'(SEQ ID NO:6057)
3'-GAUAUUUUUCUUUUUUUACCUUUUUUU-5'(SEQ ID NO:2462)
KRAS-1473靶:5'-CTATAAAAAGAAAAAAATGGAAAAAAA-3'(SEQ ID NO:3868)
5'-UAAAAAGAAAAAAAUGGAAAAAAAU-3'(SEQ ID NO:6058)
3'-AUAUUUUUCUUUUUUUACCUUUUUUUA-5'(SEQ ID NO:2463)
KRAS-1474靶:5'-TATAAAAAGAAAAAAATGGAAAAAAAT-3'(SEQ ID NO:3869)
5'-AAAAAGAAAAAAAUGGAAAAAAAUU-3'(SEQ ID NO:6059)
3'-UAUUUUUCUUUUUUUACCUUUUUUUAA-5'(SEQ ID NO:2464)
KRAS-1475靶:5'-ATAAAAAGAAAAAAATGGAAAAAAATT-3'(SEQ ID NO:3870)
5'-AAAAGAAAAAAAUGGAAAAAAAUUA-3'(SEQ ID NO:6060)
3'-AUUUUUCUUUUUUUACCUUUUUUUAAU-5'(SEQ ID NO:2465)
KRAS-1476靶:5'-TAAAAAGAAAAAAATGGAAAAAAATTA-3'(SEQ ID NO:3871)
5'-AAAGAAAAAAAUGGAAAAAAAUUAC-3'(SEQ ID NO:6061)
3'-UUUUUCUUUUUUUACCUUUUUUUAAUG-5'(SEQ ID NO:2466)
KRAS-1477靶:5'-AAAAAGAAAAAAATGGAAAAAAATTAC-3'(SEQ ID NO:3872)
5'-AAGAAAAAAAUGGAAAAAAAUUACA-3'(SEQ ID NO:6062)
3'-UUUUCUUUUUUUACCUUUUUUUAAUGU-5'(SEQ ID NO:2467)
KRAS-1478靶:5'-AAAAGAAAAAAATGGAAAAAAATTACA-3'(SEQ ID NO:3873)
5'-AAAAAAUGGAAAAAAAUUACAAGGC-3'(SEQ ID NO:6063)
3'-CUUUUUUUACCUUUUUUUAAUGUUCCG-5'(SEQ ID NO:2468)
KRAS-1482靶:5'-GAAAAAAATGGAAAAAAATTACAAGGC-3'(SEQ ID NO:3874)
5'-AAAAAUGGAAAAAAAUUACAAGGCA-3'(SEQ ID NO:6064)
3'-UUUUUUUACCUUUUUUUAAUGUUCCGU-5'(SEQ ID NO:2469)
KRAS-1483靶:5'-AAAAAAATGGAAAAAAATTACAAGGCA-3'(SEQ ID NO:3875)
5'-UGGAAAAAAAUUACAAGGCAAUGGA-3'(SEQ ID NO:6065)
3'-UUACCUUUUUUUAAUGUUCCGUUACCU-5'(SEQ ID NO:2470)
KRAS-1488靶:5'-AATGGAAAAAAATTACAAGGCAATGGA-3'(SEQ ID NO:3876)
5'-GGAAAAAAAUUACAAGGCAAUGGAA-3'(SEQ ID NO:6066)
3'-UACCUUUUUUUAAUGUUCCGUUACCUU-5'(SEQ ID NO:2471)
KRAS-1489靶:5'-ATGGAAAAAAATTACAAGGCAATGGAA-3'(SEQ ID NO:3877)
5'-GAAAAAAAUUACAAGGCAAUGGAAA-3'(SEQ ID NO:6067)
3'-ACCUUUUUUUAAUGUUCCGUUACCUUU-5'(SEQ ID NO:2472)
KRAS-1490靶:5'-TGGAAAAAAATTACAAGGCAATGGAAA-3'(SEQ ID NO:3878)
5'-GCCAUUUCCUUUUCACAUUAGAUAA-3'(SEQ ID NO:6068)
3'-UCCGGUAAAGGAAAAGUGUAAUCUAUU-5'(SEQ ID NO:2473)
KRAS-1525靶:5'-AGGCCATTTCCTTTTCACATTAGATAA-3'(SEQ ID NO:3879)
5'-UCCUUUUCACAUUAGAUAAAUUACU-3'(SEQ ID NO:6069)
3'-AAAGGAAAAGUGUAAUCUAUUUAAUGA-5'(SEQ ID NO:2474)
KRAS-1531靶:5'-TTTCCTTTTCACATTAGATAAATTACT-3'(SEQ ID NO:3880)
5'-CACAUUAGAUAAAUUACUAUAAAGA-3'(SEQ ID NO:6070)
3'-AAGUGUAAUCUAUUUAAUGAUAUUUCU-5'(SEQ ID NO:2475)
KRAS-1538靶:5'-TTCACATTAGATAAATTACTATAAAGA-3'(SEQ ID NO:3881)
5'-ACAUUAGAUAAAUUACUAUAAAGAC-3'(SEQ ID NO:6071)
3'-AGUGUAAUCUAUUUAAUGAUAUUUCUG-5'(SEQ ID NO:2476)
KRAS-1539靶:5'-TCACATTAGATAAATTACTATAAAGAC-3'(SEQ ID NO:3882)
5'-CAUUAGAUAAAUUACUAUAAAGACU-3'(SEQ ID NO:6072)
3'-GUGUAAUCUAUUUAAUGAUAUUUCUGA-5'(SEQ ID NO:2477)
KRAS-1540靶:5'-CACATTAGATAAATTACTATAAAGACT-3'(SEQ ID NO:3883)
5'-AGUAUGAAAUGGGGAUUAUUAUAGC-3'(SEQ ID NO:6073)
3'-GGUCAUACUUUACCCCUAAUAAUAUCG-5'(SEQ ID NO:2478)
KRAS-1595靶:5'-CCAGTATGAAATGGGGATTATTATAGC-3'(SEQ ID NO:3884)
5'-UGGGGAUUAUUAUAGCAACCAUUUU-3'(SEQ ID NO:6074)
3'-UUACCCCUAAUAAUAUCGUUGGUAAAA-5'(SEQ ID NO:2479)
KRAS-1604靶:5'-AATGGGGATTATTATAGCAACCATTTT-3'(SEQ ID NO:3885)
5'-GGCUAUAUUUACAUGCUACUAAAUU-3'(SEQ ID NO:6075)
3'-CCCCGAUAUAAAUGUACGAUGAUUUAA-5'(SEQ ID NO:2480)
KRAS-1631靶:5'-GGGGCTATATTTACATGCTACTAAATT-3'(SEQ ID NO:3886)
5'-GCUAUAUUUACAUGCUACUAAAUUU-3'(SEQ ID NO:6076)
3'-CCCGAUAUAAAUGUACGAUGAUUUAAA-5'(SEQ ID NO:2481)
KRAS-1632靶:5'-GGGCTATATTTACATGCTACTAAATTT-3'(SEQ ID NO:3887)
5'-CUAUAUUUACAUGCUACUAAAUUUU-3'(SEQ ID NO:6077)
3'-CCGAUAUAAAUGUACGAUGAUUUAAAA-5'(SEQ ID NO:2482)
KRAS-1633靶:5'-GGCTATATTTACATGCTACTAAATTTT-3'(SEQ ID NO:3888)
5'-UAUAUUUACAUGCUACUAAAUUUUU-3'(SEQ ID NO:6078)
3'-CGAUAUAAAUGUACGAUGAUUUAAAAA-5'(SEQ ID NO:2483)
KRAS-1634靶:5'-GCTATATTTACATGCTACTAAATTTTT-3'(SEQ ID NO:3889)
5'-AUAUUUACAUGCUACUAAAUUUUUA-3'(SEQ ID NO:6079)
3'-GAUAUAAAUGUACGAUGAUUUAAAAAU-5'(SEQ ID NO:2484)
KRAS-1635靶:5'-CTATATTTACATGCTACTAAATTTTTA-3'(SEQ ID NO:3890)
5'-UACAUGCUACUAAAUUUUUAUAAUA-3'(SEQ ID NO:6080)
3'-AAAUGUACGAUGAUUUAAAAAUAUUAU-5'(SEQ ID NO:2485)
KRAS-1640靶:5'-TTTACATGCTACTAAATTTTTATAATA-3'(SEQ ID NO:3891)
5'-UACUAAAUUUUUAUAAUAAUUGAAA-3'(SEQ ID NO:6081)
3'-CGAUGAUUUAAAAAUAUUAUUAACUUU-5'(SEQ ID NO:2486)
KRAS-1647靶:5'-GCTACTAAATTTTTATAATAATTGAAA-3'(SEQ ID NO:3892)
5'-ACUAAAUUUUUAUAAUAAUUGAAAA-3'(SEQ ID NO:6082)
3'-GAUGAUUUAAAAAUAUUAUUAACUUUU-5'(SEQ ID NO:2487)
KRAS-1648靶:5'-CTACTAAATTTTTATAATAATTGAAAA-3'(SEQ ID NO:3893)
5'-UAAAUUUUUAUAAUAAUUGAAAAGA-3'(SEQ ID NO:6083)
3'-UGAUUUAAAAAUAUUAUUAACUUUUCU-5'(SEQ ID NO:2488)
KRAS-1650靶:5'-ACTAAATTTTTATAATAATTGAAAAGA-3'(SEQ ID NO:3894)
5'-AAAUUUUUAUAAUAAUUGAAAAGAU-3'(SEQ ID NO:6084)
3'-GAUUUAAAAAUAUUAUUAACUUUUCUA-5'(SEQ ID NO:2489)
KRAS-1651靶:5'-CTAAATTTTTATAATAATTGAAAAGAT-3'(SEQ ID NO:3895)
5'-AAUUUUUAUAAUAAUUGAAAAGAUU-3'(SEQ ID NO:6085)
3'-AUUUAAAAAUAUUAUUAACUUUUCUAA-5'(SEQ ID NO:2490)
KRAS-1652靶:5'-TAAATTTTTATAATAATTGAAAAGATT-3'(SEQ ID NO:3896)
5'-AUUUUUAUAAUAAUUGAAAAGAUUU-3'(SEQ ID NO:6086)
3'-UUUAAAAAUAUUAUUAACUUUUCUAAA-5'(SEQ ID NO:2491)
KRAS-1653靶:5'-AAATTTTTATAATAATTGAAAAGATTT-3'(SEQ ID NO:3897)
5'-UUUUUAUAAUAAUUGAAAAGAUUUU-3'(SEQ ID NO:6087)
3'-UUAAAAAUAUUAUUAACUUUUCUAAAA-5'(SEQ ID NO:2492)
KRAS-1654靶:5'-AATTTTTATAATAATTGAAAAGATTTT-3'(SEQ ID NO:3898)
5'-UUUUAUAAUAAUUGAAAAGAUUUUA-3'(SEQ ID NO:6088)
3'-UAAAAAUAUUAUUAACUUUUCUAAAAU-5'(SEQ ID NO:2493)
KRAS-1655靶:5'-ATTTTTATAATAATTGAAAAGATTTTA-3'(SEQ ID NO:3899)
5'-UUUAUAAUAAUUGAAAAGAUUUUAA-3'(SEQ ID NO:6089)
3'-AAAAAUAUUAUUAACUUUUCUAAAAUU-5'(SEQ ID NO:2494)
KRAS-1656靶:5'-TTTTTATAATAATTGAAAAGATTTTAA-3'(SEQ ID NO:3900)
5'-UUAUAAUAAUUGAAAAGAUUUUAAC-3'(SEQ ID NO:6090)
3'-AAAAUAUUAUUAACUUUUCUAAAAUUG-5'(SEQ ID NO:2495)
KRAS-1657靶:5'-TTTTATAATAATTGAAAAGATTTTAAC-3'(SEQ ID NO:3901)
5'-UAUAAUAAUUGAAAAGAUUUUAACA-3'(SEQ ID NO:6091)
3'-AAAUAUUAUUAACUUUUCUAAAAUUGU-5'(SEQ ID NO:2496)
KRAS-1658靶:5'-TTTATAATAATTGAAAAGATTTTAACA-3'(SEQ ID NO:3902)
5'-AUAAUUGAAAAGAUUUUAACAAGUA-3'(SEQ ID NO:6092)
3'-AUUAUUAACUUUUCUAAAAUUGUUCAU-5'(SEQ ID NO:2497)
KRAS-1662靶:5'-TAATAATTGAAAAGATTTTAACAAGTA-3'(SEQ ID NO:3903)
5'-UAAUUGAAAAGAUUUUAACAAGUAU-3'(SEQ ID NO:6093)
3'-UUAUUAACUUUUCUAAAAUUGUUCAUA-5'(SEQ ID NO:2498)
KRAS-1663靶:5'-AATAATTGAAAAGATTTTAACAAGTAT-3'(SEQ ID NO:3904)
5'-AUUGAAAAGAUUUUAACAAGUAUAA-3'(SEQ ID NO:6094)
3'-AUUAACUUUUCUAAAAUUGUUCAUAUU-5'(SEQ ID NO:2499)
KRAS-1665靶:5'-TAATTGAAAAGATTTTAACAAGTATAA-3'(SEQ ID NO:3905)
5'-UUGAAAAGAUUUUAACAAGUAUAAA-3'(SEQ ID NO:6095)
3'-UUAACUUUUCUAAAAUUGUUCAUAUUU-5'(SEQ ID NO:2500)
KRAS-1666靶:5'-AATTGAAAAGATTTTAACAAGTATAAA-3'(SEQ ID NO:3906)
5'-UGAAAAGAUUUUAACAAGUAUAAAA-3'(SEQ ID NO:6096)
3'-UAACUUUUCUAAAAUUGUUCAUAUUUU-5'(SEQ ID NO:2501)
KRAS-1667靶:5'-ATTGAAAAGATTTTAACAAGTATAAAA-3'(SEQ ID NO:3907)
5'-GAAAAGAUUUUAACAAGUAUAAAAA-3'(SEQ ID NO:6097)
3'-AACUUUUCUAAAAUUGUUCAUAUUUUU-5'(SEQ ID NO:2502)
KRAS-1668靶:5'-TTGAAAAGATTTTAACAAGTATAAAAA-3'(SEQ ID NO:3908)
5'-AAAAGAUUUUAACAAGUAUAAAAAA-3'(SEQ ID NO:6098)
3'-ACUUUUCUAAAAUUGUUCAUAUUUUUU-5'(SEQ ID NO:2503)
KRAS-1669靶:5'-TGAAAAGATTTTAACAAGTATAAAAAA-3'(SEQ ID NO:3909)
5'-AAAGAUUUUAACAAGUAUAAAAAAU-3'(SEQ ID NO:6099)
3'-CUUUUCUAAAAUUGUUCAUAUUUUUUA-5'(SEQ ID NO:2504)
KRAS-1670靶:5'-GAAAAGATTTTAACAAGTATAAAAAAT-3'(SEQ ID NO:3910)
5'-AAGAUUUUAACAAGUAUAAAAAAUU-3'(SEQ ID NO:6100)
3'-UUUUCUAAAAUUGUUCAUAUUUUUUAA-5'(SEQ ID NO:2505)
KRAS-1671靶:5'-AAAAGATTTTAACAAGTATAAAAAATT-3'(SEQ ID NO:3911)
5'-AGAUUUUAACAAGUAUAAAAAAUUC-3'(SEQ ID NO:6101)
3'-UUUCUAAAAUUGUUCAUAUUUUUUAAG-5'(SEQ ID NO:2506)
KRAS-1672靶:5'-AAAGATTTTAACAAGTATAAAAAATTC-3'(SEQ ID NO:3912)
5'-GAUUUUAACAAGUAUAAAAAAUUCU-3'(SEQ ID NO:6102)
3'-UUCUAAAAUUGUUCAUAUUUUUUAAGA-5'(SEQ ID NO:2507)
KRAS-1673靶:5'-AAGATTTTAACAAGTATAAAAAATTCT-3'(SEQ ID NO:3913)
5'-ACAAGUAUAAAAAAUUCUCAUAGGA-3'(SEQ ID NO:6103)
3'-AUUGUUCAUAUUUUUUAAGAGUAUCCU-5'(SEQ ID NO:2508)
KRAS-1680靶:5'-TAACAAGTATAAAAAATTCTCATAGGA-3'(SEQ ID NO:3914)
5'-CAAGUAUAAAAAAUUCUCAUAGGAA-3'(SEQ ID NO:6104)
3'-UUGUUCAUAUUUUUUAAGAGUAUCCUU-5'(SEQ ID NO:2509)
KRAS-1681靶:5'-AACAAGTATAAAAAATTCTCATAGGAA-3'(SEQ ID NO:3915)
5'-AAGUAUAAAAAAUUCUCAUAGGAAU-3'(SEQ ID NO:6105)
3'-UGUUCAUAUUUUUUAAGAGUAUCCUUA-5'(SEQ ID NO:2510)
KRAS-1682靶:5'-ACAAGTATAAAAAATTCTCATAGGAAT-3'(SEQ ID NO:3916)
5'-AGUAUAAAAAAUUCUCAUAGGAAUU-3'(SEQ ID NO:6106)
3'-GUUCAUAUUUUUUAAGAGUAUCCUUAA-5'(SEQ ID NO:2511)
KRAS-1683靶:5'-CAAGTATAAAAAATTCTCATAGGAATT-3'(SEQ ID NO:3917)
5'-GUAUAAAAAAUUCUCAUAGGAAUUA-3'(SEQ ID NO:6107)
3'-UUCAUAUUUUUUAAGAGUAUCCUUAAU-5'(SEQ ID NO:2512)
KRAS-1684靶:5'-AAGTATAAAAAATTCTCATAGGAATTA-3'(SEQ ID NO:3918)
5'-UAUAAAAAAUUCUCAUAGGAAUUAA-3'(SEQ ID NO:6108)
3'-UCAUAUUUUUUAAGAGUAUCCUUAAUU-5'(SEQ ID NO:2513)
KRAS-1685靶:5'-AGTATAAAAAATTCTCATAGGAATTAA-3'(SEQ ID NO:3919)
5'-AUAAAAAAUUCUCAUAGGAAUUAAA-3'(SEQ ID NO:6109)
3'-CAUAUUUUUUAAGAGUAUCCUUAAUUU-5'(SEQ ID NO:2514)
KRAS-1686靶:5'-GTATAAAAAATTCTCATAGGAATTAAA-3'(SEQ ID NO:3920)
5'-UAAAAAAUUCUCAUAGGAAUUAAAU-3'(SEQ ID NO:6110)
3'-AUAUUUUUUAAGAGUAUCCUUAAUUUA-5'(SEQ ID NO:2515)
KRAS-1687靶:5'-TATAAAAAATTCTCATAGGAATTAAAT-3'(SEQ ID NO:3921)
5'-AAAAAUUCUCAUAGGAAUUAAAUGU-3'(SEQ ID NO:6111)
3'-AUUUUUUAAGAGUAUCCUUAAUUUACA-5'(SEQ ID NO:2516)
KRAS-1689靶:5'-TAAAAAATTCTCATAGGAATTAAATGT-3'(SEQ ID NO:3922)
5'-AAAAUUCUCAUAGGAAUUAAAUGUA-3'(SEQ ID NO:6112)
3'-UUUUUUAAGAGUAUCCUUAAUUUACAU-5'(SEQ ID NO:2517)
KRAS-1690靶:5'-AAAAAATTCTCATAGGAATTAAATGTA-3'(SEQ ID NO:3923)
5'-CUCUUUCAUAGUAUAACUUUAAAUC-3'(SEQ ID NO:6113)
3'-ACGAGAAAGUAUCAUAUUGAAAUUUAG-5'(SEQ ID NO:2518)
KRAS-1734靶:5'-TGCTCTTTCATAGTATAACTTTAAATC-3'(SEQ ID NO:3924)
5'-UCAUAGUAUAACUUUAAAUCUUUUC-3'(SEQ ID NO:6114)
3'-AAAGUAUCAUAUUGAAAUUUAGAAAAG-5'(SEQ ID NO:2519)
KRAS-1739靶:5'-TTTCATAGTATAACTTTAAATCTTTTC-3'(SEQ ID NO:3925)
5'-CAUAGUAUAACUUUAAAUCUUUUCU-3'(SEQ ID NO:6115)
3'-AAGUAUCAUAUUGAAAUUUAGAAAAGA-5'(SEQ ID NO:2520)
KRAS-1740靶:5'-TTCATAGTATAACTTTAAATCTTTTCT-3'(SEQ ID NO:3926)
5'-UUUAAAUCUUUUCUUCAACUUGAGU-3'(SEQ ID NO:6116)
3'-UGAAAUUUAGAAAAGAAGUUGAACUCA-5'(SEQ ID NO:2521)
KRAS-1751靶:5'-ACTTTAAATCTTTTCTTCAACTTGAGT-3'(SEQ ID NO:3927)
5'-UUAAAUCUUUUCUUCAACUUGAGUC-3'(SEQ ID NO:6117)
3'-GAAAUUUAGAAAAGAAGUUGAACUCAG-5'(SEQ ID NO:2522)
KRAS-1752靶:5'-CTTTAAATCTTTTCTTCAACTTGAGTC-3'(SEQ ID NO:3928)
5'-AACUUGAGUCUUUGAAGAUAGUUUU-3'(SEQ ID NO:6118)
3'-AGUUGAACUCAGAAACUUCUAUCAAAA-5'(SEQ ID NO:2523)
KRAS-1767靶:5'-TCAACTTGAGTCTTTGAAGATAGTTTT-3'(SEQ ID NO:3929)
5'-CUUGAGUCUUUGAAGAUAGUUUUAA-3'(SEQ ID NO:6119)
3'-UUGAACUCAGAAACUUCUAUCAAAAUU-5'(SEQ ID NO:2524)
KRAS-1769靶:5'-AACTTGAGTCTTTGAAGATAGTTTTAA-3'(SEQ ID NO:3930)
5'-UUGAGUCUUUGAAGAUAGUUUUAAU-3'(SEQ ID NO:6120)
3'-UGAACUCAGAAACUUCUAUCAAAAUUA-5'(SEQ ID NO:2525)
KRAS-1770靶:5'-ACTTGAGTCTTTGAAGATAGTTTTAAT-3'(SEQ ID NO:3931)
5'-AAGAUAGUUUUAAUUCUGCUUGUGA-3'(SEQ ID NO:6121)
3'-ACUUCUAUCAAAAUUAAGACGAACACU-5'(SEQ ID NO:2526)
KRAS-1781靶:5'-TGAAGATAGTTTTAATTCTGCTTGTGA-3'(SEQ ID NO:3932)
5'-AGAUAGUUUUAAUUCUGCUUGUGAC-3'(SEQ ID NO:6122)
3'-CUUCUAUCAAAAUUAAGACGAACACUG-5'(SEQ ID NO:2527)
KRAS-1782靶:5'-GAAGATAGTTTTAATTCTGCTTGTGAC-3'(SEQ ID NO:3933)
5'-GAUAGUUUUAAUUCUGCUUGUGACA-3'(SEQ ID NO:6123)
3'-UUCUAUCAAAAUUAAGACGAACACUGU-5'(SEQ ID NO:2528)
KRAS-1783靶:5'-AAGATAGTTTTAATTCTGCTTGTGACA-3'(SEQ ID NO:3934)
5'-UGCUUGUGACAUUAAAAGAUUAUUU-3'(SEQ ID NO:6124)
3'-AGACGAACACUGUAAUUUUCUAAUAAA-5'(SEQ ID NO:2529)
KRAS-1797靶:5'-TCTGCTTGTGACATTAAAAGATTATTT-3'(SEQ ID NO:3935)
5'-AGCAUUGCUUUUGUUUCUUAAGAAA-3'(SEQ ID NO:6125)
3'-UCUCGUAACGAAAACAAAGAAUUCUUU-5'(SEQ ID NO:2530)
KRAS-2045靶:5'-AGAGCATTGCTTTTGTTTCTTAAGAAA-3'(SEQ ID NO:3936)
5'-GCAUUGCUUUUGUUUCUUAAGAAAA-3'(SEQ ID NO:6126)
3'-CUCGUAACGAAAACAAAGAAUUCUUUU-5'(SEQ ID NO:2531)
KRAS-2046靶:5'-GAGCATTGCTTTTGTTTCTTAAGAAAA-3'(SEQ ID NO:3937)
5'-CUUUUGUUUCUUAAGAAAACAAACU-3'(SEQ ID NO:6127)
3'-ACGAAAACAAAGAAUUCUUUUGUUUGA-5'(SEQ ID NO:2532)
KRAS-2052靶:5'-TGCTTTTGTTTCTTAAGAAAACAAACT-3'(SEQ ID NO:3938)
5'-UUCUUAAGAAAACAAACUCUUUUUU-3'(SEQ ID NO:6128)
3'-CAAAGAAUUCUUUUGUUUGAGAAAAAA-5'(SEQ ID NO:2533)
KRAS-2059靶:5'-GTTTCTTAAGAAAACAAACTCTTTTTT-3'(SEQ ID NO:3939)
5'-UCUUAAGAAAACAAACUCUUUUUUA-3'(SEQ ID NO:6129)
3'-AAAGAAUUCUUUUGUUUGAGAAAAAAU-5'(SEQ ID NO:2534)
KRAS-2060靶:5'-TTTCTTAAGAAAACAAACTCTTTTTTA-3'(SEQ ID NO:3940)
5'-CUUAAGAAAACAAACUCUUUUUUAA-3'(SEQ ID NO:6130)
3'-AAGAAUUCUUUUGUUUGAGAAAAAAUU-5'(SEQ ID NO:2535)
KRAS-2061靶:5'-TTCTTAAGAAAACAAACTCTTTTTTAA-3'(SEQ ID NO:3941)
5'-UUAAGAAAACAAACUCUUUUUUAAA-3'(SEQ ID NO:6131)
3'-AGAAUUCUUUUGUUUGAGAAAAAAUUU-5'(SEQ ID NO:2536)
KRAS-2062靶:5'-TCTTAAGAAAACAAACTCTTTTTTAAA-3'(SEQ ID NO:3942)
5'-UAAGAAAACAAACUCUUUUUUAAAA-3'(SEQ ID NO:6132)
3'-GAAUUCUUUUGUUUGAGAAAAAAUUUU-5'(SEQ ID NO:2537)
KRAS-2063靶:5'-CTTAAGAAAACAAACTCTTTTTTAAAA-3'(SEQ ID NO:3943)
5'-AAGAAAACAAACUCUUUUUUAAAAA-3'(SEQ ID NO:6133)
3'-AAUUCUUUUGUUUGAGAAAAAAUUUUU-5'(SEQ ID NO:2538)
KRAS-2064靶:5'-TTAAGAAAACAAACTCTTTTTTAAAAA-3'(SEQ ID NO:3944)
5'-AGAAAACAAACUCUUUUUUAAAAAU-3'(SEQ ID NO:6134)
3'-AUUCUUUUGUUUGAGAAAAAAUUUUUA-5'(SEQ ID NO:2539)
KRAS-2065靶:5'-TAAGAAAACAAACTCTTTTTTAAAAAT-3'(SEQ ID NO:3945)
5'-AACAAACUCUUUUUUAAAAAUUACU-3'(SEQ ID NO:6135)
3'-UUUUGUUUGAGAAAAAAUUUUUAAUGA-5'(SEQ ID NO:2540)
KRAS-2069靶:5'-AAAACAAACTCTTTTTTAAAAATTACT-3'(SEQ ID NO:3946)
5'-CUCUUUUUUAAAAAUUACUUUUAAA-3'(SEQ ID NO:6136)
3'-UUGAGAAAAAAUUUUUAAUGAAAAUUU-5'(SEQ ID NO:2541)
KRAS-2075靶:5'-AACTCTTTTTTAAAAATTACTTTTAAA-3'(SEQ ID NO:3947)
5'-UCUUUUUUAAAAAUUACUUUUAAAU-3'(SEQ ID NO:6137)
3'-UGAGAAAAAAUUUUUAAUGAAAAUUUA-5'(SEQ ID NO:2542)
KRAS-2076靶:5'-ACTCTTTTTTAAAAATTACTTTTAAAT-3'(SEQ ID NO:3948)
5'-CUUUUUUAAAAAUUACUUUUAAAUA-3'(SEQ ID NO:6138)
3'-GAGAAAAAAUUUUUAAUGAAAAUUUAU-5'(SEQ ID NO:2543)
KRAS-2077靶:5'-CTCTTTTTTAAAAATTACTTTTAAATA-3'(SEQ ID NO:3949)
5'-UUUUUUAAAAAUUACUUUUAAAUAU-3'(SEQ ID NO:6139)
3'-AGAAAAAAUUUUUAAUGAAAAUUUAUA-5'(SEQ ID NO:2544)
KRAS-2078靶:5'-TCTTTTTTAAAAATTACTTTTAAATAT-3'(SEQ ID NO:3950)
5'-UUUUUAAAAAUUACUUUUAAAUAUU-3'(SEQ ID NO:6140)
3'-GAAAAAAUUUUUAAUGAAAAUUUAUAA-5'(SEQ ID NO:2545)
KRAS-2079靶:5'-CTTTTTTAAAAATTACTTTTAAATATT-3'(SEQ ID NO:3951)
5'-UUUUAAAAAUUACUUUUAAAUAUUA-3'(SEQ ID NO:6141)
3'-AAAAAAUUUUUAAUGAAAAUUUAUAAU-5'(SEQ ID NO:2546)
KRAS-2080靶:5'-TTTTTTAAAAATTACTTTTAAATATTA-3'(SEQ ID NO:3952)
5'-UUUAAAAAUUACUUUUAAAUAUUAA-3'(SEQ ID NO:6142)
3'-AAAAAUUUUUAAUGAAAAUUUAUAAUU-5'(SEQ ID NO:2547)
KRAS-2081靶:5'-TTTTTAAAAATTACTTTTAAATATTAA-3'(SEQ ID NO:3953)
5'-UUAAAAAUUACUUUUAAAUAUUAAC-3'(SEQ ID NO:6143)
3'-AAAAUUUUUAAUGAAAAUUUAUAAUUG-5'(SEQ ID NO:2548)
KRAS-2082靶:5'-TTTTAAAAATTACTTTTAAATATTAAC-3'(SEQ ID NO:3954)
5'-UAAAAAUUACUUUUAAAUAUUAACU-3'(SEQ ID NO:6144)
3'-AAAUUUUUAAUGAAAAUUUAUAAUUGA-5'(SEQ ID NO:2549)
KRAS-2083靶:5'-TTTAAAAATTACTTTTAAATATTAACT-3'(SEQ ID NO:3955)
5'-UACUUUUAAAUAUUAACUCAAAAGU-3'(SEQ ID NO:6145)
3'-UAAUGAAAAUUUAUAAUUGAGUUUUCA-5'(SEQ ID NO:2550)
KRAS-2090靶:5'-ATTACTTTTAAATATTAACTCAAAAGT-3'(SEQ ID NO:3956)
5'-ACUUUUAAAUAUUAACUCAAAAGUU-3'(SEQ ID NO:6146)
3'-AAUGAAAAUUUAUAAUUGAGUUUUCAA-5'(SEQ ID NO:2551)
KRAS-2091靶:5'-TTACTTTTAAATATTAACTCAAAAGTT-3'(SEQ ID NO:3957)
5'-UUUUAAAUAUUAACUCAAAAGUUGA-3'(SEQ ID NO:6147)
3'-UGAAAAUUUAUAAUUGAGUUUUCAACU-5'(SEQ ID NO:2552)
KRAS-2093靶:5'-ACTTTTAAATATTAACTCAAAAGTTGA-3'(SEQ ID NO:3958)
5'-UUAAAUAUUAACUCAAAAGUUGAGA-3'(SEQ ID NO:6148)
3'-AAAAUUUAUAAUUGAGUUUUCAACUCU-5'(SEQ ID NO:2553)
KRAS-2095靶:5'-TTTTAAATATTAACTCAAAAGTTGAGA-3'(SEQ ID NO:3959)
5'-UAAAUAUUAACUCAAAAGUUGAGAU-3'(SEQ ID NO:6149)
3'-AAAUUUAUAAUUGAGUUUUCAACUCUA-5'(SEQ ID NO:2554)
KRAS-2096靶:5'-TTTAAATATTAACTCAAAAGTTGAGAT-3'(SEQ ID NO:3960)
5'-AAAUAUUAACUCAAAAGUUGAGAUU-3'(SEQ ID NO:6150)
3'-AAUUUAUAAUUGAGUUUUCAACUCUAA-5'(SEQ ID NO:2555)
KRAS-2097靶:5'-TTAAATATTAACTCAAAAGTTGAGATT-3'(SEQ ID NO:3961)
5'-AAUAUUAACUCAAAAGUUGAGAUUU-3'(SEQ ID NO:6151)
3'-AUUUAUAAUUGAGUUUUCAACUCUAAA-5'(SEQ ID NO:2556)
KRAS-2098靶:5'-TAAATATTAACTCAAAAGTTGAGATTT-3'(SEQ ID NO:3962)
5'-GGUGUGCCAAGACAUUAAUUUUUUU-3'(SEQ ID NO:6152)
3'-CACCACACGGUUCUGUAAUUAAAAAAA-5'(SEQ ID NO:2557)
KRAS-2132靶:5'-GTGGTGTGCCAAGACATTAATTTTTTT-3'(SEQ ID NO:3963)
5'-GCCAAGACAUUAAUUUUUUUUUUAA-3'(SEQ ID NO:6153)
3'-CACGGUUCUGUAAUUAAAAAAAAAAUU-5'(SEQ ID NO:2558)
KRAS-2137靶:5'-GTGCCAAGACATTAATTTTTTTTTTAA-3'(SEQ ID NO:3964)
5'-CCAAGACAUUAAUUUUUUUUUUAAA-3'(SEQ ID NO:6154)
3'-ACGGUUCUGUAAUUAAAAAAAAAAUUU-5'(SEQ ID NO:2559)
KRAS-2138靶:5'-TGCCAAGACATTAATTTTTTTTTTAAA-3'(SEQ ID NO:3965)
5'-CAUUAAUUUUUUUUUUAAACAAUGA-3'(SEQ ID NO:6155)
3'-CUGUAAUUAAAAAAAAAAUUUGUUACU-5'(SEQ ID NO:2560)
KRAS-2144靶:5'-GACATTAATTTTTTTTTTAAACAATGA-3'(SEQ ID NO:3966)
5'-AUUAAUUUUUUUUUUAAACAAUGAA-3'(SEQ ID NO:6156)
3'-UGUAAUUAAAAAAAAAAUUUGUUACUU-5'(SEQ ID NO:2561)
KRAS-2145靶:5'-ACATTAATTTTTTTTTTAAACAATGAA-3'(SEQ ID NO:3967)
5'-UAAUUUUUUUUUUAAACAAUGAAGU-3'(SEQ ID NO:6157)
3'-UAAUUAAAAAAAAAAUUUGUUACUUCA-5'(SEQ ID NO:2562)
KRAS-2147靶:5'-ATTAATTTTTTTTTTAAACAATGAAGT-3'(SEQ ID NO:3968)
5'-AUUUUUUUUUUAAACAAUGAAGUGA-3'(SEQ ID NO:6158)
3'-AUUAAAAAAAAAAUUUGUUACUUCACU-5'(SEQ ID NO:2563)
KRAS-2149靶:5'-TAATTTTTTTTTTAAACAATGAAGTGA-3'(SEQ ID NO:3969)
5'-UUUUUUUUUUAAACAAUGAAGUGAA-3'(SEQ ID NO:6159)
3'-UUAAAAAAAAAAUUUGUUACUUCACUU-5'(SEQ ID NO:2564)
KRAS-2150靶:5'-AATTTTTTTTTTAAACAATGAAGTGAA-3'(SEQ ID NO:3970)
5'-UUUUUUUUUAAACAAUGAAGUGAAA-3'(SEQ ID NO:6160)
3'-UAAAAAAAAAAUUUGUUACUUCACUUU-5'(SEQ ID NO:2565)
KRAS-2151靶:5'-ATTTTTTTTTTAAACAATGAAGTGAAA-3'(SEQ ID NO:3971)
5'-UUUUUUUUAAACAAUGAAGUGAAAA-3'(SEQ ID NO:6161)
3'-AAAAAAAAAAUUUGUUACUUCACUUUU-5'(SEQ ID NO:2566)
KRAS-2152靶:5'-TTTTTTTTTTAAACAATGAAGTGAAAA-3'(SEQ ID NO:3972)
5'-UUUUUUUAAACAAUGAAGUGAAAAA-3'(SEQ ID NO:6162)
3'-AAAAAAAAAUUUGUUACUUCACUUUUU-5'(SEQ ID NO:2567)
KRAS-2153靶:5'-TTTTTTTTTAAACAATGAAGTGAAAAA-3'(SEQ ID NO:3973)
5'-UUUUUAAACAAUGAAGUGAAAAAGU-3'(SEQ ID NO:6163)
3'-AAAAAAAUUUGUUACUUCACUUUUUCA-5'(SEQ ID NO:2568)
KRAS-2155靶:5'-TTTTTTTAAACAATGAAGTGAAAAAGT-3'(SEQ ID NO:3974)
5'-UUUUAAACAAUGAAGUGAAAAAGUU-3'(SEQ ID NO:6164)
3'-AAAAAAUUUGUUACUUCACUUUUUCAA-5'(SEQ ID NO:2569)
KRAS-2156靶:5'-TTTTTTAAACAATGAAGTGAAAAAGTT-3'(SEQ ID NO:3975)
5'-UUUAAACAAUGAAGUGAAAAAGUUU-3'(SEQ ID NO:6165)
3'-AAAAAUUUGUUACUUCACUUUUUCAAA-5'(SEQ ID NO:2570)
KRAS-2157靶:5'-TTTTTAAACAATGAAGTGAAAAAGTTT-3'(SEQ ID NO:3976)
5'-AUGAAGUGAAAAAGUUUUACAAUCU-3'(SEQ ID NO:6166)
3'-GUUACUUCACUUUUUCAAAAUGUUAGA-5'(SEQ ID NO:2571)
KRAS-2165靶:5'-CAATGAAGTGAAAAAGTTTTACAATCT-3'(SEQ ID NO:3977)
5'-UGAAAAAGUUUUACAAUCUCUAGGU-3'(SEQ ID NO:6167)
3'-UCACUUUUUCAAAAUGUUAGAGAUCCA-5'(SEQ ID NO:2572)
KRAS-2171靶:5'-AGTGAAAAAGTTTTACAATCTCTAGGT-3'(SEQ ID NO:3978)
5'-GAAAAAGUUUUACAAUCUCUAGGUU-3'(SEQ ID NO:6168)
3'-CACUUUUUCAAAAUGUUAGAGAUCCAA-5'(SEQ ID NO:2573)
KRAS-2172靶:5'-GTGAAAAAGTTTTACAATCTCTAGGTT-3'(SEQ ID NO:3979)
5'-AAAAAGUUUUACAAUCUCUAGGUUU-3'(SEQ ID NO:6169)
3'-ACUUUUUCAAAAUGUUAGAGAUCCAAA-5'(SEQ ID NO:2574)
KRAS-2173靶:5'-TGAAAAAGTTTTACAATCTCTAGGTTT-3'(SEQ ID NO:3980)
5'-ACUGGUUAAAUUAACAUUGCAUAAA-3'(SEQ ID NO:6170)
3'-UGUGACCAAUUUAAUUGUAACGUAUUU-5'(SEQ ID NO:2575)
KRAS-2214靶:5'-ACACTGGTTAAATTAACATTGCATAAA-3'(SEQ ID NO:3981)
5'-CUGGUUAAAUUAACAUUGCAUAAAC-3'(SEQ ID NO:6171)
3'-GUGACCAAUUUAAUUGUAACGUAUUUG-5'(SEQ ID NO:2576)
KRAS-2215靶:5'-CACTGGTTAAATTAACATTGCATAAAC-3'(SEQ ID NO:3982)
5'-UGGUUAAAUUAACAUUGCAUAAACA-3'(SEQ ID NO:6172)
3'-UGACCAAUUUAAUUGUAACGUAUUUGU-5'(SEQ ID NO:2577)
KRAS-2216靶:5'-ACTGGTTAAATTAACATTGCATAAACA-3'(SEQ ID NO:3983)
5'-ACAUUGCAUAAACACUUUUCAAGUC-3'(SEQ ID NO:6173)
3'-AUUGUAACGUAUUUGUGAAAAGUUCAG-5'(SEQ ID NO:2578)
KRAS-2227靶:5'-TAACATTGCATAAACACTTTTCAAGTC-3'(SEQ ID NO:3984)
5'-UCAAGUCUGAUCCAUAUUUAAUAAU-3'(SEQ ID NO:6174)
3'-AAAGUUCAGACUAGGUAUAAAUUAUUA-5'(SEQ ID NO:2579)
KRAS-2245靶:5'-TTTCAAGTCTGATCCATATTTAATAAT-3'(SEQ ID NO:3985)
5'-UCCAUAUUUAAUAAUGCUUUAAAAU-3'(SEQ ID NO:6175)
3'-CUAGGUAUAAAUUAUUACGAAAUUUUA-5'(SEQ ID NO:2580)
KRAS-2255靶:5'-GATCCATATTTAATAATGCTTTAAAAT-3'(SEQ ID NO:3986)
5'-CCAUAUUUAAUAAUGCUUUAAAAUA-3'(SEQ ID NO:6176)
3'-UAGGUAUAAAUUAUUACGAAAUUUUAU-5'(SEQ ID NO:2581)
KRAS-2256靶:5'-ATCCATATTTAATAATGCTTTAAAATA-3'(SEQ ID NO:3987)
5'-CAUAUUUAAUAAUGCUUUAAAAUAA-3'(SEQ ID NO:6177)
3'-AGGUAUAAAUUAUUACGAAAUUUUAUU-5'(SEQ ID NO:2582)
KRAS-2257靶:5'-TCCATATTTAATAATGCTTTAAAATAA-3'(SEQ ID NO:3988)
5'-AUAUUUAAUAAUGCUUUAAAAUAAA-3'(SEQ ID NO:6178)
3'-GGUAUAAAUUAUUACGAAAUUUUAUUU-5'(SEQ ID NO:2583)
KRAS-2258靶:5'-CCATATTTAATAATGCTTTAAAATAAA-3'(SEQ ID NO:3989)
5'-UAUUUAAUAAUGCUUUAAAAUAAAA-3'(SEQ ID NO:6179)
3'-GUAUAAAUUAUUACGAAAUUUUAUUUU-5'(SEQ ID NO:2584)
KRAS-2259靶:5'-CATATTTAATAATGCTTTAAAATAAAA-3'(SEQ ID NO:3990)
5'-AUUUAAUAAUGCUUUAAAAUAAAAA-3'(SEQ ID NO:6180)
3'-UAUAAAUUAUUACGAAAUUUUAUUUUU-5'(SEQ ID NO:2585)
KRAS-2260靶:5'-ATATTTAATAATGCTTTAAAATAAAAA-3'(SEQ ID NO:3991)
5'-UUAAUAAUGCUUUAAAAUAAAAAUA-3'(SEQ ID NO:6181)
3'-UAAAUUAUUACGAAAUUUUAUUUUUAU-5'(SEQ ID NO:2586)
KRAS-2262靶:5'-ATTTAATAATGCTTTAAAATAAAAATA-3'(SEQ ID NO:3992)
5'-UAAUAAUGCUUUAAAAUAAAAAUAA-3'(SEQ ID NO:6182)
3'-AAAUUAUUACGAAAUUUUAUUUUUAUU-5'(SEQ ID NO:2587)
KRAS-2263靶:5'-TTTAATAATGCTTTAAAATAAAAATAA-3'(SEQ ID NO:3993)
5'-AAUAAUGCUUUAAAAUAAAAAUAAA-3'(SEQ ID NO:6183)
3'-AAUUAUUACGAAAUUUUAUUUUUAUUU-5'(SEQ ID NO:2588)
KRAS-2264靶:5'-TTAATAATGCTTTAAAATAAAAATAAA-3'(SEQ ID NO:3994)
5'-AUAAUGCUUUAAAAUAAAAAUAAAA-3'(SEQ ID NO:6184)
3'-AUUAUUACGAAAUUUUAUUUUUAUUUU-5'(SEQ ID NO:2589)
KRAS-2265靶:5'-TAATAATGCTTTAAAATAAAAATAAAA-3'(SEQ ID NO:3995)
5'-UUUAAAAUAAAAAUAAAAACAAUCC-3'(SEQ ID NO:6185)
3'-CGAAAUUUUAUUUUUAUUUUUGUUAGG-5'(SEQ ID NO:2590)
KRAS-2272靶:5'-GCTTTAAAATAAAAATAAAAACAATCC-3'(SEQ ID NO:3996)
5'-AUAAAAAUAAAAACAAUCCUUUUGA-3'(SEQ ID NO:6186)
3'-UUUAUUUUUAUUUUUGUUAGGAAAACU-5'(SEQ ID NO:2591)
KRAS-2278靶:5'-AAATAAAAATAAAAACAATCCTTTTGA-3'(SEQ ID NO:3997)
5'-UAAAAAUAAAAACAAUCCUUUUGAU-3'(SEQ ID NO:6187)
3'-UUAUUUUUAUUUUUGUUAGGAAAACUA-5'(SEQ ID NO:2592)
KRAS-2279靶:5'-AATAAAAATAAAAACAATCCTTTTGAT-3'(SEQ ID NO:3998)
5'-AAAAAUAAAAACAAUCCUUUUGAUA-3'(SEQ ID NO:6188)
3'-UAUUUUUAUUUUUGUUAGGAAAACUAU-5'(SEQ ID NO:2593)
KRAS-2280靶:5'-ATAAAAATAAAAACAATCCTTTTGATA-3'(SEQ ID NO:3999)
5'-AAAAUAAAAACAAUCCUUUUGAUAA-3'(SEQ ID NO:6189)
3'-AUUUUUAUUUUUGUUAGGAAAACUAUU-5'(SEQ ID NO:2594)
KRAS-2281靶:5'-TAAAAATAAAAACAATCCTTTTGATAA-3'(SEQ ID NO:4000)
5'-AAAUAAAAACAAUCCUUUUGAUAAA-3'(SEQ ID NO:6190)
3'-UUUUUAUUUUUGUUAGGAAAACUAUUU-5'(SEQ ID NO:2595)
KRAS-2282靶:5'-AAAAATAAAAACAATCCTTTTGATAAA-3'(SEQ ID NO:4001)
5'-AAUAAAAACAAUCCUUUUGAUAAAU-3'(SEQ ID NO:6191)
3'-UUUUAUUUUUGUUAGGAAAACUAUUUA-5'(SEQ ID NO:2596)
KRAS-2283靶:5'-AAAATAAAAACAATCCTTTTGATAAAT-3'(SEQ ID NO:4002)
5'-AUAAAAACAAUCCUUUUGAUAAAUU-3'(SEQ ID NO:6192)
3'-UUUAUUUUUGUUAGGAAAACUAUUUAA-5'(SEQ ID NO:2597)
KRAS-2284靶:5'-AAATAAAAACAATCCTTTTGATAAATT-3'(SEQ ID NO:4003)
5'-UAAAAACAAUCCUUUUGAUAAAUUU-3'(SEQ ID NO:6193)
3'-UUAUUUUUGUUAGGAAAACUAUUUAAA-5'(SEQ ID NO:2598)
KRAS-2285靶:5'-AATAAAAACAATCCTTTTGATAAATTT-3'(SEQ ID NO:4004)
5'-AACAAUCCUUUUGAUAAAUUUAAAA-3'(SEQ ID NO:6194)
3'-UUUUGUUAGGAAAACUAUUUAAAUUUU-5'(SEQ ID NO:2599)
KRAS-2289靶:5'-AAAACAATCCTTTTGATAAATTTAAAA-3'(SEQ ID NO:4005)
5'-UCCUUUUGAUAAAUUUAAAAUGUUA-3'(SEQ ID NO:6195)
3'-UUAGGAAAACUAUUUAAAUUUUACAAU-5'(SEQ ID NO:2600)
KRAS-2294靶:5'-AATCCTTTTGATAAATTTAAAATGTTA-3'(SEQ ID NO:4006)
5'-CCUUUUGAUAAAUUUAAAAUGUUAC-3'(SEQ ID NO:6196)
3'-UAGGAAAACUAUUUAAAUUUUACAAUG-5'(SEQ ID NO:2601)
KRAS-2295靶:5'-ATCCTTTTGATAAATTTAAAATGTTAC-3'(SEQ ID NO:4007)
5'-CUUUUGAUAAAUUUAAAAUGUUACU-3'(SEQ ID NO:6197)
3'-AGGAAAACUAUUUAAAUUUUACAAUGA-5'(SEQ ID NO:2602)
KRAS-2296靶:5'-TCCTTTTGATAAATTTAAAATGTTACT-3'(SEQ ID NO:4008)
5'-UGAUAAAUUUAAAAUGUUACUUAUU-3'(SEQ ID NO:6198)
3'-AAACUAUUUAAAUUUUACAAUGAAUAA-5'(SEQ ID NO:2603)
KRAS-2300靶:5'-TTTGATAAATTTAAAATGTTACTTATT-3'(SEQ ID NO:4009)
5'-GAUAAAUUUAAAAUGUUACUUAUUU-3'(SEQ ID NO:6199)
3'-AACUAUUUAAAUUUUACAAUGAAUAAA-5'(SEQ ID NO:2604)
KRAS-2301靶:5'-TTGATAAATTTAAAATGTTACTTATTT-3'(SEQ ID NO:4010)
5'-AUAAAUUUAAAAUGUUACUUAUUUU-3'(SEQ ID NO:6200)
3'-ACUAUUUAAAUUUUACAAUGAAUAAAA-5'(SEQ ID NO:2605)
KRAS-2302靶:5'-TGATAAATTTAAAATGTTACTTATTTT-3'(SEQ ID NO:4011)
5'-UAAAUUUAAAAUGUUACUUAUUUUA-3'(SEQ ID NO:6201)
3'-CUAUUUAAAUUUUACAAUGAAUAAAAU-5'(SEQ ID NO:2606)
KRAS-2303靶:5'-GATAAATTTAAAATGTTACTTATTTTA-3'(SEQ ID NO:4012)
5'-AAAUUUAAAAUGUUACUUAUUUUAA-3'(SEQ ID NO:6202)
3'-UAUUUAAAUUUUACAAUGAAUAAAAUU-5'(SEQ ID NO:2607)
KRAS-2304靶:5'-ATAAATTTAAAATGTTACTTATTTTAA-3'(SEQ ID NO:4013)
5'-AAUUUAAAAUGUUACUUAUUUUAAA-3'(SEQ ID NO:6203)
3'-AUUUAAAUUUUACAAUGAAUAAAAUUU-5'(SEQ ID NO:2608)
KRAS-2305靶:5'-TAAATTTAAAATGTTACTTATTTTAAA-3'(SEQ ID NO:4014)
5'-UUUAAAAUGUUACUUAUUUUAAAAU-3'(SEQ ID NO:6204)
3'-UUAAAUUUUACAAUGAAUAAAAUUUUA-5'(SEQ ID NO:2609)
KRAS-2307靶:5'-AATTTAAAATGTTACTTATTTTAAAAT-3'(SEQ ID NO:4015)
5'-UUAAAAUGUUACUUAUUUUAAAAUA-3'(SEQ ID NO:6205)
3'-UAAAUUUUACAAUGAAUAAAAUUUUAU-5'(SEQ ID NO:2610)
KRAS-2308靶:5'-ATTTAAAATGTTACTTATTTTAAAATA-3'(SEQ ID NO:4016)
5'-UAAAAUGUUACUUAUUUUAAAAUAA-3'(SEQ ID NO:6206)
3'-AAAUUUUACAAUGAAUAAAAUUUUAUU-5'(SEQ ID NO:2611)
KRAS-2309靶:5'-TTTAAAATGTTACTTATTTTAAAATAA-3'(SEQ ID NO:4017)
5'-AAAAUGUUACUUAUUUUAAAAUAAA-3'(SEQ ID NO:6207)
3'-AAUUUUACAAUGAAUAAAAUUUUAUUU-5'(SEQ ID NO:2612)
KRAS-2310靶:5'-TTAAAATGTTACTTATTTTAAAATAAA-3'(SEQ ID NO:4018)
5'-AAAUGUUACUUAUUUUAAAAUAAAU-3'(SEQ ID NO:6208)
3'-AUUUUACAAUGAAUAAAAUUUUAUUUA-5'(SEQ ID NO:2613)
KRAS-2311靶:5'-TAAAATGTTACTTATTTTAAAATAAAT-3'(SEQ ID NO:4019)
5'-AUGUUACUUAUUUUAAAAUAAAUGA-3'(SEQ ID NO:6209)
3'-UUUACAAUGAAUAAAAUUUUAUUUACU-5'(SEQ ID NO:2614)
KRAS-2313靶:5'-AAATGTTACTTATTTTAAAATAAATGA-3'(SEQ ID NO:4020)
5'-ACUUAUUUUAAAAUAAAUGAAGUGA-3'(SEQ ID NO:6210)
3'-AAUGAAUAAAAUUUUAUUUACUUCACU-5'(SEQ ID NO:2615)
KRAS-2318靶:5'-TTACTTATTTTAAAATAAATGAAGTGA-3'(SEQ ID NO:4021)
5'-UUAUUUUAAAAUAAAUGAAGUGAGA-3'(SEQ ID NO:6211)
3'-UGAAUAAAAUUUUAUUUACUUCACUCU-5'(SEQ ID NO:2616)
KRAS-2320靶:5'-ACTTATTTTAAAATAAATGAAGTGAGA-3'(SEQ ID NO:4022)
5'-UAUUUUAAAAUAAAUGAAGUGAGAU-3'(SEQ ID NO:6212)
3'-GAAUAAAAUUUUAUUUACUUCACUCUA-5'(SEQ ID NO:2617)
KRAS-2321靶:5'-CTTATTTTAAAATAAATGAAGTGAGAT-3'(SEQ ID NO:4023)
5'-UUUAAAAUAAAUGAAGUGAGAUGGC-3'(SEQ ID NO:6213)
3'-UAAAAUUUUAUUUACUUCACUCUACCG-5'(SEQ ID NO:2618)
KRAS-2324靶:5'-ATTTTAAAATAAATGAAGTGAGATGGC-3'(SEQ ID NO:4024)
5'-UUAAAAUAAAUGAAGUGAGAUGGCA-3'(SEQ ID NO:6214)
3'-AAAAUUUUAUUUACUUCACUCUACCGU-5'(SEQ ID NO:2619)
KRAS-2325靶:5'-TTTTAAAATAAATGAAGTGAGATGGCA-3'(SEQ ID NO:4025)
5'-UCCAUUUCUUCAUGUUAAAAGAAGU-3'(SEQ ID NO:6215)
3'-AUAGGUAAAGAAGUACAAUUUUCUUCA-5'(SEQ ID NO:2620)
KRAS-2445靶:5'-TATCCATTTCTTCATGTTAAAAGAAGT-3'(SEQ ID NO:4026)
5'-CCAUUUCUUCAUGUUAAAAGAAGUC-3'(SEQ ID NO:6216)
3'-UAGGUAAAGAAGUACAAUUUUCUUCAG-5'(SEQ ID NO:2621)
KRAS-2446靶:5'-ATCCATTTCTTCATGTTAAAAGAAGTC-3'(SEQ ID NO:4027)
5'-CUCAAACUCUUAGUUUUUUUUUUUU-3'(SEQ ID NO:6217)
3'-UAGAGUUUGAGAAUCAAAAAAAAAAAA-5'(SEQ ID NO:2622)
KRAS-2473靶:5'-ATCTCAAACTCTTAGTTTTTTTTTTTT-3'(SEQ ID NO:4028)
5'-UAGUUUUUUUUUUUUACAACUAUGU-3'(SEQ ID NO:6218)
3'-GAAUCAAAAAAAAAAAAUGUUGAUACA-5'(SEQ ID NO:2623)
KRAS-2483靶:5'-CTTAGTTTTTTTTTTTTACAACTATGT-3'(SEQ ID NO:4029)
5'-AGUUUUUUUUUUUUACAACUAUGUA-3'(SEQ ID NO:6219)
3'-AAUCAAAAAAAAAAAAUGUUGAUACAU-5'(SEQ ID NO:2624)
KRAS-2484靶:5'-TTAGTTTTTTTTTTTTACAACTATGTA-3'(SEQ ID NO:4030)
5'-GUUUUUUUUUUUUACAACUAUGUAA-3'(SEQ ID NO:6220)
3'-AUCAAAAAAAAAAAAUGUUGAUACAUU-5'(SEQ ID NO:2625)
KRAS-2485靶:5'-TAGTTTTTTTTTTTTACAACTATGTAA-3'(SEQ ID NO:4031)
5'-UUUUUUUUUUUUACAACUAUGUAAU-3'(SEQ ID NO:6221)
3'-UCAAAAAAAAAAAAUGUUGAUACAUUA-5'(SEQ ID NO:2626)
KRAS-2486靶:5'-AGTTTTTTTTTTTTACAACTATGTAAT-3'(SEQ ID NO:4032)
5'-UUUUUUUUUUUACAACUAUGUAAUU-3'(SEQ ID NO:6222)
3'-CAAAAAAAAAAAAUGUUGAUACAUUAA-5'(SEQ ID NO:2627)
KRAS-2487靶:5'-GTTTTTTTTTTTTACAACTATGTAATT-3'(SEQ ID NO:4033)
5'-UUUUUUUUUUACAACUAUGUAAUUU-3'(SEQ ID NO:6223)
3'-AAAAAAAAAAAAUGUUGAUACAUUAAA-5'(SEQ ID NO:2628)
KRAS-2488靶:5'-TTTTTTTTTTTTACAACTATGTAATTT-3'(SEQ ID NO:4034)
5'-UUUUUUUUUACAACUAUGUAAUUUA-3'(SEQ ID NO:6224)
3'-AAAAAAAAAAAUGUUGAUACAUUAAAU-5'(SEQ ID NO:2629)
KRAS-2489靶:5'-TTTTTTTTTTTACAACTATGTAATTTA-3'(SEQ ID NO:4035)
5'-UUUUUUUUACAACUAUGUAAUUUAU-3'(SEQ ID NO:6225)
3'-AAAAAAAAAAUGUUGAUACAUUAAAUA-5'(SEQ ID NO:2630)
KRAS-2490靶:5'-TTTTTTTTTTACAACTATGTAATTTAT-3'(SEQ ID NO:4036)
5'-UUUUUUUACAACUAUGUAAUUUAUA-3'(SEQ ID NO:6226)
3'-AAAAAAAAAUGUUGAUACAUUAAAUAU-5'(SEQ ID NO:2631)
KRAS-2491靶:5'-TTTTTTTTTACAACTATGTAATTTATA-3'(SEQ ID NO:4037)
5'-UUUUUUACAACUAUGUAAUUUAUAU-3'(SEQ ID NO:6227)
3'-AAAAAAAAUGUUGAUACAUUAAAUAUA-5'(SEQ ID NO:2632)
KRAS-2492靶:5'-TTTTTTTTACAACTATGTAATTTATAT-3'(SEQ ID NO:4038)
5'-UUUUUACAACUAUGUAAUUUAUAUU-3'(SEQ ID NO:6228)
3'-AAAAAAAUGUUGAUACAUUAAAUAUAA-5'(SEQ ID NO:2633)
KRAS-2493靶:5'-TTTTTTTACAACTATGTAATTTATATT-3'(SEQ ID NO:4039)
5'-AACUAUGUAAUUUAUAUUCCAUUUA-3'(SEQ ID NO:6229)
3'-UGUUGAUACAUUAAAUAUAAGGUAAAU-5'(SEQ ID NO:2634)
KRAS-2500靶:5'-ACAACTATGTAATTTATATTCCATTTA-3'(SEQ ID NO:4040)
5'-ACUAUGUAAUUUAUAUUCCAUUUAC-3'(SEQ ID NO:6230)
3'-GUUGAUACAUUAAAUAUAAGGUAAAUG-5'(SEQ ID NO:2635)
KRAS-2501靶:5'-CAACTATGTAATTTATATTCCATTTAC-3'(SEQ ID NO:4041)
5'-CUAUGUAAUUUAUAUUCCAUUUACA-3'(SEQ ID NO:6231)
3'-UUGAUACAUUAAAUAUAAGGUAAAUGU-5'(SEQ ID NO:2636)
KRAS-2502靶:5'-AACTATGTAATTTATATTCCATTTACA-3'(SEQ ID NO:4042)
5'-AAUUUAUAUUCCAUUUACAUAAGGA-3'(SEQ ID NO:6232)
3'-CAUUAAAUAUAAGGUAAAUGUAUUCCU-5'(SEQ ID NO:2637)
KRAS-2508靶:5'-GTAATTTATATTCCATTTACATAAGGA-3'(SEQ ID NO:4043)
5'-AUUUAUAUUCCAUUUACAUAAGGAU-3'(SEQ ID NO:6233)
3'-AUUAAAUAUAAGGUAAAUGUAUUCCUA-5'(SEQ ID NO:2638)
KRAS-2509靶:5'-TAATTTATATTCCATTTACATAAGGAT-3'(SEQ ID NO:4044)
5'-UUUAUAUUCCAUUUACAUAAGGAUA-3'(SEQ ID NO:6234)
3'-UUAAAUAUAAGGUAAAUGUAUUCCUAU-5'(SEQ ID NO:2639)
KRAS-2510靶:5'-AATTTATATTCCATTTACATAAGGATA-3'(SEQ ID NO:4045)
5'-UUAUAUUCCAUUUACAUAAGGAUAC-3'(SEQ ID NO:6235)
3'-UAAAUAUAAGGUAAAUGUAUUCCUAUG-5'(SEQ ID NO:2640)
KRAS-2511靶:5'-ATTTATATTCCATTTACATAAGGATAC-3'(SEQ ID NO:4046)
5'-UACAUAAGGAUACACUUAUUUGUCA-3'(SEQ ID NO:6236)
3'-AAAUGUAUUCCUAUGUGAAUAAACAGU-5'(SEQ ID NO:2641)
KRAS-2523靶:5'-TTTACATAAGGATACACTTATTTGTCA-3'(SEQ ID NO:4047)
5'-UAAGGAUACACUUAUUUGUCAAGCU-3'(SEQ ID NO:6237)
3'-GUAUUCCUAUGUGAAUAAACAGUUCGA-5'(SEQ ID NO:2642)
KRAS-2527靶:5'-CATAAGGATACACTTATTTGTCAAGCT-3'(SEQ ID NO:4048)
5'-AUCUGUAAAUUUUUAACCUAUGUUA-3'(SEQ ID NO:6238)
3'-GUUAGACAUUUAAAAAUUGGAUACAAU-5'(SEQ ID NO:2643)
KRAS-2559靶:5'-CAATCTGTAAATTTTTAACCTATGTTA-3'(SEQ ID NO:4049)
5'-UCUGUAAAUUUUUAACCUAUGUUAC-3'(SEQ ID NO:6239)
3'-UUAGACAUUUAAAAAUUGGAUACAAUG-5'(SEQ ID NO:2644)
KRAS-2560靶:5'-AATCTGTAAATTTTTAACCTATGTTAC-3'(SEQ ID NO:4050)
5'-CUGUAAAUUUUUAACCUAUGUUACA-3'(SEQ ID NO:6240)
3'-UAGACAUUUAAAAAUUGGAUACAAUGU-5'(SEQ ID NO:2645)
KRAS-2561靶:5'-ATCTGTAAATTTTTAACCTATGTTACA-3'(SEQ ID NO:4051)
5'-UGCAAGAGGUGAAGUUUAUAUUUGA-3'(SEQ ID NO:6241)
3'-ACACGUUCUCCACUUCAAAUAUAAACU-5'(SEQ ID NO:2646)
KRAS-2617靶:5'-TGTGCAAGAGGTGAAGTTTATATTTGA-3'(SEQ ID NO:4052)
5'-CAAGAGGUGAAGUUUAUAUUUGAAU-3'(SEQ ID NO:6242)
3'-ACGUUCUCCACUUCAAAUAUAAACUUA-5'(SEQ ID NO:2647)
KRAS-2619靶:5'-TGCAAGAGGTGAAGTTTATATTTGAAT-3'(SEQ ID NO:4053)
5'-AAGAGGUGAAGUUUAUAUUUGAAUA-3'(SEQ ID NO:6243)
3'-CGUUCUCCACUUCAAAUAUAAACUUAU-5'(SEQ ID NO:2648)
KRAS-2620靶:5'-GCAAGAGGTGAAGTTTATATTTGAATA-3'(SEQ ID NO:4054)
5'-GAGGUGAAGUUUAUAUUUGAAUAUC-3'(SEQ ID NO:6244)
3'-UUCUCCACUUCAAAUAUAAACUUAUAG-5'(SEQ ID NO:2649)
KRAS-2622靶:5'-AAGAGGTGAAGTTTATATTTGAATATC-3'(SEQ ID NO:4055)
5'-AGGUGAAGUUUAUAUUUGAAUAUCC-3'(SEQ ID NO:6245)
3'-UCUCCACUUCAAAUAUAAACUUAUAGG-5'(SEQ ID NO:2650)
KRAS-2623靶:5'-AGAGGTGAAGTTTATATTTGAATATCC-3'(SEQ ID NO:4056)
5'-AAGUUUAUAUUUGAAUAUCCAUUCU-3'(SEQ ID NO:6246)
3'-ACUUCAAAUAUAAACUUAUAGGUAAGA-5'(SEQ ID NO:2651)
KRAS-2628靶:5'-TGAAGTTTATATTTGAATATCCATTCT-3'(SEQ ID NO:4057)
5'-ACUUGAUGCAGUUUUAAUACUUGUA-3'(SEQ ID NO:6247)
3'-ACUGAACUACGUCAAAAUUAUGAACAU-5'(SEQ ID NO:2652)
KRAS-2716靶:5'-TGACTTGATGCAGTTTTAATACTTGTA-3'(SEQ ID NO:4058)
5'-UUGAUGCAGUUUUAAUACUUGUAAU-3'(SEQ ID NO:6248)
3'-UGAACUACGUCAAAAUUAUGAACAUUA-5'(SEQ ID NO:2653)
KRAS-2718靶:5'-ACTTGATGCAGTTTTAATACTTGTAAT-3'(SEQ ID NO:4059)
5'-GAUUUGACCUAAUCACUAAUUUUCA-3'(SEQ ID NO:6249)
3'-CCCUAAACUGGAUUAGUGAUUAAAAGU-5'(SEQ ID NO:2654)
KRAS-2869靶:5'-GGGATTTGACCTAATCACTAATTTTCA-3'(SEQ ID NO:4060)
5'-ACCUAAUCACUAAUUUUCAGGUGGU-3'(SEQ ID NO:6250)
3'-ACUGGAUUAGUGAUUAAAAGUCCACCA-5'(SEQ ID NO:2655)
KRAS-2875靶:5'-TGACCTAATCACTAATTTTCAGGTGGT-3'(SEQ ID NO:4061)
5'-CAGUAGGAUUUUUCAAACCUGGUAU-3'(SEQ ID NO:6251)
3'-CUGUCAUCCUAAAAAGUUUGGACCAUA-5'(SEQ ID NO:2656)
KRAS-2944靶:5'-GACAGTAGGATTTTTCAAACCTGGTAT-3'(SEQ ID NO:4062)
5'-AGUGGAAGGAGAAUUUAAUAAAGAU-3'(SEQ ID NO:6252)
3'-GGUCACCUUCCUCUUAAAUUAUUUCUA-5'(SEQ ID NO:2657)
KRAS-2989靶:5'-CCAGTGGAAGGAGAATTTAATAAAGAT-3'(SEQ ID NO:4063)
5'-GGAAGGAGAAUUUAAUAAAGAUAGU-3'(SEQ ID NO:6253)
3'-CACCUUCCUCUUAAAUUAUUUCUAUCA-5'(SEQ ID NO:2658)
KRAS-2992靶:5'-GTGGAAGGAGAATTTAATAAAGATAGT-3'(SEQ ID NO:4064)
5'-AAGGAGAAUUUAAUAAAGAUAGUGC-3'(SEQ ID NO:6254)
3'-CCUUCCUCUUAAAUUAUUUCUAUCACG-5'(SEQ ID NO:2659)
KRAS-2994靶:5'-GGAAGGAGAATTTAATAAAGATAGTGC-3'(SEQ ID NO:4065)
5'-AGGAGAAUUUAAUAAAGAUAGUGCU-3'(SEQ ID NO:6255)
3'-CUUCCUCUUAAAUUAUUUCUAUCACGA-5'(SEQ ID NO:2660)
KRAS-2995靶:5'-GAAGGAGAATTTAATAAAGATAGTGCT-3'(SEQ ID NO:4066)
5'-GAAUUUAAUAAAGAUAGUGCUGAAA-3'(SEQ ID NO:6256)
3'-CUCUUAAAUUAUUUCUAUCACGACUUU-5'(SEQ ID NO:2661)
KRAS-2999靶:5'-GAGAATTTAATAAAGATAGTGCTGAAA-3'(SEQ ID NO:4067)
5'-UCCUUAGGUAAUCUAUAACUAGGAC-3'(SEQ ID NO:6257)
3'-UAAGGAAUCCAUUAGAUAUUGAUCCUG-5'(SEQ ID NO:2662)
KRAS-3028靶:5'-ATTCCTTAGGTAATCTATAACTAGGAC-3'(SEQ ID NO:4068)
5'-CCUUAGGUAAUCUAUAACUAGGACU-3'(SEQ ID NO:6258)
3'-AAGGAAUCCAUUAGAUAUUGAUCCUGA-5'(SEQ ID NO:2663)
KRAS-3029靶:5'-TTCCTTAGGTAATCTATAACTAGGACT-3'(SEQ ID NO:4069)
5'-AACAGUAAUACAUUCCAUUGUUUUA-3'(SEQ ID NO:6259)
3'-CAUUGUCAUUAUGUAAGGUAACAAAAU-5'(SEQ ID NO:2664)
KRAS-3063靶:5'-GTAACAGTAATACATTCCATTGTTTTA-3'(SEQ ID NO:4070)
5'-CAGUAAUACAUUCCAUUGUUUUAGU-3'(SEQ ID NO:6260)
3'-UUGUCAUUAUGUAAGGUAACAAAAUCA-5'(SEQ ID NO:2665)
KRAS-3065靶:5'-AACAGTAATACATTCCATTGTTTTAGT-3'(SEQ ID NO:4071)
5'-AGUAAUACAUUCCAUUGUUUUAGUA-3'(SEQ ID NO:6261)
3'-UGUCAUUAUGUAAGGUAACAAAAUCAU-5'(SEQ ID NO:2666)
KRAS-3066靶:5'-ACAGTAATACATTCCATTGTTTTAGTA-3'(SEQ ID NO:4072)
5'-GUAAUACAUUCCAUUGUUUUAGUAA-3'(SEQ ID NO:6262)
3'-GUCAUUAUGUAAGGUAACAAAAUCAUU-5'(SEQ ID NO:2667)
KRAS-3067靶:5'-CAGTAATACATTCCATTGTTTTAGTAA-3'(SEQ ID NO:4073)
5'-CCAUUGUUUUAGUAACCAGAAAUCU-3'(SEQ ID NO:6263)
3'-AAGGUAACAAAAUCAUUGGUCUUUAGA-5'(SEQ ID NO:2668)
KRAS-3077靶:5'-TTCCATTGTTTTAGTAACCAGAAATCT-3'(SEQ ID NO:4074)
5'-ACCAGAAAUCUUCAUGCAAUGAAAA-3'(SEQ ID NO:6264)
3'-AUUGGUCUUUAGAAGUACGUUACUUUU-5'(SEQ ID NO:2669)
KRAS-3091靶:5'-TAACCAGAAATCTTCATGCAATGAAAA-3'(SEQ ID NO:4075)
5'-UUCAUGCAAUGAAAAAUACUUUAAU-3'(SEQ ID NO:6265)
3'-AGAAGUACGUUACUUUUUAUGAAAUUA-5'(SEQ ID NO:2670)
KRAS-3101靶:5'-TCTTCATGCAATGAAAAATACTTTAAT-3'(SEQ ID NO:4076)
5'-AAUGAAAAAUACUUUAAUUCAUGAA-3'(SEQ ID NO:6266)
3'-CGUUACUUUUUAUGAAAUUAAGUACUU-5'(SEQ ID NO:2671)
KRAS-3108靶:5'-GCAATGAAAAATACTTTAATTCATGAA-3'(SEQ ID NO:4077)
5'-UGAAAAAUACUUUAAUUCAUGAAGC-3'(SEQ ID NO:6267)
3'-UUACUUUUUAUGAAAUUAAGUACUUCG-5'(SEQ ID NO:2672)
KRAS-3110靶:5'-AATGAAAAATACTTTAATTCATGAAGC-3'(SEQ ID NO:4078)
5'-GAAAAAUACUUUAAUUCAUGAAGCU-3'(SEQ ID NO:6268)
3'-UACUUUUUAUGAAAUUAAGUACUUCGA-5'(SEQ ID NO:2673)
KRAS-3111靶:5'-ATGAAAAATACTTTAATTCATGAAGCT-3'(SEQ ID NO:4079)
5'-UUCAUGAAGCUUACUUUUUUUUUUU-3'(SEQ ID NO:6269)
3'-UUAAGUACUUCGAAUGAAAAAAAAAAA-5'(SEQ ID NO:2674)
KRAS-3125靶:5'-AATTCATGAAGCTTACTTTTTTTTTTT-3'(SEQ ID NO:4080)
5'-AUGAAGCUUACUUUUUUUUUUUGGU-3'(SEQ ID NO:6270)
3'-AGUACUUCGAAUGAAAAAAAAAAACCA-5'(SEQ ID NO:2675)
KRAS-3128靶:5'-TCATGAAGCTTACTTTTTTTTTTTGGT-3'(SEQ ID NO:4081)
5'-AGCUUACUUUUUUUUUUUGGUGUCA-3'(SEQ ID NO:6271)
3'-CUUCGAAUGAAAAAAAAAAACCACAGU-5'(SEQ ID NO:2676)
KRAS-3132靶:5'-GAAGCTTACTTTTTTTTTTTGGTGTCA-3'(SEQ ID NO:4082)
5'-UACUUUUUUUUUUUGGUGUCAGAGU-3'(SEQ ID NO:6272)
3'-GAAUGAAAAAAAAAAACCACAGUCUCA-5'(SEQ ID NO:2677)
KRAS-3136靶:5'-CTTACTTTTTTTTTTTGGTGTCAGAGT-3'(SEQ ID NO:4083)
5'-ACUUUUUUUUUUUGGUGUCAGAGUC-3'(SEQ ID NO:6273)
3'-AAUGAAAAAAAAAAACCACAGUCUCAG-5'(SEQ ID NO:2678)
KRAS-3137靶:5'-TTACTTTTTTTTTTTGGTGTCAGAGTC-3'(SEQ ID NO:4084)
5'-AACUAAUUUUUGUAUUUUUAGGAGA-3'(SEQ ID NO:6274)
3'-AGUUGAUUAAAAACAUAAAAAUCCUCU-5'(SEQ ID NO:2679)
KRAS-3295靶:5'-TCAACTAATTTTTGTATTTTTAGGAGA-3'(SEQ ID NO:4085)
5'-UAAUUUUUGUAUUUUUAGGAGAGAC-3'(SEQ ID NO:6275)
3'-UGAUUAAAAACAUAAAAAUCCUCUCUG-5'(SEQ ID NO:2680)
KRAS-3298靶:5'-ACTAATTTTTGTATTTTTAGGAGAGAC-3'(SEQ ID NO:4086)
5'-CUCAUUUAUUCAGCAAAUAUUUAUU-3'(SEQ ID NO:6276)
3'-UUGAGUAAAUAAGUCGUUUAUAAAUAA-5'(SEQ ID NO:2681)
KRAS-3411靶:5'-AACTCATTTATTCAGCAAATATTTATT-3'(SEQ ID NO:4087)
5'-CAUUUAUUCAGCAAAUAUUUAUUGA-3'(SEQ ID NO:6277)
3'-GAGUAAAUAAGUCGUUUAUAAAUAACU-5'(SEQ ID NO:2682)
KRAS-3413靶:5'-CTCATTTATTCAGCAAATATTTATTGA-3'(SEQ ID NO:4088)
5'-UUUAUUCAGCAAAUAUUUAUUGAGU-3'(SEQ ID NO:6278)
3'-GUAAAUAAGUCGUUUAUAAAUAACUCA-5'(SEQ ID NO:2683)
KRAS-3415靶:5'-CATTTATTCAGCAAATATTTATTGAGT-3'(SEQ ID NO:4089)
5'-UAUUUUAGUUUUGCAAAGAAGGGGU-3'(SEQ ID NO:6279)
3'-GCAUAAAAUCAAAACGUUUCUUCCCCA-5'(SEQ ID NO:2684)
KRAS-3587靶:5'-CGTATTTTAGTTTTGCAAAGAAGGGGT-3'(SEQ ID NO:4090)
5'-CUCUAUAAUUGUUUUGCUACGAUUC-3'(SEQ ID NO:6280)
3'-UCGAGAUAUUAACAAAACGAUGCUAAG-5'(SEQ ID NO:2685)
KRAS-3628靶:5'-AGCTCTATAATTGTTTTGCTACGATTC-3'(SEQ ID NO:4091)
5'-UACUUUAUGUAAAUCACUUCAUUGU-3'(SEQ ID NO:6281)
3'-CGAUGAAAUACAUUUAGUGAAGUAACA-5'(SEQ ID NO:2686)
KRAS-3675靶:5'-GCTACTTTATGTAAATCACTTCATTGT-3'(SEQ ID NO:4092)
5'-ACUUUAUGUAAAUCACUUCAUUGUU-3'(SEQ ID NO:6282)
3'-GAUGAAAUACAUUUAGUGAAGUAACAA-5'(SEQ ID NO:2687)
KRAS-3676靶:5'-CTACTTTATGTAAATCACTTCATTGTT-3'(SEQ ID NO:4093)
5'-CUUUAUGUAAAUCACUUCAUUGUUU-3'(SEQ ID NO:6283)
3'-AUGAAAUACAUUUAGUGAAGUAACAAA-5'(SEQ ID NO:2688)
KRAS-3677靶:5'-TACTTTATGTAAATCACTTCATTGTTT-3'(SEQ ID NO:4094)
5'-UUUAUGUAAAUCACUUCAUUGUUUU-3'(SEQ ID NO:6284)
3'-UGAAAUACAUUUAGUGAAGUAACAAAA-5'(SEQ ID NO:2689)
KRAS-3678靶:5'-ACTTTATGTAAATCACTTCATTGTTTT-3'(SEQ ID NO:4095)
5'-UUAUGUAAAUCACUUCAUUGUUUUA-3'(SEQ ID NO:6285)
3'-GAAAUACAUUUAGUGAAGUAACAAAAU-5'(SEQ ID NO:2690)
KRAS-3679靶:5'-CTTTATGTAAATCACTTCATTGTTTTA-3'(SEQ ID NO:4096)
5'-UAUGUAAAUCACUUCAUUGUUUUAA-3'(SEQ ID NO:6286)
3'-AAAUACAUUUAGUGAAGUAACAAAAUU-5'(SEQ ID NO:2691)
KRAS-3680靶:5'-TTTATGTAAATCACTTCATTGTTTTAA-3'(SEQ ID NO:4097)
5'-AUGUAAAUCACUUCAUUGUUUUAAA-3'(SEQ ID NO:6287)
3'-AAUACAUUUAGUGAAGUAACAAAAUUU-5'(SEQ ID NO:2692)
KRAS-3681靶:5'-TTATGTAAATCACTTCATTGTTTTAAA-3'(SEQ ID NO:4098)
5'-AUUGUUUUAAAGGAAUAAACUUGAU-3'(SEQ ID NO:6288)
3'-AGUAACAAAAUUUCCUUAUUUGAACUA-5'(SEQ ID NO:2693)
KRAS-3695靶:5'-TCATTGTTTTAAAGGAATAAACTTGAT-3'(SEQ ID NO:4099)
5'-UUGUUUUAAAGGAAUAAACUUGAUU-3'(SEQ ID NO:6289)
3'-GUAACAAAAUUUCCUUAUUUGAACUAA-5'(SEQ ID NO:2694)
KRAS-3696靶:5'-CATTGTTTTAAAGGAATAAACTTGATT-3'(SEQ ID NO:4100)
5'-UUUUAAAGGAAUAAACUUGAUUAUA-3'(SEQ ID NO:6290)
3'-ACAAAAUUUCCUUAUUUGAACUAAUAU-5'(SEQ ID NO:2695)
KRAS-3699靶:5'-TGTTTTAAAGGAATAAACTTGATTATA-3'(SEQ ID NO:4101)
5'-UUUAAAGGAAUAAACUUGAUUAUAU-3'(SEQ ID NO:6291)
3'-CAAAAUUUCCUUAUUUGAACUAAUAUA-5'(SEQ ID NO:2696)
KRAS-3700靶:5'-GTTTTAAAGGAATAAACTTGATTATAT-3'(SEQ ID NO:4102)
5'-UUAAAGGAAUAAACUUGAUUAUAUU-3'(SEQ ID NO:6292)
3'-AAAAUUUCCUUAUUUGAACUAAUAUAA-5'(SEQ ID NO:2697)
KRAS-3701靶:5'-TTTTAAAGGAATAAACTTGATTATATT-3'(SEQ ID NO:4103)
5'-AAAGGAAUAAACUUGAUUAUAUUGU-3'(SEQ ID NO:6293)
3'-AAUUUCCUUAUUUGAACUAAUAUAACA-5'(SEQ ID NO:2698)
KRAS-3703靶:5'-TTAAAGGAATAAACTTGATTATATTGT-3'(SEQ ID NO:4104)
5'-AAGGAAUAAACUUGAUUAUAUUGUU-3'(SEQ ID NO:6294)
3'-AUUUCCUUAUUUGAACUAAUAUAACAA-5'(SEQ ID NO:2699)
KRAS-3704靶:5'-TAAAGGAATAAACTTGATTATATTGTT-3'(SEQ ID NO:4105)
5'-AGGAAUAAACUUGAUUAUAUUGUUU-3'(SEQ ID NO:6295)
3'-UUUCCUUAUUUGAACUAAUAUAACAAA-5'(SEQ ID NO:2700)
KRAS-3705靶:5'-AAAGGAATAAACTTGATTATATTGTTT-3'(SEQ ID NO:4106)
5'-GGAAUAAACUUGAUUAUAUUGUUUU-3'(SEQ ID NO:6296)
3'-UUCCUUAUUUGAACUAAUAUAACAAAA-5'(SEQ ID NO:2701)
KRAS-3706靶:5'-AAGGAATAAACTTGATTATATTGTTTT-3'(SEQ ID NO:4107)
5'-GAAUAAACUUGAUUAUAUUGUUUUU-3'(SEQ ID NO:6297)
3'-UCCUUAUUUGAACUAAUAUAACAAAAA-5'(SEQ ID NO:2702)
KRAS-3707靶:5'-AGGAATAAACTTGATTATATTGTTTTT-3'(SEQ ID NO:4108)
5'-AACUUGAUUAUAUUGUUUUUUUAUU-3'(SEQ ID NO:6298)
3'-AUUUGAACUAAUAUAACAAAAAAAUAA-5'(SEQ ID NO:2703)
KRAS-3712靶:5'-TAAACTTGATTATATTGTTTTTTTATT-3'(SEQ ID NO:4109)
5'-ACUUGAUUAUAUUGUUUUUUUAUUU-3'(SEQ ID NO:6299)
3'-UUUGAACUAAUAUAACAAAAAAAUAAA-5'(SEQ ID NO:2704)
KRAS-3713靶:5'-AAACTTGATTATATTGTTTTTTTATTT-3'(SEQ ID NO:4110)
5'-UGAUUAUAUUGUUUUUUUAUUUGGC-3'(SEQ ID NO:6300)
3'-GAACUAAUAUAACAAAAAAAUAAACCG-5'(SEQ ID NO:2705)
KRAS-3716靶:5'-CTTGATTATATTGTTTTTTTATTTGGC-3'(SEQ ID NO:4111)
5'-AUAUUGUUUUUUUAUUUGGCAUAAC-3'(SEQ ID NO:6301)
3'-AAUAUAACAAAAAAAUAAACCGUAUUG-5'(SEQ ID NO:2706)
KRAS-3721靶:5'-TTATATTGTTTTTTTATTTGGCATAAC-3'(SEQ ID NO:4112)
5'-UAUUGUUUUUUUAUUUGGCAUAACU-3'(SEQ ID NO:6302)
3'-AUAUAACAAAAAAAUAAACCGUAUUGA-5'(SEQ ID NO:2707)
KRAS-3722靶:5'-TATATTGTTTTTTTATTTGGCATAACT-3'(SEQ ID NO:4113)
5'-GUUUUUUUAUUUGGCAUAACUGUGA-3'(SEQ ID NO:6303)
3'-AACAAAAAAAUAAACCGUAUUGACACU-5'(SEQ ID NO:2708)
KRAS-3726靶:5'-TTGTTTTTTTATTTGGCATAACTGTGA-3'(SEQ ID NO:4114)
5'-UUUUUUUAUUUGGCAUAACUGUGAU-3'(SEQ ID NO:6304)
3'-ACAAAAAAAUAAACCGUAUUGACACUA-5'(SEQ ID NO:2709)
KRAS-3727靶:5'-TGTTTTTTTATTTGGCATAACTGTGAT-3'(SEQ ID NO:4115)
5'-GCAUAACUGUGAUUCUUUUAGGACA-3'(SEQ ID NO:6305)
3'-ACCGUAUUGACACUAAGAAAAUCCUGU-5'(SEQ ID NO:2710)
KRAS-3739靶:5'-TGGCATAACTGTGATTCTTTTAGGACA-3'(SEQ ID NO:4116)
5'-ACUGUGAUUCUUUUAGGACAAUUAC-3'(SEQ ID NO:6306)
3'-AUUGACACUAAGAAAAUCCUGUUAAUG-5'(SEQ ID NO:2711)
KRAS-3744靶:5'-TAACTGTGATTCTTTTAGGACAATTAC-3'(SEQ ID NO:4117)
5'-CUGUGAUUCUUUUAGGACAAUUACU-3'(SEQ ID NO:6307)
3'-UUGACACUAAGAAAAUCCUGUUAAUGA-5'(SEQ ID NO:2712)
KRAS-3745靶:5'-AACTGTGATTCTTTTAGGACAATTACT-3'(SEQ ID NO:4118)
5'-GGUGUAUGUCAGAUAUUCAUAUUGA-3'(SEQ ID NO:6308)
3'-UUCCACAUACAGUCUAUAAGUAUAACU-5'(SEQ ID NO:2713)
KRAS-3781靶:5'-AAGGTGTATGTCAGATATTCATATTGA-3'(SEQ ID NO:4119)
5'-GUGUAUGUCAGAUAUUCAUAUUGAC-3'(SEQ ID NO:6309)
3'-UCCACAUACAGUCUAUAAGUAUAACUG-5'(SEQ ID NO:2714)
KRAS-3782靶:5'-AGGTGTATGTCAGATATTCATATTGAC-3'(SEQ ID NO:4120)
5'-CAAAUGUGUAAUAUUCCAGUUUUCU-3'(SEQ ID NO:6310)
3'-GGGUUUACACAUUAUAAGGUCAAAAGA-5'(SEQ ID NO:2715)
KRAS-3808靶:5'-CCCAAATGTGTAATATTCCAGTTTTCT-3'(SEQ ID NO:4121)
5'-CAUAAGUAAUUAAAAUAUACUUAAA-3'(SEQ ID NO:6311)
3'-ACGUAUUCAUUAAUUUUAUAUGAAUUU-5'(SEQ ID NO:2716)
KRAS-3836靶:5'-TGCATAAGTAATTAAAATATACTTAAA-3'(SEQ ID NO:4122)
5'-AUAAGUAAUUAAAAUAUACUUAAAA-3'(SEQ ID NO:6312)
3'-CGUAUUCAUUAAUUUUAUAUGAAUUUU-5'(SEQ ID NO:2717)
KRAS-3837靶:5'-GCATAAGTAATTAAAATATACTTAAAA-3'(SEQ ID NO:4123)
5'-UAAGUAAUUAAAAUAUACUUAAAAA-3'(SEQ ID NO:6313)
3'-GUAUUCAUUAAUUUUAUAUGAAUUUUU-5'(SEQ ID NO:2718)
KRAS-3838靶:5'-CATAAGTAATTAAAATATACTTAAAAA-3'(SEQ ID NO:4124)
5'-AAGUAAUUAAAAUAUACUUAAAAAU-3'(SEQ ID NO:6314)
3'-UAUUCAUUAAUUUUAUAUGAAUUUUUA-5'(SEQ ID NO:2719)
KRAS-3839靶:5'-ATAAGTAATTAAAATATACTTAAAAAT-3'(SEQ ID NO:4125)
5'-AGUAAUUAAAAUAUACUUAAAAAUU-3'(SEQ ID NO:6315)
3'-AUUCAUUAAUUUUAUAUGAAUUUUUAA-5'(SEQ ID NO:2720)
KRAS-3840靶:5'-TAAGTAATTAAAATATACTTAAAAATT-3'(SEQ ID NO:4126)
5'-GUAAUUAAAAUAUACUUAAAAAUUA-3'(SEQ ID NO:6316)
3'-UUCAUUAAUUUUAUAUGAAUUUUUAAU-5'(SEQ ID NO:2721)
KRAS-3841靶:5'-AAGTAATTAAAATATACTTAAAAATTA-3'(SEQ ID NO:4127)
5'-UAAUUAAAAUAUACUUAAAAAUUAA-3'(SEQ ID NO:6317)
3'-UCAUUAAUUUUAUAUGAAUUUUUAAUU-5'(SEQ ID NO:2722)
KRAS-3842靶:5'-AGTAATTAAAATATACTTAAAAATTAA-3'(SEQ ID NO:4128)
5'-AAUUAAAAUAUACUUAAAAAUUAAU-3'(SEQ ID NO:6318)
3'-CAUUAAUUUUAUAUGAAUUUUUAAUUA-5'(SEQ ID NO:2723)
KRAS-3843靶:5'-GTAATTAAAATATACTTAAAAATTAAT-3'(SEQ ID NO:4129)
5'-AUUAAAAUAUACUUAAAAAUUAAUA-3'(SEQ ID NO:6319)
3'-AUUAAUUUUAUAUGAAUUUUUAAUUAU-5'(SEQ ID NO:2724)
KRAS-3844靶:5'-TAATTAAAATATACTTAAAAATTAATA-3'(SEQ ID NO:4130)
5'-UAAAAUAUACUUAAAAAUUAAUAGU-3'(SEQ ID NO:6320)
3'-UAAUUUUAUAUGAAUUUUUAAUUAUCA-5'(SEQ ID NO:2725)
KRAS-3846靶:5'-ATTAAAATATACTTAAAAATTAATAGT-3'(SEQ ID NO:4131)
5'-AAAAUAUACUUAAAAAUUAAUAGUU-3'(SEQ ID NO:6321)
3'-AAUUUUAUAUGAAUUUUUAAUUAUCAA-5'(SEQ ID NO:2726)
KRAS-3847靶:5'-TTAAAATATACTTAAAAATTAATAGTT-3'(SEQ ID NO:4132)
5'-AAAUAUACUUAAAAAUUAAUAGUUU-3'(SEQ ID NO:6322)
3'-AUUUUAUAUGAAUUUUUAAUUAUCAAA-5'(SEQ ID NO:2727)
KRAS-3848靶:5'-TAAAATATACTTAAAAATTAATAGTTT-3'(SEQ ID NO:4133)
5'-AAUAUACUUAAAAAUUAAUAGUUUU-3'(SEQ ID NO:6323)
3'-UUUUAUAUGAAUUUUUAAUUAUCAAAA-5'(SEQ ID NO:2728)
KRAS-3849靶:5'-AAAATATACTTAAAAATTAATAGTTTT-3'(SEQ ID NO:4134)
5'-UACUUAAAAAUUAAUAGUUUUAUCU-3'(SEQ ID NO:6324)
3'-AUAUGAAUUUUUAAUUAUCAAAAUAGA-5'(SEQ ID NO:2729)
KRAS-3853靶:5'-TATACTTAAAAATTAATAGTTTTATCT-3'(SEQ ID NO:4135)
5'-UAAAAAUUAAUAGUUUUAUCUGGGU-3'(SEQ ID NO:6325)
3'-GAAUUUUUAAUUAUCAAAAUAGACCCA-5'(SEQ ID NO:2730)
KRAS-3857靶:5'-CTTAAAAATTAATAGTTTTATCTGGGT-3'(SEQ ID NO:4136)
5'-AAAAAUUAAUAGUUUUAUCUGGGUA-3'(SEQ ID NO:6326)
3'-AAUUUUUAAUUAUCAAAAUAGACCCAU-5'(SEQ ID NO:2731)
KRAS-3858靶:5'-TTAAAAATTAATAGTTTTATCTGGGTA-3'(SEQ ID NO:4137)
5'-AAAAUUAAUAGUUUUAUCUGGGUAC-3'(SEQ ID NO:6327)
3'-AUUUUUAAUUAUCAAAAUAGACCCAUG-5'(SEQ ID NO:2732)
KRAS-3859靶:5'-TAAAAATTAATAGTTTTATCTGGGTAC-3'(SEQ ID NO:4138)
5'-AUCUGGGUACAAAUAAACAGGUGCC-3'(SEQ ID NO:6328)
3'-AAUAGACCCAUGUUUAUUUGUCCACGG-5'(SEQ ID NO:2733)
KRAS-3874靶:5'-TTATCTGGGTACAAATAAACAGGTGCC-3'(SEQ ID NO:4139)
5'-GACAAGGAAACUUCUAUGUAAAAAU-3'(SEQ ID NO:6329)
3'-GUCUGUUCCUUUGAAGAUACAUUUUUA-5'(SEQ ID NO:2734)
KRAS-3913靶:5'-CAGACAAGGAAACTTCTATGTAAAAAT-3'(SEQ ID NO:4140)
5'-ACAAGGAAACUUCUAUGUAAAAAUC-3'(SEQ ID NO:6330)
3'-UCUGUUCCUUUGAAGAUACAUUUUUAG-5'(SEQ ID NO:2735)
KRAS-3914靶:5'-AGACAAGGAAACTTCTATGTAAAAATC-3'(SEQ ID NO:4141)
5'-CAAGGAAACUUCUAUGUAAAAAUCA-3'(SEQ ID NO:6331)
3'-CUGUUCCUUUGAAGAUACAUUUUUAGU-5'(SEQ ID NO:2736)
KRAS-3915靶:5'-GACAAGGAAACTTCTATGTAAAAATCA-3'(SEQ ID NO:4142)
5'-UUCUAUGUAAAAAUCACUAUGAUUU-3'(SEQ ID NO:6332)
3'-UGAAGAUACAUUUUUAGUGAUACUAAA-5'(SEQ ID NO:2737)
KRAS-3924靶:5'-ACTTCTATGTAAAAATCACTATGATTT-3'(SEQ ID NO:4143)
5'-UCUAUGUAAAAAUCACUAUGAUUUC-3'(SEQ ID NO:6333)
3'-GAAGAUACAUUUUUAGUGAUACUAAAG-5'(SEQ ID NO:2738)
KRAS-3925靶:5'-CTTCTATGTAAAAATCACTATGATTTC-3'(SEQ ID NO:4144)
5'-CUAUGUAAAAAUCACUAUGAUUUCU-3'(SEQ ID NO:6334)
3'-AAGAUACAUUUUUAGUGAUACUAAAGA-5'(SEQ ID NO:2739)
KRAS-3926靶:5'-TTCTATGTAAAAATCACTATGATTTCT-3'(SEQ ID NO:4145)
5'-GUAAAAAUCACUAUGAUUUCUGAAU-3'(SEQ ID NO:6335)
3'-UACAUUUUUAGUGAUACUAAAGACUUA-5'(SEQ ID NO:2740)
KRAS-3930靶:5'-ATGTAAAAATCACTATGATTTCTGAAT-3'(SEQ ID NO:4146)
5'-UAAAAAUCACUAUGAUUUCUGAAUU-3'(SEQ ID NO:6336)
3'-ACAUUUUUAGUGAUACUAAAGACUUAA-5'(SEQ ID NO:2741)
KRAS-3931靶:5'-TGTAAAAATCACTATGATTTCTGAATT-3'(SEQ ID NO:4147)
5'-CUAUGAUUUCUGAAUUGCUAUGUGA-3'(SEQ ID NO:6337)
3'-GUGAUACUAAAGACUUAACGAUACACU-5'(SEQ ID NO:2742)
KRAS-3940靶:5'-CACTATGATTTCTGAATTGCTATGTGA-3'(SEQ ID NO:4148)
5'-UAUGAUUUCUGAAUUGCUAUGUGAA-3'(SEQ ID NO:6338)
3'-UGAUACUAAAGACUUAACGAUACACUU-5'(SEQ ID NO:2743)
KRAS-3941靶:5'-ACTATGATTTCTGAATTGCTATGTGAA-3'(SEQ ID NO:4149)
5'-UAUGUGAAACUACAGAUCUUUGGAA-3'(SEQ ID NO:6339)
3'-CGAUACACUUUGAUGUCUAGAAACCUU-5'(SEQ ID NO:2744)
KRAS-3958靶:5'-GCTATGTGAAACTACAGATCTTTGGAA-3'(SEQ ID NO:4150)
5'-AUGUGAAACUACAGAUCUUUGGAAC-3'(SEQ ID NO:6340)
3'-GAUACACUUUGAUGUCUAGAAACCUUG-5'(SEQ ID NO:2745)
KRAS-3959靶:5'-CTATGTGAAACTACAGATCTTTGGAAC-3'(SEQ ID NO:4151)
5'-AGGGUGUUAAGACUUACACAGUACC-3'(SEQ ID NO:6341)
3'-CAUCCCACAAUUCUGAAUGUGUCAUGG-5'(SEQ ID NO:2746)
KRAS-3995靶:5'-GTAGGGTGTTAAGACTTACACAGTACC-3'(SEQ ID NO:4152)
5'-UUUAGGCCUCUUGAAUUUUUGAUGU-3'(SEQ ID NO:6342)
3'-AUAAAUCCGGAGAACUUAAAAACUACA-5'(SEQ ID NO:2747)
KRAS-4082靶:5'-TATTTAGGCCTCTTGAATTTTTGATGT-3'(SEQ ID NO:4153)
5'-UCUUGAAUUUUUGAUGUAGAUGGGC-3'(SEQ ID NO:6343)
3'-GGAGAACUUAAAAACUACAUCUACCCG-5'(SEQ ID NO:2748)
KRAS-4090靶:5'-CCTCTTGAATTTTTGATGTAGATGGGC-3'(SEQ ID NO:4154)
5'-CUUGAAUUUUUGAUGUAGAUGGGCA-3'(SEQ ID NO:6344)
3'-GAGAACUUAAAAACUACAUCUACCCGU-5'(SEQ ID NO:2749)
KRAS-4091靶:5'-CTCTTGAATTTTTGATGTAGATGGGCA-3'(SEQ ID NO:4155)
5'-UAGAUGGGCAUUUUUUUAAGGUAGU-3'(SEQ ID NO:6345)
3'-ACAUCUACCCGUAAAAAAAUUCCAUCA-5'(SEQ ID NO:2750)
KRAS-4106靶:5'-TGTAGATGGGCATTTTTTTAAGGTAGT-3'(SEQ ID NO:4156)
5'-GGCAUUUUUUUAAGGUAGUGGUUAA-3'(SEQ ID NO:6346)
3'-ACCCGUAAAAAAAUUCCAUCACCAAUU-5'(SEQ ID NO:2751)
KRAS-4112靶:5'-TGGGCATTTTTTTAAGGTAGTGGTTAA-3'(SEQ ID NO:4157)
5'-AGGUAGUGGUUAAUUACCUUUAUGU-3'(SEQ ID NO:6347)
3'-AUUCCAUCACCAAUUAAUGGAAAUACA-5'(SEQ ID NO:2752)
KRAS-4124靶:5'-TAAGGTAGTGGTTAATTACCTTTATGT-3'(SEQ ID NO:4158)
5'-GUAGUGGUUAAUUACCUUUAUGUGA-3'(SEQ ID NO:6348)
3'-UCCAUCACCAAUUAAUGGAAAUACACU-5'(SEQ ID NO:2753)
KRAS-4126靶:5'-AGGTAGTGGTTAATTACCTTTATGTGA-3'(SEQ ID NO:4159)
5'-UAGUGGUUAAUUACCUUUAUGUGAA-3'(SEQ ID NO:6349)
3'-CCAUCACCAAUUAAUGGAAAUACACUU-5'(SEQ ID NO:2754)
KRAS-4127靶:5'-GGTAGTGGTTAATTACCTTTATGTGAA-3'(SEQ ID NO:4160)
5'-AGUGGUUAAUUACCUUUAUGUGAAC-3'(SEQ ID NO:6350)
3'-CAUCACCAAUUAAUGGAAAUACACUUG-5'(SEQ ID NO:2755)
KRAS-4128靶:5'-GTAGTGGTTAATTACCTTTATGTGAAC-3'(SEQ ID NO:4161)
5'-GUGGUUAAUUACCUUUAUGUGAACU-3'(SEQ ID NO:6351)
3'-AUCACCAAUUAAUGGAAAUACACUUGA-5'(SEQ ID NO:2756)
KRAS-4129靶:5'-TAGTGGTTAATTACCTTTATGTGAACT-3'(SEQ ID NO:4162)
5'-ACCUUUAUGUGAACUUUGAAUGGUU-3'(SEQ ID NO:6352)
3'-AAUGGAAAUACACUUGAAACUUACCAA-5'(SEQ ID NO:2757)
KRAS-4139靶:5'-TTACCTTTATGTGAACTTTGAATGGTT-3'(SEQ ID NO:4163)
5'-UAUGUGAACUUUGAAUGGUUUAACA-3'(SEQ ID NO:6353)
3'-AAAUACACUUGAAACUUACCAAAUUGU-5'(SEQ ID NO:2758)
KRAS-4144靶:5'-TTTATGTGAACTTTGAATGGTTTAACA-3'(SEQ ID NO:4164)
5'-AACUUUGAAUGGUUUAACAAAAGAU-3'(SEQ ID NO:6354)
3'-ACUUGAAACUUACCAAAUUGUUUUCUA-5'(SEQ ID NO:2759)
KRAS-4150靶:5'-TGAACTTTGAATGGTTTAACAAAAGAT-3'(SEQ ID NO:4165)
5'-UUGAAUGGUUUAACAAAAGAUUUGU-3'(SEQ ID NO:6355)
3'-GAAACUUACCAAAUUGUUUUCUAAACA-5'(SEQ ID NO:2760)
KRAS-4154靶:5'-CTTTGAATGGTTTAACAAAAGATTTGT-3'(SEQ ID NO:4166)
5'-UGAAUGGUUUAACAAAAGAUUUGUU-3'(SEQ ID NO:6356)
3'-AAACUUACCAAAUUGUUUUCUAAACAA-5'(SEQ ID NO:2761)
KRAS-4155靶:5'-TTTGAATGGTTTAACAAAAGATTTGTT-3'(SEQ ID NO:4167)
5'-GAAUGGUUUAACAAAAGAUUUGUUU-3'(SEQ ID NO:6357)
3'-AACUUACCAAAUUGUUUUCUAAACAAA-5'(SEQ ID NO:2762)
KRAS-4156靶:5'-TTGAATGGTTTAACAAAAGATTTGTTT-3'(SEQ ID NO:4168)
5'-AAUGGUUUAACAAAAGAUUUGUUUU-3'(SEQ ID NO:6358)
3'-ACUUACCAAAUUGUUUUCUAAACAAAA-5'(SEQ ID NO:2763)
KRAS-4157靶:5'-TGAATGGTTTAACAAAAGATTTGTTTT-3'(SEQ ID NO:4169)
5'-AUGGUUUAACAAAAGAUUUGUUUUU-3'(SEQ ID NO:6359)
3'-CUUACCAAAUUGUUUUCUAAACAAAAA-5'(SEQ ID NO:2764)
KRAS-4158靶:5'-GAATGGTTTAACAAAAGATTTGTTTTT-3'(SEQ ID NO:4170)
5'-GGUUUAACAAAAGAUUUGUUUUUGU-3'(SEQ ID NO:6360)
3'-UACCAAAUUGUUUUCUAAACAAAAACA-5'(SEQ ID NO:2765)
KRAS-4160靶:5'-ATGGTTTAACAAAAGATTTGTTTTTGT-3'(SEQ ID NO:4171)
5'-GUUUAACAAAAGAUUUGUUUUUGUA-3'(SEQ ID NO:6361)
3'-ACCAAAUUGUUUUCUAAACAAAAACAU-5'(SEQ ID NO:2766)
KRAS-4161靶:5'-TGGTTTAACAAAAGATTTGTTTTTGTA-3'(SEQ ID NO:4172)
5'-AACAAAAGAUUUGUUUUUGUAGAGA-3'(SEQ ID NO:6362)
3'-AAUUGUUUUCUAAACAAAAACAUCUCU-5'(SEQ ID NO:2767)
KRAS-4165靶:5'-TTAACAAAAGATTTGTTTTTGTAGAGA-3'(SEQ ID NO:4173)
5'-ACAAAAGAUUUGUUUUUGUAGAGAU-3'(SEQ ID NO:6363)
3'-AUUGUUUUCUAAACAAAAACAUCUCUA-5'(SEQ ID NO:2768)
KRAS-4166靶:5'-TAACAAAAGATTTGTTTTTGTAGAGAT-3'(SEQ ID NO:4174)
5'-CAAAAGAUUUGUUUUUGUAGAGAUU-3'(SEQ ID NO:6364)
3'-UUGUUUUCUAAACAAAAACAUCUCUAA-5'(SEQ ID NO:2769)
KRAS-4167靶:5'-AACAAAAGATTTGTTTTTGTAGAGATT-3'(SEQ ID NO:4175)
5'-AAAGAUUUGUUUUUGUAGAGAUUUU-3'(SEQ ID NO:6365)
3'-GUUUUCUAAACAAAAACAUCUCUAAAA-5'(SEQ ID NO:2770)
KRAS-4169靶:5'-CAAAAGATTTGTTTTTGTAGAGATTTT-3'(SEQ ID NO:4176)
5'-AAGAUUUGUUUUUGUAGAGAUUUUA-3'(SEQ ID NO:6366)
3'-UUUUCUAAACAAAAACAUCUCUAAAAU-5'(SEQ ID NO:2771)
KRAS-4170靶:5'-AAAAGATTTGTTTTTGTAGAGATTTTA-3'(SEQ ID NO:4177)
5'-AGAUUUGUUUUUGUAGAGAUUUUAA-3'(SEQ ID NO:6367)
3'-UUUCUAAACAAAAACAUCUCUAAAAUU-5'(SEQ ID NO:2772)
KRAS-4171靶:5'-AAAGATTTGTTTTTGTAGAGATTTTAA-3'(SEQ ID NO:4178)
5'-GAUUUGUUUUUGUAGAGAUUUUAAA-3'(SEQ ID NO:6368)
3'-UUCUAAACAAAAACAUCUCUAAAAUUU-5'(SEQ ID NO:2773)
KRAS-4172靶:5'-AAGATTTGTTTTTGTAGAGATTTTAAA-3'(SEQ ID NO:4179)
5'-UUUUUGUAGAGAUUUUAAAGGGGGA-3'(SEQ ID NO:6369)
3'-ACAAAAACAUCUCUAAAAUUUCCCCCU-5'(SEQ ID NO:2774)
KRAS-4178靶:5'-TGTTTTTGTAGAGATTTTAAAGGGGGA-3'(SEQ ID NO:4180)
5'-AAGGGGGAGAAUUCUAGAAAUAAAU-3'(SEQ ID NO:6370)
3'-AUUUCCCCCUCUUAAGAUCUUUAUUUA-5'(SEQ ID NO:2775)
KRAS-4195靶:5'-TAAAGGGGGAGAATTCTAGAAATAAAT-3'(SEQ ID NO:4181)
5'-GGGGGAGAAUUCUAGAAAUAAAUGU-3'(SEQ ID NO:6371)
3'-UUCCCCCUCUUAAGAUCUUUAUUUACA-5'(SEQ ID NO:2776)
KRAS-4197靶:5'-AAGGGGGAGAATTCTAGAAATAAATGT-3'(SEQ ID NO:4182)
5'-GGGGAGAAUUCUAGAAAUAAAUGUU-3'(SEQ ID NO:6372)
3'-UCCCCCUCUUAAGAUCUUUAUUUACAA-5'(SEQ ID NO:2777)
KRAS-4198靶:5'-AGGGGGAGAATTCTAGAAATAAATGTT-3'(SEQ ID NO:4183)
5'-GGGAGAAUUCUAGAAAUAAAUGUUA-3'(SEQ ID NO:6373)
3'-CCCCCUCUUAAGAUCUUUAUUUACAAU-5'(SEQ ID NO:2778)
KRAS-4199靶:5'-GGGGGAGAATTCTAGAAATAAATGTTA-3'(SEQ ID NO:4184)
5'-GGAGAAUUCUAGAAAUAAAUGUUAC-3'(SEQ ID NO:6374)
3'-CCCCUCUUAAGAUCUUUAUUUACAAUG-5'(SEQ ID NO:2779)
KRAS-4200靶:5'-GGGGAGAATTCTAGAAATAAATGTTAC-3'(SEQ ID NO:4185)
5'-GAGAAUUCUAGAAAUAAAUGUUACC-3'(SEQ ID NO:6375)
3'-CCCUCUUAAGAUCUUUAUUUACAAUGG-5'(SEQ ID NO:2780)
KRAS-4201靶:5'-GGGAGAATTCTAGAAATAAATGTTACC-3'(SEQ ID NO:4186)
5'-UUCUAGAAAUAAAUGUUACCUAAUU-3'(SEQ ID NO:6376)
3'-UUAAGAUCUUUAUUUACAAUGGAUUAA-5'(SEQ ID NO:2781)
KRAS-4206靶:5'-AATTCTAGAAATAAATGTTACCTAATT-3'(SEQ ID NO:4187)
5'-UCUAGAAAUAAAUGUUACCUAAUUA-3'(SEQ ID NO:6377)
3'-UAAGAUCUUUAUUUACAAUGGAUUAAU-5'(SEQ ID NO:2782)
KRAS-4207靶:5'-ATTCTAGAAATAAATGTTACCTAATTA-3'(SEQ ID NO:4188)
5'-CUAGAAAUAAAUGUUACCUAAUUAU-3'(SEQ ID NO:6378)
3'-AAGAUCUUUAUUUACAAUGGAUUAAUA-5'(SEQ ID NO:2783)
KRAS-4208靶:5'-TTCTAGAAATAAATGTTACCTAATTAT-3'(SEQ ID NO:4189)
5'-UAGAAAUAAAUGUUACCUAAUUAUU-3'(SEQ ID NO:6379)
3'-AGAUCUUUAUUUACAAUGGAUUAAUAA-5'(SEQ ID NO:2784)
KRAS-4209靶:5'-TCTAGAAATAAATGTTACCTAATTATT-3'(SEQ ID NO:4190)
5'-AGAAAUAAAUGUUACCUAAUUAUUA-3'(SEQ ID NO:6380)
3'-GAUCUUUAUUUACAAUGGAUUAAUAAU-5'(SEQ ID NO:2785)
KRAS-4210靶:5'-CTAGAAATAAATGTTACCTAATTATTA-3'(SEQ ID NO:4191)
5'-AAAUAAAUGUUACCUAAUUAUUACA-3'(SEQ ID NO:6381)
3'-UCUUUAUUUACAAUGGAUUAAUAAUGU-5'(SEQ ID NO:2786)
KRAS-4212靶:5'-AGAAATAAATGTTACCTAATTATTACA-3'(SEQ ID NO:4192)
5'-ACCUAAUUAUUACAGCCUUAAAGAC-3'(SEQ ID NO:6382)
3'-AAUGGAUUAAUAAUGUCGGAAUUUCUG-5'(SEQ ID NO:2787)
KRAS-4223靶:5'-TTACCTAATTATTACAGCCTTAAAGAC-3'(SEQ ID NO:4193)
5'-CCUAAUUAUUACAGCCUUAAAGACA-3'(SEQ ID NO:6383)
3'-AUGGAUUAAUAAUGUCGGAAUUUCUGU-5'(SEQ ID NO:2788)
KRAS-4224靶:5'-TACCTAATTATTACAGCCTTAAAGACA-3'(SEQ ID NO:4194)
5'-CCUUAAAGACAAAAAUCCUUGUUGA-3'(SEQ ID NO:6384)
3'-UCGGAAUUUCUGUUUUUAGGAACAACU-5'(SEQ ID NO:2789)
KRAS-4238靶:5'-AGCCTTAAAGACAAAAATCCTTGTTGA-3'(SEQ ID NO:4195)
5'-UAAAGACAAAAAUCCUUGUUGAAGU-3'(SEQ ID NO:6385)
3'-GAAUUUCUGUUUUUAGGAACAACUUCA-5'(SEQ ID NO:2790)
KRAS-4241靶:5'-CTTAAAGACAAAAATCCTTGTTGAAGT-3'(SEQ ID NO:4196)
5'-UCCUUGUUGAAGUUUUUUUAAAAAA-3'(SEQ ID NO:6386)
3'-UUAGGAACAACUUCAAAAAAAUUUUUU-5'(SEQ ID NO:2791)
KRAS-4253靶:5'-AATCCTTGTTGAAGTTTTTTTAAAAAA-3'(SEQ ID NO:4197)
5'-CCUUGUUGAAGUUUUUUUAAAAAAA-3'(SEQ ID NO:6387)
3'-UAGGAACAACUUCAAAAAAAUUUUUUU-5'(SEQ ID NO:2792)
KRAS-4254靶:5'-ATCCTTGTTGAAGTTTTTTTAAAAAAA-3'(SEQ ID NO:4198)
5'-UUGUUGAAGUUUUUUUAAAAAAAGC-3'(SEQ ID NO:6388)
3'-GGAACAACUUCAAAAAAAUUUUUUUCG-5'(SEQ ID NO:2793)
KRAS-4256靶:5'-CCTTGTTGAAGTTTTTTTAAAAAAAGC-3'(SEQ ID NO:4199)
5'-UGUUGAAGUUUUUUUAAAAAAAGCU-3'(SEQ ID NO:6389)
3'-GAACAACUUCAAAAAAAUUUUUUUCGA-5'(SEQ ID NO:2794)
KRAS-4257靶:5'-CTTGTTGAAGTTTTTTTAAAAAAAGCT-3'(SEQ ID NO:4200)
5'-GAAGUUUUUUUAAAAAAAGCUAAAU-3'(SEQ ID NO:6390)
3'-AACUUCAAAAAAAUUUUUUUCGAUUUA-5'(SEQ ID NO:2795)
KRAS-4261靶:5'-TTGAAGTTTTTTTAAAAAAAGCTAAAT-3'(SEQ ID NO:4201)
5'-AAGUUUUUUUAAAAAAAGCUAAAUU-3'(SEQ ID NO:6391)
3'-ACUUCAAAAAAAUUUUUUUCGAUUUAA-5'(SEQ ID NO:2796)
KRAS-4262靶:5'-TGAAGTTTTTTTAAAAAAAGCTAAATT-3'(SEQ ID NO:4202)
5'-AGUUUUUUUAAAAAAAGCUAAAUUA-3'(SEQ ID NO:6392)
3'-CUUCAAAAAAAUUUUUUUCGAUUUAAU-5'(SEQ ID NO:2797)
KRAS-4263靶:5'-GAAGTTTTTTTAAAAAAAGCTAAATTA-3'(SEQ ID NO:4203)
5'-GUUUUUUUAAAAAAAGCUAAAUUAC-3'(SEQ ID NO:6393)
3'-UUCAAAAAAAUUUUUUUCGAUUUAAUG-5'(SEQ ID NO:2798)
KRAS-4264靶:5'-AAGTTTTTTTAAAAAAAGCTAAATTAC-3'(SEQ ID NO:4204)
5'-UUUUUUUAAAAAAAGCUAAAUUACA-3'(SEQ ID NO:6394)
3'-UCAAAAAAAUUUUUUUCGAUUUAAUGU-5'(SEQ ID NO:2799)
KRAS-4265靶:5'-AGTTTTTTTAAAAAAAGCTAAATTACA-3'(SEQ ID NO:4205)
5'-UUUAAAAAAAGCUAAAUUACAUAGA-3'(SEQ ID NO:6395)
3'-AAAAAUUUUUUUCGAUUUAAUGUAUCU-5'(SEQ ID NO:2800)
KRAS-4269靶:5'-TTTTTAAAAAAAGCTAAATTACATAGA-3'(SEQ ID NO:4206)
5'-UAAAAAAAGCUAAAUUACAUAGACU-3'(SEQ ID NO:6396)
3'-AAAUUUUUUUCGAUUUAAUGUAUCUGA-5'(SEQ ID NO:2801)
KRAS-4271靶:5'-TTTAAAAAAAGCTAAATTACATAGACT-3'(SEQ ID NO:4207)
5'-ACUUAGGCAUUAACAUGUUUGUGGA-3'(SEQ ID NO:6397)
3'-UCUGAAUCCGUAAUUGUACAAACACCU-5'(SEQ ID NO:2802)
KRAS-4293靶:5'-AGACTTAGGCATTAACATGTTTGTGGA-3'(SEQ ID NO:4208)
5'-CUUAGGCAUUAACAUGUUUGUGGAA-3'(SEQ ID NO:6398)
3'-CUGAAUCCGUAAUUGUACAAACACCUU-5'(SEQ ID NO:2803)
KRAS-4294靶:5'-GACTTAGGCATTAACATGTTTGTGGAA-3'(SEQ ID NO:4209)
5'-AGCAGACGUAUAUUGUAUCAUUUGA-3'(SEQ ID NO:6399)
3'-UAUCGUCUGCAUAUAACAUAGUAAACU-5'(SEQ ID NO:2804)
KRAS-4325靶:5'-ATAGCAGACGTATATTGTATCATTTGA-3'(SEQ ID NO:4210)
5'-GACGUAUAUUGUAUCAUUUGAGUGA-3'(SEQ ID NO:6400)
3'-GUCUGCAUAUAACAUAGUAAACUCACU-5'(SEQ ID NO:2805)
KRAS-4329靶:5'-CAGACGTATATTGTATCATTTGAGTGA-3'(SEQ ID NO:4211)
5'-CGUAUAUUGUAUCAUUUGAGUGAAU-3'(SEQ ID NO:6401)
3'-CUGCAUAUAACAUAGUAAACUCACUUA-5'(SEQ ID NO:2806)
KRAS-4331靶:5'-GACGTATATTGTATCATTTGAGTGAAT-3'(SEQ ID NO:4212)
5'-AUAUUGUAUCAUUUGAGUGAAUGUU-3'(SEQ ID NO:6402)
3'-CAUAUAACAUAGUAAACUCACUUACAA-5'(SEQ ID NO:2807)
KRAS-4334靶:5'-GTATATTGTATCATTTGAGTGAATGTT-3'(SEQ ID NO:4213)
5'-UAUUGUAUCAUUUGAGUGAAUGUUC-3'(SEQ ID NO:6403)
3'-AUAUAACAUAGUAAACUCACUUACAAG-5'(SEQ ID NO:2808)
KRAS-4335靶:5'-TATATTGTATCATTTGAGTGAATGTTC-3'(SEQ ID NO:4214)
5'-AUUGUAUCAUUUGAGUGAAUGUUCC-3'(SEQ ID NO:6404)
3'-UAUAACAUAGUAAACUCACUUACAAGG-5'(SEQ ID NO:2809)
KRAS-4336靶:5'-ATATTGTATCATTTGAGTGAATGTTCC-3'(SEQ ID NO:4215)
5'-AUAGGAAUUUAGAACCUAACUUUUA-3'(SEQ ID NO:6405)
3'-CGUAUCCUUAAAUCUUGGAUUGAAAAU-5'(SEQ ID NO:2810)
KRAS-4402靶:5'-GCATAGGAATTTAGAACCTAACTTTTA-3'(SEQ ID NO:4216)
5'-UAGGAAUUUAGAACCUAACUUUUAU-3'(SEQ ID NO:6406)
3'-GUAUCCUUAAAUCUUGGAUUGAAAAUA-5'(SEQ ID NO:2811)
KRAS-4403靶:5'-CATAGGAATTTAGAACCTAACTTTTAT-3'(SEQ ID NO:4217)
5'-AAUUUAGAACCUAACUUUUAUAGGU-3'(SEQ ID NO:6407)
3'-CCUUAAAUCUUGGAUUGAAAAUAUCCA-5'(SEQ ID NO:2812)
KRAS-4407靶:5'-GGAATTTAGAACCTAACTTTTATAGGT-3'(SEQ ID NO:4218)
5'-AUUUAGAACCUAACUUUUAUAGGUU-3'(SEQ ID NO:6408)
3'-CUUAAAUCUUGGAUUGAAAAUAUCCAA-5'(SEQ ID NO:2813)
KRAS-4408靶:5'-GAATTTAGAACCTAACTTTTATAGGTT-3'(SEQ ID NO:4219)
5'-UUUAGAACCUAACUUUUAUAGGUUA-3'(SEQ ID NO:6409)
3'-UUAAAUCUUGGAUUGAAAAUAUCCAAU-5'(SEQ ID NO:2814)
KRAS-4409靶:5'-AATTTAGAACCTAACTTTTATAGGTTA-3'(SEQ ID NO:4220)
5'-UUAGAACCUAACUUUUAUAGGUUAU-3'(SEQ ID NO:6410)
3'-UAAAUCUUGGAUUGAAAAUAUCCAAUA-5'(SEQ ID NO:2815)
KRAS-4410靶:5'-ATTTAGAACCTAACTTTTATAGGTTAT-3'(SEQ ID NO:4221)
5'-UUUUAUAGGUUAUCAAAACUGUUGU-3'(SEQ ID NO:6411)
3'-UGAAAAUAUCCAAUAGUUUUGACAACA-5'(SEQ ID NO:2816)
KRAS-4422靶:5'-ACTTTTATAGGTTATCAAAACTGTTGT-3'(SEQ ID NO:4222)
5'-UUAUAGGUUAUCAAAACUGUUGUCA-3'(SEQ ID NO:6412)
3'-AAAAUAUCCAAUAGUUUUGACAACAGU-5'(SEQ ID NO:2817)
KRAS-4424靶:5'-TTTTATAGGTTATCAAAACTGTTGTCA-3'(SEQ ID NO:4223)
5'-AAUUUUGUCCUAAUAUAUACAUAGA-3'(SEQ ID NO:6413)
3'-UGUUAAAACAGGAUUAUAUAUGUAUCU-5'(SEQ ID NO:2818)
KRAS-4458靶:5'-ACAATTTTGTCCTAATATATACATAGA-3'(SEQ ID NO:4224)
5'-AUUUUGUCCUAAUAUAUACAUAGAA-3'(SEQ ID NO:6414)
3'-GUUAAAACAGGAUUAUAUAUGUAUCUU-5'(SEQ ID NO:2819)
KRAS-4459靶:5'-CAATTTTGTCCTAATATATACATAGAA-3'(SEQ ID NO:4225)
5'-UUUUGUCCUAAUAUAUACAUAGAAA-3'(SEQ ID NO:6415)
3'-UUAAAACAGGAUUAUAUAUGUAUCUUU-5'(SEQ ID NO:2820)
KRAS-4460靶:5'-AATTTTGTCCTAATATATACATAGAAA-3'(SEQ ID NO:4226)
5'-CCUAAUAUAUACAUAGAAACUUUGU-3'(SEQ ID NO:6416)
3'-CAGGAUUAUAUAUGUAUCUUUGAAACA-5'(SEQ ID NO:2821)
KRAS-4466靶:5'-GTCCTAATATATACATAGAAACTTTGT-3'(SEQ ID NO:4227)
5'-UAUAUACAUAGAAACUUUGUGGGGC-3'(SEQ ID NO:6417)
3'-UUAUAUAUGUAUCUUUGAAACACCCCG-5'(SEQ ID NO:2822)
KRAS-4471靶:5'-AATATATACATAGAAACTTTGTGGGGC-3'(SEQ ID NO:4228)
5'-CACAAGUUCAUCUCAUUUGUAUUCC-3'(SEQ ID NO:6418)
3'-ACGUGUUCAAGUAGAGUAAACAUAAGG-5'(SEQ ID NO:2823)
KRAS-4514靶:5'-TGCACAAGTTCATCTCATTTGTATTCC-3'(SEQ ID NO:4229)
5'-CUCAUUUGUAUUCCAUUGAUUUUUU-3'(SEQ ID NO:6419)
3'-UAGAGUAAACAUAAGGUAACUAAAAAA-5'(SEQ ID NO:2824)
KRAS-4525靶:5'-ATCTCATTTGTATTCCATTGATTTTTT-3'(SEQ ID NO:4230)
5'-UCAUUUGUAUUCCAUUGAUUUUUUU-3'(SEQ ID NO:6420)
3'-AGAGUAAACAUAAGGUAACUAAAAAAA-5'(SEQ ID NO:2825)
KRAS-4526靶:5'-TCTCATTTGTATTCCATTGATTTTTTT-3'(SEQ ID NO:4231)
5'-CAUUUGUAUUCCAUUGAUUUUUUUU-3'(SEQ ID NO:6421)
3'-GAGUAAACAUAAGGUAACUAAAAAAAA-5'(SEQ ID NO:2826)
KRAS-4527靶:5'-CTCATTTGTATTCCATTGATTTTTTTT-3'(SEQ ID NO:4232)
5'-AUUUGUAUUCCAUUGAUUUUUUUUU-3'(SEQ ID NO:6422)
3'-AGUAAACAUAAGGUAACUAAAAAAAAA-5'(SEQ ID NO:2827)
KRAS-4528靶:5'-TCATTTGTATTCCATTGATTTTTTTTT-3'(SEQ ID NO:4233)
5'-UUUGUAUUCCAUUGAUUUUUUUUUU-3'(SEQ ID NO:6423)
3'-GUAAACAUAAGGUAACUAAAAAAAAAA-5'(SEQ ID NO:2828)
KRAS-4529靶:5'-CATTTGTATTCCATTGATTTTTTTTTT-3'(SEQ ID NO:4234)
5'-UUGUAUUCCAUUGAUUUUUUUUUUC-3'(SEQ ID NO:6424)
3'-UAAACAUAAGGUAACUAAAAAAAAAAG-5'(SEQ ID NO:2829)
KRAS-4530靶:5'-ATTTGTATTCCATTGATTTTTTTTTTC-3'(SEQ ID NO:4235)
5'-UGUAUUCCAUUGAUUUUUUUUUUCU-3'(SEQ ID NO:6425)
3'-AAACAUAAGGUAACUAAAAAAAAAAGA-5'(SEQ ID NO:2830)
KRAS-4531靶:5'-TTTGTATTCCATTGATTTTTTTTTTCT-3'(SEQ ID NO:4236)
5'-CAUUGAUUUUUUUUUUCUUCUAAAC-3'(SEQ ID NO:6426)
3'-AGGUAACUAAAAAAAAAAGAAGAUUUG-5'(SEQ ID NO:2831)
KRAS-4538靶:5'-TCCATTGATTTTTTTTTTCTTCTAAAC-3'(SEQ ID NO:4237)
5'-AUUGAUUUUUUUUUUCUUCUAAACA-3'(SEQ ID NO:6427)
3'-GGUAACUAAAAAAAAAAGAAGAUUUGU-5'(SEQ ID NO:2832)
KRAS-4539靶:5'-CCATTGATTTTTTTTTTCTTCTAAACA-3'(SEQ ID NO:4238)
5'-AUUUUUUUUUUCUUCUAAACAUUUU-3'(SEQ ID NO:6428)
3'-ACUAAAAAAAAAAGAAGAUUUGUAAAA-5'(SEQ ID NO:2833)
KRAS-4543靶:5'-TGATTTTTTTTTTCTTCTAAACATTTT-3'(SEQ ID NO:4239)
5'-UUUUUUUUUUCUUCUAAACAUUUUU-3'(SEQ ID NO:6429)
3'-CUAAAAAAAAAAGAAGAUUUGUAAAAA-5'(SEQ ID NO:2834)
KRAS-4544靶:5'-GATTTTTTTTTTCTTCTAAACATTTTT-3'(SEQ ID NO:4240)
5'-UUUUUUUUUCUUCUAAACAUUUUUU-3'(SEQ ID NO:6430)
3'-UAAAAAAAAAAGAAGAUUUGUAAAAAA-5'(SEQ ID NO:2835)
KRAS-4545靶:5'-ATTTTTTTTTTCTTCTAAACATTTTTT-3'(SEQ ID NO:4241)
5'-UUUUUUUUCUUCUAAACAUUUUUUC-3'(SEQ ID NO:6431)
3'-AAAAAAAAAAGAAGAUUUGUAAAAAAG-5'(SEQ ID NO:2836)
KRAS-4546靶:5'-TTTTTTTTTTCTTCTAAACATTTTTTC-3'(SEQ ID NO:4242)
5'-UUUUUUUCUUCUAAACAUUUUUUCU-3'(SEQ ID NO:6432)
3'-AAAAAAAAAGAAGAUUUGUAAAAAAGA-5'(SEQ ID NO:2837)
KRAS-4547靶:5'-TTTTTTTTTCTTCTAAACATTTTTTCT-3'(SEQ ID NO:4243)
5'-AACAUUUUUUCUUCAAACAGUAUAU-3'(SEQ ID NO:6433)
3'-AUUUGUAAAAAAGAAGUUUGUCAUAUA-5'(SEQ ID NO:2838)
KRAS-4560靶:5'-TAAACATTTTTTCTTCAAACAGTATAT-3'(SEQ ID NO:4244)
5'-ACAUUUUUUCUUCAAACAGUAUAUA-3'(SEQ ID NO:6434)
3'-UUUGUAAAAAAGAAGUUUGUCAUAUAU-5'(SEQ ID NO:2839)
KRAS-4561靶:5'-AAACATTTTTTCTTCAAACAGTATATA-3'(SEQ ID NO:4245)
5'-CAUUUUUUCUUCAAACAGUAUAUAA-3'(SEQ ID NO:6435)
3'-UUGUAAAAAAGAAGUUUGUCAUAUAUU-5'(SEQ ID NO:2840)
KRAS-4562靶:5'-AACATTTTTTCTTCAAACAGTATATAA-3'(SEQ ID NO:4246)
5'-AUUUUUUCUUCAAACAGUAUAUAAC-3'(SEQ ID NO:6436)
3'-UGUAAAAAAGAAGUUUGUCAUAUAUUG-5'(SEQ ID NO:2841)
KRAS-4563靶:5'-ACATTTTTTCTTCAAACAGTATATAAC-3'(SEQ ID NO:4247)
5'-UUUUUUCUUCAAACAGUAUAUAACU-3'(SEQ ID NO:6437)
3'-GUAAAAAAGAAGUUUGUCAUAUAUUGA-5'(SEQ ID NO:2842)
KRAS-4564靶:5'-CATTTTTTCTTCAAACAGTATATAACT-3'(SEQ ID NO:4248)
5'-UUCAAACAGUAUAUAACUUUUUUUA-3'(SEQ ID NO:6438)
3'-AGAAGUUUGUCAUAUAUUGAAAAAAAU-5'(SEQ ID NO:2843)
KRAS-4571靶:5'-TCTTCAAACAGTATATAACTTTTTTTA-3'(SEQ ID NO:4249)
5'-ACAGUAUAUAACUUUUUUUAGGGGA-3'(SEQ ID NO:6439)
3'-UUUGUCAUAUAUUGAAAAAAAUCCCCU-5'(SEQ ID NO:2844)
KRAS-4576靶:5'-AAACAGTATATAACTTTTTTTAGGGGA-3'(SEQ ID NO:4250)
5'-CAGUAUAUAACUUUUUUUAGGGGAU-3'(SEQ ID NO:6440)
3'-UUGUCAUAUAUUGAAAAAAAUCCCCUA-5'(SEQ ID NO:2845)
KRAS-4577靶:5'-AACAGTATATAACTTTTTTTAGGGGAT-3'(SEQ ID NO:4251)
5'-AGUAUAUAACUUUUUUUAGGGGAUU-3'(SEQ ID NO:6441)
3'-UGUCAUAUAUUGAAAAAAAUCCCCUAA-5'(SEQ ID NO:2846)
KRAS-4578靶:5'-ACAGTATATAACTTTTTTTAGGGGATT-3'(SEQ ID NO:4252)
5'-GUAUAUAACUUUUUUUAGGGGAUUU-3'(SEQ ID NO:6442)
3'-GUCAUAUAUUGAAAAAAAUCCCCUAAA-5'(SEQ ID NO:2847)
KRAS-4579靶:5'-CAGTATATAACTTTTTTTAGGGGATTT-3'(SEQ ID NO:4253)
5'-AACUUUUUUUAGGGGAUUUUUUUUU-3'(SEQ ID NO:6443)
3'-UAUUGAAAAAAAUCCCCUAAAAAAAAA-5'(SEQ ID NO:2848)
KRAS-4585靶:5'-ATAACTTTTTTTAGGGGATTTTTTTTT-3'(SEQ ID NO:4254)
5'-ACUUUUUUUAGGGGAUUUUUUUUUA-3'(SEQ ID NO:6444)
3'-AUUGAAAAAAAUCCCCUAAAAAAAAAU-5'(SEQ ID NO:2849)
KRAS-4586靶:5'-TAACTTTTTTTAGGGGATTTTTTTTTA-3'(SEQ ID NO:4255)
5'-GGGAUUUUUUUUUAGACAGCAAAAA-3'(SEQ ID NO:6445)
3'-UCCCCUAAAAAAAAAUCUGUCGUUUUU-5'(SEQ ID NO:2850)
KRAS-4597靶:5'-AGGGGATTTTTTTTTAGACAGCAAAAA-3'(SEQ ID NO:4256)
5'-GGAUUUUUUUUUAGACAGCAAAAAC-3'(SEQ ID NO:6446)
3'-CCCCUAAAAAAAAAUCUGUCGUUUUUG-5'(SEQ ID NO:2851)
KRAS-4598靶:5'-GGGGATTTTTTTTTAGACAGCAAAAAC-3'(SEQ ID NO:4257)
5'-GAUUUUUUUUUAGACAGCAAAAACU-3'(SEQ ID NO:6447)
3'-CCCUAAAAAAAAAUCUGUCGUUUUUGA-5'(SEQ ID NO:2852)
KRAS-4599靶:5'-GGGATTTTTTTTTAGACAGCAAAAACT-3'(SEQ ID NO:4258)
5'-UGAAGAUUUCCAUUUGUCAAAAAGU-3'(SEQ ID NO:6448)
3'-AGACUUCUAAAGGUAAACAGUUUUUCA-5'(SEQ ID NO:2853)
KRAS-4627靶:5'-TCTGAAGATTTCCATTTGTCAAAAAGT-3'(SEQ ID NO:4259)
5'-GAAGAUUUCCAUUUGUCAAAAAGUA-3'(SEQ ID NO:6449)
3'-GACUUCUAAAGGUAAACAGUUUUUCAU-5'(SEQ ID NO:2854)
KRAS-4628靶:5'-CTGAAGATTTCCATTTGTCAAAAAGTA-3'(SEQ ID NO:4260)
5'-AAGAUUUCCAUUUGUCAAAAAGUAA-3'(SEQ ID NO:6450)
3'-ACUUCUAAAGGUAAACAGUUUUUCAUU-5'(SEQ ID NO:2855)
KRAS-4629靶:5'-TGAAGATTTCCATTTGTCAAAAAGTAA-3'(SEQ ID NO:4261)
5'-AGAUUUCCAUUUGUCAAAAAGUAAU-3'(SEQ ID NO:6451)
3'-CUUCUAAAGGUAAACAGUUUUUCAUUA-5'(SEQ ID NO:2856)
KRAS-4630靶:5'-GAAGATTTCCATTTGTCAAAAAGTAAT-3'(SEQ ID NO:4262)
5'-UCCAUUUGUCAAAAAGUAAUGAUUU-3'(SEQ ID NO:6452)
3'-AAAGGUAAACAGUUUUUCAUUACUAAA-5'(SEQ ID NO:2857)
KRAS-4635靶:5'-TTTCCATTTGTCAAAAAGTAATGATTT-3'(SEQ ID NO:4263)
5'-CCAUUUGUCAAAAAGUAAUGAUUUC-3'(SEQ ID NO:6453)
3'-AAGGUAAACAGUUUUUCAUUACUAAAG-5'(SEQ ID NO:2858)
KRAS-4636靶:5'-TTCCATTTGTCAAAAAGTAATGATTTC-3'(SEQ ID NO:4264)
5'-CAUUUGUCAAAAAGUAAUGAUUUCU-3'(SEQ ID NO:6454)
3'-AGGUAAACAGUUUUUCAUUACUAAAGA-5'(SEQ ID NO:2859)
KRAS-4637靶:5'-TCCATTTGTCAAAAAGTAATGATTTCT-3'(SEQ ID NO:4265)
5'-GUCAAAAAGUAAUGAUUUCUUGAUA-3'(SEQ ID NO:6455)
3'-AACAGUUUUUCAUUACUAAAGAACUAU-5'(SEQ ID NO:2860)
KRAS-4642靶:5'-TTGTCAAAAAGTAATGATTTCTTGATA-3'(SEQ ID NO:4266)
5'-UCAAAAAGUAAUGAUUUCUUGAUAA-3'(SEQ ID NO:6456)
3'-ACAGUUUUUCAUUACUAAAGAACUAUU-5'(SEQ ID NO:2861)
KRAS-4643靶:5'-TGTCAAAAAGTAATGATTTCTTGATAA-3'(SEQ ID NO:4267)
5'-CAAAAAGUAAUGAUUUCUUGAUAAU-3'(SEQ ID NO:6457)
3'-CAGUUUUUCAUUACUAAAGAACUAUUA-5'(SEQ ID NO:2862)
KRAS-4644靶:5'-GTCAAAAAGTAATGATTTCTTGATAAT-3'(SEQ ID NO:4268)
5'-AAAAAGUAAUGAUUUCUUGAUAAUU-3'(SEQ ID NO:6458)
3'-AGUUUUUCAUUACUAAAGAACUAUUAA-5'(SEQ ID NO:2863)
KRAS-4645靶:5'-TCAAAAAGTAATGATTTCTTGATAATT-3'(SEQ ID NO:4269)
5'-AAAGUAAUGAUUUCUUGAUAAUUGU-3'(SEQ ID NO:6459)
3'-UUUUUCAUUACUAAAGAACUAUUAACA-5'(SEQ ID NO:2864)
KRAS-4647靶:5'-AAAAAGTAATGATTTCTTGATAATTGT-3'(SEQ ID NO:4270)
5'-AGUAAUGAUUUCUUGAUAAUUGUGU-3'(SEQ ID NO:6460)
3'-UUUCAUUACUAAAGAACUAUUAACACA-5'(SEQ ID NO:2865)
KRAS-4649靶:5'-AAAGTAATGATTTCTTGATAATTGTGT-3'(SEQ ID NO:4271)
5'-GUAAUGAUUUCUUGAUAAUUGUGUA-3'(SEQ ID NO:6461)
3'-UUCAUUACUAAAGAACUAUUAACACAU-5'(SEQ ID NO:2866)
KRAS-4650靶:5'-AAGTAATGATTTCTTGATAATTGTGTA-3'(SEQ ID NO:4272)
5'-AAUGAUUUCUUGAUAAUUGUGUAGU-3'(SEQ ID NO:6462)
3'-CAUUACUAAAGAACUAUUAACACAUCA-5'(SEQ ID NO:2867)
KRAS-4652靶:5'-GTAATGATTTCTTGATAATTGTGTAGT-3'(SEQ ID NO:4273)
5'-AUGAUUUCUUGAUAAUUGUGUAGUA-3'(SEQ ID NO:6463)
3'-AUUACUAAAGAACUAUUAACACAUCAU-5'(SEQ ID NO:2868)
KRAS-4653靶:5'-TAATGATTTCTTGATAATTGTGTAGTA-3'(SEQ ID NO:4274)
5'-UUCUUGAUAAUUGUGUAGUAAUGUU-3'(SEQ ID NO:6464)
3'-UAAAGAACUAUUAACACAUCAUUACAA-5'(SEQ ID NO:2869)
KRAS-4658靶:5'-ATTTCTTGATAATTGTGTAGTAATGTT-3'(SEQ ID NO:4275)
5'-UCUUGAUAAUUGUGUAGUAAUGUUU-3'(SEQ ID NO:6465)
3'-AAAGAACUAUUAACACAUCAUUACAAA-5'(SEQ ID NO:2870)
KRAS-4659靶:5'-TTTCTTGATAATTGTGTAGTAATGTTT-3'(SEQ ID NO:4276)
5'-CUUGAUAAUUGUGUAGUAAUGUUUU-3'(SEQ ID NO:6466)
3'-AAGAACUAUUAACACAUCAUUACAAAA-5'(SEQ ID NO:2871)
KRAS-4660靶:5'-TTCTTGATAATTGTGTAGTAATGTTTT-3'(SEQ ID NO:4277)
5'-UGAUAAUUGUGUAGUAAUGUUUUUU-3'(SEQ ID NO:6467)
3'-GAACUAUUAACACAUCAUUACAAAAAA-5'(SEQ ID NO:2872)
KRAS-4662靶:5'-CTTGATAATTGTGTAGTAATGTTTTTT-3'(SEQ ID NO:4278)
5'-UAAUUGUGUAGUAAUGUUUUUUAGA-3'(SEQ ID NO:6468)
3'-CUAUUAACACAUCAUUACAAAAAAUCU-5'(SEQ ID NO:2873)
KRAS-4665靶:5'-GATAATTGTGTAGTAATGTTTTTTAGA-3'(SEQ ID NO:4279)
5'-AUUGUGUAGUAAUGUUUUUUAGAAC-3'(SEQ ID NO:6469)
3'-AUUAACACAUCAUUACAAAAAAUCUUG-5'(SEQ ID NO:2874)
KRAS-4667靶:5'-TAATTGTGTAGTAATGTTTTTTAGAAC-3'(SEQ ID NO:4280)
5'-UUGUGUAGUAAUGUUUUUUAGAACC-3'(SEQ ID NO:6470)
3'-UUAACACAUCAUUACAAAAAAUCUUGG-5'(SEQ ID NO:2875)
KRAS-4668靶:5'-AATTGTGTAGTAATGTTTTTTAGAACC-3'(SEQ ID NO:4281)
5'-CCUUAAAGCUGAAUUUAUAUUUAGU-3'(SEQ ID NO:6471)
3'-AUGGAAUUUCGACUUAAAUAUAAAUCA-5'(SEQ ID NO:2876)
KRAS-4702靶:5'-TACCTTAAAGCTGAATTTATATTTAGT-3'(SEQ ID NO:4282)
5'-UUAAAGCUGAAUUUAUAUUUAGUAA-3'(SEQ ID NO:6472)
3'-GGAAUUUCGACUUAAAUAUAAAUCAUU-5'(SEQ ID NO:2877)
KRAS-4704靶:5'-CCTTAAAGCTGAATTTATATTTAGTAA-3'(SEQ ID NO:4283)
5'-AAUUUAUAUUUAGUAACUUCUGUGU-3'(SEQ ID NO:6473)
3'-ACUUAAAUAUAAAUCAUUGAAGACACA-5'(SEQ ID NO:2878)
KRAS-4713靶:5'-TGAATTTATATTTAGTAACTTCTGTGT-3'(SEQ ID NO:4284)
5'-AUUUAUAUUUAGUAACUUCUGUGUU-3'(SEQ ID NO:6474)
3'-CUUAAAUAUAAAUCAUUGAAGACACAA-5'(SEQ ID NO:2879)
KRAS-4714靶:5'-GAATTTATATTTAGTAACTTCTGTGTT-3'(SEQ ID NO:4285)
5'-UUUAUAUUUAGUAACUUCUGUGUUA-3'(SEQ ID NO:6475)
3'-UUAAAUAUAAAUCAUUGAAGACACAAU-5'(SEQ ID NO:2880)
KRAS-4715靶:5'-AATTTATATTTAGTAACTTCTGTGTTA-3'(SEQ ID NO:4286)
5'-AUUUAGUAACUUCUGUGUUAAUACU-3'(SEQ ID NO:6476)
3'-UAUAAAUCAUUGAAGACACAAUUAUGA-5'(SEQ ID NO:2881)
KRAS-4720靶:5'-ATATTTAGTAACTTCTGTGTTAATACT-3'(SEQ ID NO:4287)
5'-ACUGAAUAGCUGUCAUAAAAUGAAA-3'(SEQ ID NO:6477)
3'-UUUGACUUAUCGACAGUAUUUUACUUU-5'(SEQ ID NO:2882)
KRAS-4771靶:5'-AAACTGAATAGCTGTCATAAAATGAAA-3'(SEQ ID NO:4288)
5'-CUGAAUAGCUGUCAUAAAAUGAAAC-3'(SEQ ID NO:6478)
3'-UUGACUUAUCGACAGUAUUUUACUUUG-5'(SEQ ID NO:2883)
KRAS-4772靶:5'-AACTGAATAGCTGTCATAAAATGAAAC-3'(SEQ ID NO:4289)
5'-UAAAAUGAAACUUUCUUUCUAAAGA-3'(SEQ ID NO:6479)
3'-GUAUUUUACUUUGAAAGAAAGAUUUCU-5'(SEQ ID NO:2884)
KRAS-4786靶:5'-CATAAAATGAAACTTTCTTTCTAAAGA-3'(SEQ ID NO:4290)
5'-AAAAUGAAACUUUCUUUCUAAAGAA-3'(SEQ ID NO:6480)
3'-UAUUUUACUUUGAAAGAAAGAUUUCUU-5'(SEQ ID NO:2885)
KRAS-4787靶:5'-ATAAAATGAAACTTTCTTTCTAAAGAA-3'(SEQ ID NO:4291)
5'-AAAUGAAACUUUCUUUCUAAAGAAA-3'(SEQ ID NO:6481)
3'-AUUUUACUUUGAAAGAAAGAUUUCUUU-5'(SEQ ID NO:2886)
KRAS-4788靶:5'-TAAAATGAAACTTTCTTTCTAAAGAAA-3'(SEQ ID NO:4292)
5'-AUGAAACUUUCUUUCUAAAGAAAGA-3'(SEQ ID NO:6482)
3'-UUUACUUUGAAAGAAAGAUUUCUUUCU-5'(SEQ ID NO:2887)
KRAS-4790靶:5'-AAATGAAACTTTCTTTCTAAAGAAAGA-3'(SEQ ID NO:4293)
5'-AACUUUCUUUCUAAAGAAAGAUACU-3'(SEQ ID NO:6483)
3'-CUUUGAAAGAAAGAUUUCUUUCUAUGA-5'(SEQ ID NO:2888)
KRAS-4794靶:5'-GAAACTTTCTTTCTAAAGAAAGATACT-3'(SEQ ID NO:4294)
5'-CACAUGAGUUCUUGAAGAAUAGUCA-3'(SEQ ID NO:6484)
3'-GAGUGUACUCAAGAACUUCUUAUCAGU-5'(SEQ ID NO:2889)
KRAS-4819靶:5'-CTCACATGAGTTCTTGAAGAATAGTCA-3'(SEQ ID NO:4295)
5'-UCUUGAAGAAUAGUCAUAACUAGAU-3'(SEQ ID NO:6485)
3'-CAAGAACUUCUUAUCAGUAUUGAUCUA-5'(SEQ ID NO:2890)
KRAS-4828靶:5'-GTTCTTGAAGAATAGTCATAACTAGAT-3'(SEQ ID NO:4296)
5'-CUUGAAGAAUAGUCAUAACUAGAUU-3'(SEQ ID NO:6486)
3'-AAGAACUUCUUAUCAGUAUUGAUCUAA-5'(SEQ ID NO:2891)
KRAS-4829靶:5'-TTCTTGAAGAATAGTCATAACTAGATT-3'(SEQ ID NO:4297)
5'-UUGAAGAAUAGUCAUAACUAGAUUA-3'(SEQ ID NO:6487)
3'-AGAACUUCUUAUCAGUAUUGAUCUAAU-5'(SEQ ID NO:2892)
KRAS-4830靶:5'-TCTTGAAGAATAGTCATAACTAGATTA-3'(SEQ ID NO:4298)
5'-AAGAAUAGUCAUAACUAGAUUAAGA-3'(SEQ ID NO:6488)
3'-ACUUCUUAUCAGUAUUGAUCUAAUUCU-5'(SEQ ID NO:2893)
KRAS-4833靶:5'-TGAAGAATAGTCATAACTAGATTAAGA-3'(SEQ ID NO:4299)
5'-AGAAUAGUCAUAACUAGAUUAAGAU-3'(SEQ ID NO:6489)
3'-CUUCUUAUCAGUAUUGAUCUAAUUCUA-5'(SEQ ID NO:2894)
KRAS-4834靶:5'-GAAGAATAGTCATAACTAGATTAAGAT-3'(SEQ ID NO:4300)
5'-GAAUAGUCAUAACUAGAUUAAGAUC-3'(SEQ ID NO:6490)
3'-UUCUUAUCAGUAUUGAUCUAAUUCUAG-5'(SEQ ID NO:2895)
KRAS-4835靶:5'-AAGAATAGTCATAACTAGATTAAGATC-3'(SEQ ID NO:4301)
5'-AAUAGUCAUAACUAGAUUAAGAUCU-3'(SEQ ID NO:6491)
3'-UCUUAUCAGUAUUGAUCUAAUUCUAGA-5'(SEQ ID NO:2896)
KRAS-4836靶:5'-AGAATAGTCATAACTAGATTAAGATCT-3'(SEQ ID NO:4302)
5'-GUCAUAACUAGAUUAAGAUCUGUGU-3'(SEQ ID NO:6492)
3'-AUCAGUAUUGAUCUAAUUCUAGACACA-5'(SEQ ID NO:2897)
KRAS-4840靶:5'-TAGTCATAACTAGATTAAGATCTGTGT-3'(SEQ ID NO:4303)
5'-ACUAGAUUAAGAUCUGUGUUUUAGU-3'(SEQ ID NO:6493)
3'-AUUGAUCUAAUUCUAGACACAAAAUCA-5'(SEQ ID NO:2898)
KRAS-4846靶:5'-TAACTAGATTAAGATCTGTGTTTTAGT-3'(SEQ ID NO:4304)
5'-UAGAUUAAGAUCUGUGUUUUAGUUU-3'(SEQ ID NO:6494)
3'-UGAUCUAAUUCUAGACACAAAAUCAAA-5'(SEQ ID NO:2899)
KRAS-4848靶:5'-ACTAGATTAAGATCTGTGTTTTAGTTT-3'(SEQ ID NO:4305)
5'-AGAUUAAGAUCUGUGUUUUAGUUUA-3'(SEQ ID NO:6495)
3'-GAUCUAAUUCUAGACACAAAAUCAAAU-5'(SEQ ID NO:2900)
KRAS-4849靶:5'-CTAGATTAAGATCTGTGTTTTAGTTTA-3'(SEQ ID NO:4306)
5'-AUUAAGAUCUGUGUUUUAGUUUAAU-3'(SEQ ID NO:6496)
3'-UCUAAUUCUAGACACAAAAUCAAAUUA-5'(SEQ ID NO:2901)
KRAS-4851靶:5'-AGATTAAGATCTGTGTTTTAGTTTAAT-3'(SEQ ID NO:4307)
5'-UCUGUGUUUUAGUUUAAUAGUUUGA-3'(SEQ ID NO:6497)
3'-CUAGACACAAAAUCAAAUUAUCAAACU-5'(SEQ ID NO:2902)
KRAS-4858靶:5'-GATCTGTGTTTTAGTTTAATAGTTTGA-3'(SEQ ID NO:4308)
5'-CUGUGUUUUAGUUUAAUAGUUUGAA-3'(SEQ ID NO:6498)
3'-UAGACACAAAAUCAAAUUAUCAAACUU-5'(SEQ ID NO:2903)
KRAS-4859靶:5'-ATCTGTGTTTTAGTTTAATAGTTTGAA-3'(SEQ ID NO:4309)
5'-GUGUUUUAGUUUAAUAGUUUGAAGU-3'(SEQ ID NO:6499)
3'-GACACAAAAUCAAAUUAUCAAACUUCA-5'(SEQ ID NO:2904)
KRAS-4861靶:5'-CTGTGTTTTAGTTTAATAGTTTGAAGT-3'(SEQ ID NO:4310)
5'-GUUUUAGUUUAAUAGUUUGAAGUGC-3'(SEQ ID NO:6500)
3'-CACAAAAUCAAAUUAUCAAACUUCACG-5'(SEQ ID NO:2905)
KRAS-4863靶:5'-GTGTTTTAGTTTAATAGTTTGAAGTGC-3'(SEQ ID NO:4311)
5'-UUUUAGUUUAAUAGUUUGAAGUGCC-3'(SEQ ID NO:6501)
3'-ACAAAAUCAAAUUAUCAAACUUCACGG-5'(SEQ ID NO:2906)
KRAS-4864靶:5'-TGTTTTAGTTTAATAGTTTGAAGTGCC-3'(SEQ ID NO:4312)
5'-GUUUGGGAUAAUGAUAGGUAAUUUA-3'(SEQ ID NO:6502)
3'-GACAAACCCUAUUACUAUCCAUUAAAU-5'(SEQ ID NO:2907)
KRAS-4890靶:5'-CTGTTTGGGATAATGATAGGTAATTTA-3'(SEQ ID NO:4313)
5'-UUGGGAUAAUGAUAGGUAAUUUAGA-3'(SEQ ID NO:6503)
3'-CAAACCCUAUUACUAUCCAUUAAAUCU-5'(SEQ ID NO:2908)
KRAS-4892靶:5'-GTTTGGGATAATGATAGGTAATTTAGA-3'(SEQ ID NO:4314)
5'-GGAUAAUGAUAGGUAAUUUAGAUGA-3'(SEQ ID NO:6504)
3'-ACCCUAUUACUAUCCAUUAAAUCUACU-5'(SEQ ID NO:2909)
KRAS-4895靶:5'-TGGGATAATGATAGGTAATTTAGATGA-3'(SEQ ID NO:4315)
5'-GAUAAUGAUAGGUAAUUUAGAUGAA-3'(SEQ ID NO:6505)
3'-CCCUAUUACUAUCCAUUAAAUCUACUU-5'(SEQ ID NO:2910)
KRAS-4896靶:5'-GGGATAATGATAGGTAATTTAGATGAA-3'(SEQ ID NO:4316)
5'-AAUGAUAGGUAAUUUAGAUGAAUUU-3'(SEQ ID NO:6506)
3'-UAUUACUAUCCAUUAAAUCUACUUAAA-5'(SEQ ID NO:2911)
KRAS-4899靶:5'-ATAATGATAGGTAATTTAGATGAATTT-3'(SEQ ID NO:4317)
5'-AUGAUAGGUAAUUUAGAUGAAUUUA-3'(SEQ ID NO:6507)
3'-AUUACUAUCCAUUAAAUCUACUUAAAU-5'(SEQ ID NO:2912)
KRAS-4900靶:5'-TAATGATAGGTAATTTAGATGAATTTA-3'(SEQ ID NO:4318)
5'-AGGUAAUUUAGAUGAAUUUAGGGGA-3'(SEQ ID NO:6508)
3'-UAUCCAUUAAAUCUACUUAAAUCCCCU-5'(SEQ ID NO:2913)
KRAS-4905靶:5'-ATAGGTAATTTAGATGAATTTAGGGGA-3'(SEQ ID NO:4319)
5'-GUAAUUUAGAUGAAUUUAGGGGAAA-3'(SEQ ID NO:6509)
3'-UCCAUUAAAUCUACUUAAAUCCCCUUU-5'(SEQ ID NO:2914)
KRAS-4907靶:5'-AGGTAATTTAGATGAATTTAGGGGAAA-3'(SEQ ID NO:4320)
5'-AGAUGAAUUUAGGGGAAAAAAAAGU-3'(SEQ ID NO:6510)
3'-AAUCUACUUAAAUCCCCUUUUUUUUCA-5'(SEQ ID NO:2915)
KRAS-4914靶:5'-TTAGATGAATTTAGGGGAAAAAAAAGT-3'(SEQ ID NO:4321)
5'-GAUGAAUUUAGGGGAAAAAAAAGUU-3'(SEQ ID NO:6511)
3'-AUCUACUUAAAUCCCCUUUUUUUUCAA-5'(SEQ ID NO:2916)
KRAS-4915靶:5'-TAGATGAATTTAGGGGAAAAAAAAGTT-3'(SEQ ID NO:4322)
5'-GGGAAAAAAAAGUUAUCUGCAGAUA-3'(SEQ ID NO:6512)
3'-UCCCCUUUUUUUUCAAUAGACGUCUAU-5'(SEQ ID NO:2917)
KRAS-4926靶:5'-AGGGGAAAAAAAAGTTATCTGCAGATA-3'(SEQ ID NO:4323)
5'-GGAAAAAAAAGUUAUCUGCAGAUAU-3'(SEQ ID NO:6513)
3'-CCCCUUUUUUUUCAAUAGACGUCUAUA-5'(SEQ ID NO:2918)
KRAS-4927靶:5'-GGGGAAAAAAAAGTTATCTGCAGATAT-3'(SEQ ID NO:4324)
5'-AAAAAGUUAUCUGCAGAUAUGUUGA-3'(SEQ ID NO:6514)
3'-UUUUUUUCAAUAGACGUCUAUACAACU-5'(SEQ ID NO:2919)
KRAS-4932靶:5'-AAAAAAAGTTATCTGCAGATATGTTGA-3'(SEQ ID NO:4325)
5'-GUCUUGUGUUUUCAUGUUGAAAAUA-3'(SEQ ID NO:6515)
3'-GACAGAACACAAAAGUACAACUUUUAU-5'(SEQ ID NO:2920)
KRAS-5033靶:5'-CTGTCTTGTGTTTTCATGTTGAAAATA-3'(SEQ ID NO:4326)
5'-UCUUGUGUUUUCAUGUUGAAAAUAC-3'(SEQ ID NO:6516)
3'-ACAGAACACAAAAGUACAACUUUUAUG-5'(SEQ ID NO:2921)
KRAS-5034靶:5'-TGTCTTGTGTTTTCATGTTGAAAATAC-3'(SEQ ID NO:4327)
5'-CUUGUGUUUUCAUGUUGAAAAUACU-3'(SEQ ID NO:6517)
3'-CAGAACACAAAAGUACAACUUUUAUGA-5'(SEQ ID NO:2922)
KRAS-5035靶:5'-GTCTTGTGTTTTCATGTTGAAAATACT-3'(SEQ ID NO:4328)
5'-CAUGUUGAAAAUACUUUUGCAUUUU-3'(SEQ ID NO:6518)
3'-AAGUACAACUUUUAUGAAAACGUAAAA-5'(SEQ ID NO:2923)
KRAS-5045靶:5'-TTCATGTTGAAAATACTTTTGCATTTT-3'(SEQ ID NO:4329)
5'-AUGUUGAAAAUACUUUUGCAUUUUU-3'(SEQ ID NO:6519)
3'-AGUACAACUUUUAUGAAAACGUAAAAA-5'(SEQ ID NO:2924)
KRAS-5046靶:5'-TCATGTTGAAAATACTTTTGCATTTTT-3'(SEQ ID NO:4330)
5'-UGUUGAAAAUACUUUUGCAUUUUUC-3'(SEQ ID NO:6520)
3'-GUACAACUUUUAUGAAAACGUAAAAAG-5'(SEQ ID NO:2925)
KRAS-5047靶:5'-CATGTTGAAAATACTTTTGCATTTTTC-3'(SEQ ID NO:4331)
5'-GUUGAAAAUACUUUUGCAUUUUUCC-3'(SEQ ID NO:6521)
3'-UACAACUUUUAUGAAAACGUAAAAAGG-5'(SEQ ID NO:2926)
KRAS-5048靶:5'-ATGTTGAAAATACTTTTGCATTTTTCC-3'(SEQ ID NO:4332)
5'-CUUUUGCAUUUUUCCUUUGAGUGCC-3'(SEQ ID NO:6522)
3'-AUGAAAACGUAAAAAGGAAACUCACGG-5'(SEQ ID NO:2927)
KRAS-5058靶:5'-TACTTTTGCATTTTTCCTTTGAGTGCC-3'(SEQ ID NO:4333)
5'-UGAGUGCCAAUUUCUUACUAGUACU-3'(SEQ ID NO:6523)
3'-AAACUCACGGUUAAAGAAUGAUCAUGA-5'(SEQ ID NO:2928)
KRAS-5075靶:5'-TTTGAGTGCCAATTTCTTACTAGTACT-3'(SEQ ID NO:4334)
5'-GCCAAUUUCUUACUAGUACUAUUUC-3'(SEQ ID NO:6524)
3'-CACGGUUAAAGAAUGAUCAUGAUAAAG-5'(SEQ ID NO:2929)
KRAS-5080靶:5'-GTGCCAATTTCTTACTAGTACTATTTC-3'(SEQ ID NO:4335)
5'-CCAAUUUCUUACUAGUACUAUUUCU-3'(SEQ ID NO:6525)
3'-ACGGUUAAAGAAUGAUCAUGAUAAAGA-5'(SEQ ID NO:2930)
KRAS-5081靶:5'-TGCCAATTTCTTACTAGTACTATTTCT-3'(SEQ ID NO:4336)
5'-UACUAGUACUAUUUCUUAAUGUAAC-3'(SEQ ID NO:6526)
3'-GAAUGAUCAUGAUAAAGAAUUACAUUG-5'(SEQ ID NO:2931)
KRAS-5090靶:5'-CTTACTAGTACTATTTCTTAATGTAAC-3'(SEQ ID NO:4337)
5'-ACUAGUACUAUUUCUUAAUGUAACA-3'(SEQ ID NO:6527)
3'-AAUGAUCAUGAUAAAGAAUUACAUUGU-5'(SEQ ID NO:2932)
KRAS-5091靶:5'-TTACTAGTACTATTTCTTAATGTAACA-3'(SEQ ID NO:4338)
5'-UACUAUUUCUUAAUGUAACAUGUUU-3'(SEQ ID NO:6528)
3'-UCAUGAUAAAGAAUUACAUUGUACAAA-5'(SEQ ID NO:2933)
KRAS-5096靶:5'-AGTACTATTTCTTAATGTAACATGTTT-3'(SEQ ID NO:4339)
5'-ACUAUUUCUUAAUGUAACAUGUUUA-3'(SEQ ID NO:6529)
3'-CAUGAUAAAGAAUUACAUUGUACAAAU-5'(SEQ ID NO:2934)
KRAS-5097靶:5'-GTACTATTTCTTAATGTAACATGTTTA-3'(SEQ ID NO:4340)
5'-CUAUUUCUUAAUGUAACAUGUUUAC-3'(SEQ ID NO:6530)
3'-AUGAUAAAGAAUUACAUUGUACAAAUG-5'(SEQ ID NO:2935)
KRAS-5098靶:5'-TACTATTTCTTAATGTAACATGTTTAC-3'(SEQ ID NO:4341)
5'-UUAAUGUAACAUGUUUACCUGGAAU-3'(SEQ ID NO:6531)
3'-AGAAUUACAUUGUACAAAUGGACCUUA-5'(SEQ ID NO:2936)
KRAS-5105靶:5'-TCTTAATGTAACATGTTTACCTGGAAT-3'(SEQ ID NO:4342)
5'-CCUGGAAUGUAUUUUAACUAUUUUU-3'(SEQ ID NO:6532)
3'-AUGGACCUUACAUAAAAUUGAUAAAAA-5'(SEQ ID NO:2937)
KRAS-5122靶:5'-TACCTGGAATGTATTTTAACTATTTTT-3'(SEQ ID NO:4343)
5'-UGGAAUGUAUUUUAACUAUUUUUGU-3'(SEQ ID NO:6533)
3'-GGACCUUACAUAAAAUUGAUAAAAACA-5'(SEQ ID NO:2938)
KRAS-5124靶:5'-CCTGGAATGTATTTTAACTATTTTTGT-3'(SEQ ID NO:4344)
5'-GGAAUGUAUUUUAACUAUUUUUGUA-3'(SEQ ID NO:6534)
3'-GACCUUACAUAAAAUUGAUAAAAACAU-5'(SEQ ID NO:2939)
KRAS-5125靶:5'-CTGGAATGTATTTTAACTATTTTTGTA-3'(SEQ ID NO:4345)
5'-GAAUGUAUUUUAACUAUUUUUGUAU-3'(SEQ ID NO:6535)
3'-ACCUUACAUAAAAUUGAUAAAAACAUA-5'(SEQ ID NO:2940)
KRAS-5126靶:5'-TGGAATGTATTTTAACTATTTTTGTAT-3'(SEQ ID NO:4346)
5'-AAUGUAUUUUAACUAUUUUUGUAUA-3'(SEQ ID NO:6536)
3'-CCUUACAUAAAAUUGAUAAAAACAUAU-5'(SEQ ID NO:2941)
KRAS-5127靶:5'-GGAATGTATTTTAACTATTTTTGTATA-3'(SEQ ID NO:4347)
5'-UGUAUUUUAACUAUUUUUGUAUAGU-3'(SEQ ID NO:6537)
3'-UUACAUAAAAUUGAUAAAAACAUAUCA-5'(SEQ ID NO:2942)
KRAS-5129靶:5'-AATGTATTTTAACTATTTTTGTATAGT-3'(SEQ ID NO:4348)
5'-UAUUUUAACUAUUUUUGUAUAGUGU-3'(SEQ ID NO:6538)
3'-ACAUAAAAUUGAUAAAAACAUAUCACA-5'(SEQ ID NO:2943)
KRAS-5131靶:5'-TGTATTTTAACTATTTTTGTATAGTGT-3'(SEQ ID NO:4349)
5'-AUUUUAACUAUUUUUGUAUAGUGUA-3'(SEQ ID NO:6539)
3'-CAUAAAAUUGAUAAAAACAUAUCACAU-5'(SEQ ID NO:2944)
KRAS-5132靶:5'-GTATTTTAACTATTTTTGTATAGTGTA-3'(SEQ ID NO:4350)
5'-UUUUAACUAUUUUUGUAUAGUGUAA-3'(SEQ ID NO:6540)
3'-AUAAAAUUGAUAAAAACAUAUCACAUU-5'(SEQ ID NO:2945)
KRAS-5133靶:5'-TATTTTAACTATTTTTGTATAGTGTAA-3'(SEQ ID NO:4351)
5'-UAUUUUUGUAUAGUGUAAACUGAAA-3'(SEQ ID NO:6541)
3'-UGAUAAAAACAUAUCACAUUUGACUUU-5'(SEQ ID NO:2946)
KRAS-5140靶:5'-ACTATTTTTGTATAGTGTAAACTGAAA-3'(SEQ ID NO:4352)
5'-AUUUUUGUAUAGUGUAAACUGAAAC-3'(SEQ ID NO:6542)
3'-GAUAAAAACAUAUCACAUUUGACUUUG-5'(SEQ ID NO:2947)
KRAS-5141靶:5'-CTATTTTTGTATAGTGTAAACTGAAAC-3'(SEQ ID NO:4353)
5'-UUUUUGUAUAGUGUAAACUGAAACA-3'(SEQ ID NO:6543)
3'-AUAAAAACAUAUCACAUUUGACUUUGU-5'(SEQ ID NO:2948)
KRAS-5142靶:5'-TATTTTTGTATAGTGTAAACTGAAACA-3'(SEQ ID NO:4354)
5'-AACUGAAACAUGCACAUUUUGUACA-3'(SEQ ID NO:6544)
3'-AUUUGACUUUGUACGUGUAAAACAUGU-5'(SEQ ID NO:2949)
KRAS-5157靶:5'-TAAACTGAAACATGCACATTTTGTACA-3'(SEQ ID NO:4355)
5'-AACAUGCACAUUUUGUACAUUGUGC-3'(SEQ ID NO:6545)
3'-CUUUGUACGUGUAAAACAUGUAACACG-5'(SEQ ID NO:2950)
KRAS-5163靶:5'-GAAACATGCACATTTTGTACATTGTGC-3'(SEQ ID NO:4356)
5'-UCCAGUUGUUUUCCAUCAUUUGGUU-3'(SEQ ID NO:6546)
3'-CUAGGUCAACAAAAGGUAGUAAACCAA-5'(SEQ ID NO:2951)
KRAS-5216靶:5'-GATCCAGTTGTTTTCCATCATTTGGTT-3'(SEQ ID NO:4357)
5'-CAGUUGUUUUCCAUCAUUUGGUUGC-3'(SEQ ID NO:6547)
3'-AGGUCAACAAAAGGUAGUAAACCAACG-5'(SEQ ID NO:2952)
KRAS-5218靶:5'-TCCAGTTGTTTTCCATCATTTGGTTGC-3'(SEQ ID NO:4358)
5'-AUGUUGGUCAUAUCAAACAUUAAAA-3'(SEQ ID NO:6548)
3'-CUUACAACCAGUAUAGUUUGUAAUUUU-5'(SEQ ID NO:2953)
KRAS-5255靶:5'-GAATGTTGGTCATATCAAACATTAAAA-3'(SEQ ID NO:4359)
5'-UGUUGGUCAUAUCAAACAUUAAAAA-3'(SEQ ID NO:6549)
3'-UUACAACCAGUAUAGUUUGUAAUUUUU-5'(SEQ ID NO:2954)
KRAS-5256靶:5'-AATGTTGGTCATATCAAACATTAAAAA-3'(SEQ ID NO:4360)
5'-GUUGGUCAUAUCAAACAUUAAAAAU-3'(SEQ ID NO:6550)
3'-UACAACCAGUAUAGUUUGUAAUUUUUA-5'(SEQ ID NO:2955)
KRAS-5257靶:5'-ATGTTGGTCATATCAAACATTAAAAAT-3'(SEQ ID NO:4361)
5'-GUCAUAUCAAACAUUAAAAAUGACC-3'(SEQ ID NO:6551)
3'-ACCAGUAUAGUUUGUAAUUUUUACUGG-5'(SEQ ID NO:2956)
KRAS-5261靶:5'-TGGTCATATCAAACATTAAAAATGACC-3'(SEQ ID NO:4362)
5'-AAAAUGACCACUCUUUUAAUUGAAA-3'(SEQ ID NO:6552)
3'-AUUUUUACUGGUGAGAAAAUUAACUUU-5'(SEQ ID NO:2957)
KRAS-5277靶:5'-TAAAAATGACCACTCTTTTAATTGAAA-3'(SEQ ID NO:4363)
5'-AAAUGACCACUCUUUUAAUUGAAAU-3'(SEQ ID NO:6553)
3'-UUUUUACUGGUGAGAAAAUUAACUUUA-5'(SEQ ID NO:2958)
KRAS-5278靶:5'-AAAAATGACCACTCTTTTAATTGAAAT-3'(SEQ ID NO:4364)
5'-CUCUUUUAAUUGAAAUUAACUUUUA-3'(SEQ ID NO:6554)
3'-GUGAGAAAAUUAACUUUAAUUGAAAAU-5'(SEQ ID NO:2959)
KRAS-5287靶:5'-CACTCTTTTAATTGAAATTAACTTTTA-3'(SEQ ID NO:4365)
5'-UCUUUUAAUUGAAAUUAACUUUUAA-3'(SEQ ID NO:6555)
3'-UGAGAAAAUUAACUUUAAUUGAAAAUU-5'(SEQ ID NO:2960)
KRAS-5288靶:5'-ACTCTTTTAATTGAAATTAACTTTTAA-3'(SEQ ID NO:4366)
5'-UUUUAAUUGAAAUUAACUUUUAAAU-3'(SEQ ID NO:6556)
3'-AGAAAAUUAACUUUAAUUGAAAAUUUA-5'(SEQ ID NO:2961)
KRAS-5290靶:5'-TCTTTTAATTGAAATTAACTTTTAAAT-3'(SEQ ID NO:4367)
5'-UUAAUUGAAAUUAACUUUUAAAUGU-3'(SEQ ID NO:6557)
3'-AAAAUUAACUUUAAUUGAAAAUUUACA-5'(SEQ ID NO:2962)
KRAS-5292靶:5'-TTTTAATTGAAATTAACTTTTAAATGT-3'(SEQ ID NO:4368)
5'-UAAUUGAAAUUAACUUUUAAAUGUU-3'(SEQ ID NO:6558)
3'-AAAUUAACUUUAAUUGAAAAUUUACAA-5'(SEQ ID NO:2963)
KRAS-5293靶:5'-TTTAATTGAAATTAACTTTTAAATGTT-3'(SEQ ID NO:4369)
5'-AAUUGAAAUUAACUUUUAAAUGUUU-3'(SEQ ID NO:6559)
3'-AAUUAACUUUAAUUGAAAAUUUACAAA-5'(SEQ ID NO:2964)
KRAS-5294靶:5'-TTAATTGAAATTAACTTTTAAATGTTT-3'(SEQ ID NO:4370)
5'-AUUGAAAUUAACUUUUAAAUGUUUA-3'(SEQ ID NO:6560)
3'-AUUAACUUUAAUUGAAAAUUUACAAAU-5'(SEQ ID NO:2965)
KRAS-5295靶:5'-TAATTGAAATTAACTTTTAAATGTTTA-3'(SEQ ID NO:4371)
5'-UUGAAAUUAACUUUUAAAUGUUUAU-3'(SEQ ID NO:6561)
3'-UUAACUUUAAUUGAAAAUUUACAAAUA-5'(SEQ ID NO:2966)
KRAS-5296靶:5'-AATTGAAATTAACTTTTAAATGTTTAT-3'(SEQ ID NO:4372)
5'-UGAAAUUAACUUUUAAAUGUUUAUA-3'(SEQ ID NO:6562)
3'-UAACUUUAAUUGAAAAUUUACAAAUAU-5'(SEQ ID NO:2967)
KRAS-5297靶:5'-ATTGAAATTAACTTTTAAATGTTTATA-3'(SEQ ID NO:4373)
5'-AAUUAACUUUUAAAUGUUUAUAGGA-3'(SEQ ID NO:6563)
3'-CUUUAAUUGAAAAUUUACAAAUAUCCU-5'(SEQ ID NO:2968)
KRAS-5300靶:5'-GAAATTAACTTTTAAATGTTTATAGGA-3'(SEQ ID NO:4374)
5'-AACUUUUAAAUGUUUAUAGGAGUAU-3'(SEQ ID NO:6564)
3'-AAUUGAAAAUUUACAAAUAUCCUCAUA-5'(SEQ ID NO:2969)
KRAS-5304靶:5'-TTAACTTTTAAATGTTTATAGGAGTAT-3'(SEQ ID NO:4375)
5'-UUUAAAUGUUUAUAGGAGUAUGUGC-3'(SEQ ID NO:6565)
3'-GAAAAUUUACAAAUAUCCUCAUACACG-5'(SEQ ID NO:2970)
KRAS-5308靶:5'-CTTTTAAATGTTTATAGGAGTATGTGC-3'(SEQ ID NO:4376)
5'-UUAAAUGUUUAUAGGAGUAUGUGCU-3'(SEQ ID NO:6566)
3'-AAAAUUUACAAAUAUCCUCAUACACGA-5'(SEQ ID NO:2971)
KRAS-5309靶:5'-TTTTAAATGTTTATAGGAGTATGTGCT-3'(SEQ ID NO:4377)
5'-GCUGUGAAGUGAUCUAAAAUUUGUA-3'(SEQ ID NO:6567)
3'-CACGACACUUCACUAGAUUUUAAACAU-5'(SEQ ID NO:2972)
KRAS-5331靶:5'-GTGCTGTGAAGTGATCTAAAATTTGTA-3'(SEQ ID NO:4378)
5'-UGUGAAGUGAUCUAAAAUUUGUAAU-3'(SEQ ID NO:6568)
3'-CGACACUUCACUAGAUUUUAAACAUUA-5'(SEQ ID NO:2973)
KRAS-5333靶:5'-GCTGTGAAGTGATCTAAAATTTGTAAT-3'(SEQ ID NO:4379)
5'-GUGAAGUGAUCUAAAAUUUGUAAUA-3'(SEQ ID NO:6569)
3'-GACACUUCACUAGAUUUUAAACAUUAU-5'(SEQ ID NO:2974)
KRAS-5334靶:5'-CTGTGAAGTGATCTAAAATTTGTAATA-3'(SEQ ID NO:4380)
5'-UGAAGUGAUCUAAAAUUUGUAAUAU-3'(SEQ ID NO:6570)
3'-ACACUUCACUAGAUUUUAAACAUUAUA-5'(SEQ ID NO:2975)
KRAS-5335靶:5'-TGTGAAGTGATCTAAAATTTGTAATAT-3'(SEQ ID NO:4381)
5'-GAAGUGAUCUAAAAUUUGUAAUAUU-3'(SEQ ID NO:6571)
3'-CACUUCACUAGAUUUUAAACAUUAUAA-5'(SEQ ID NO:2976)
KRAS-5336靶:5'-GTGAAGTGATCTAAAATTTGTAATATT-3'(SEQ ID NO:4382)
5'-AAGUGAUCUAAAAUUUGUAAUAUUU-3'(SEQ ID NO:6572)
3'-ACUUCACUAGAUUUUAAACAUUAUAAA-5'(SEQ ID NO:2977)
KRAS-5337靶:5'-TGAAGTGATCTAAAATTTGTAATATTT-3'(SEQ ID NO:4383)
5'-AGUGAUCUAAAAUUUGUAAUAUUUU-3'(SEQ ID NO:6573)
3'-CUUCACUAGAUUUUAAACAUUAUAAAA-5'(SEQ ID NO:2978)
KRAS-5338靶:5'-GAAGTGATCTAAAATTTGTAATATTTT-3'(SEQ ID NO:4384)
5'-AUCUAAAAUUUGUAAUAUUUUUGUC-3'(SEQ ID NO:6574)
3'-ACUAGAUUUUAAACAUUAUAAAAACAG-5'(SEQ ID NO:2979)
KRAS-5342靶:5'-TGATCTAAAATTTGTAATATTTTTGTC-3'(SEQ ID NO:4385)
5'-UCUAAAAUUUGUAAUAUUUUUGUCA-3'(SEQ ID NO:6575)
3'-CUAGAUUUUAAACAUUAUAAAAACAGU-5'(SEQ ID NO:2980)
KRAS-5343靶:5'-GATCTAAAATTTGTAATATTTTTGTCA-3'(SEQ ID NO:4386)
5'-AAAUUUGUAAUAUUUUUGUCAUGAA-3'(SEQ ID NO:6576)
3'-AUUUUAAACAUUAUAAAAACAGUACUU-5'(SEQ ID NO:2981)
KRAS-5347靶:5'-TAAAATTTGTAATATTTTTGTCATGAA-3'(SEQ ID NO:4387)
5'-AAUUUGUAAUAUUUUUGUCAUGAAC-3'(SEQ ID NO:6577)
3'-UUUUAAACAUUAUAAAAACAGUACUUG-5'(SEQ ID NO:2982)
KRAS-5348靶:5'-AAAATTTGTAATATTTTTGTCATGAAC-3'(SEQ ID NO:4388)
5'-AUUUGUAAUAUUUUUGUCAUGAACU-3'(SEQ ID NO:6578)
3'-UUUAAACAUUAUAAAAACAGUACUUGA-5'(SEQ ID NO:2983)
KRAS-5349靶:5'-AAATTTGTAATATTTTTGTCATGAACT-3'(SEQ ID NO:4389)
5'-GUAAUAUUUUUGUCAUGAACUGUAC-3'(SEQ ID NO:6579)
3'-AACAUUAUAAAAACAGUACUUGACAUG-5'(SEQ ID NO:2984)
KRAS-5353靶:5'-TTGTAATATTTTTGTCATGAACTGTAC-3'(SEQ ID NO:4390)
5'-UAAUAUUUUUGUCAUGAACUGUACU-3'(SEQ ID NO:6580)
3'-ACAUUAUAAAAACAGUACUUGACAUGA-5'(SEQ ID NO:2985)
KRAS-5354靶:5'-TGTAATATTTTTGTCATGAACTGTACT-3'(SEQ ID NO:4391)
5'-AACUGUACUACUCCUAAUUAUUGUA-3'(SEQ ID NO:6581)
3'-ACUUGACAUGAUGAGGAUUAAUAACAU-5'(SEQ ID NO:2986)
KRAS-5370靶:5'-TGAACTGTACTACTCCTAATTATTGTA-3'(SEQ ID NO:4392)
5'-ACUGUACUACUCCUAAUUAUUGUAA-3'(SEQ ID NO:6582)
3'-CUUGACAUGAUGAGGAUUAAUAACAUU-5'(SEQ ID NO:2987)
KRAS-5371靶:5'-GAACTGTACTACTCCTAATTATTGTAA-3'(SEQ ID NO:4393)
5'-UCCUAAUUAUUGUAAUGUAAUAAAA-3'(SEQ ID NO:6583)
3'-UGAGGAUUAAUAACAUUACAUUAUUUU-5'(SEQ ID NO:2988)
KRAS-5381靶:5'-ACTCCTAATTATTGTAATGTAATAAAA-3'(SEQ ID NO:4394)
5'-CCUAAUUAUUGUAAUGUAAUAAAAA-3'(SEQ ID NO:6584)
3'-GAGGAUUAAUAACAUUACAUUAUUUUU-5'(SEQ ID NO:2989)
KRAS-5382靶:5'-CTCCTAATTATTGTAATGTAATAAAAA-3'(SEQ ID NO:4395)
5'-UAAUUAUUGUAAUGUAAUAAAAAUA-3'(SEQ ID NO:6585)
3'-GGAUUAAUAACAUUACAUUAUUUUUAU-5'(SEQ ID NO:2990)
KRAS-5384靶:5'-CCTAATTATTGTAATGTAATAAAAATA-3'(SEQ ID NO:4396)
5'-AUUAUUGUAAUGUAAUAAAAAUAGU-3'(SEQ ID NO:6586)
3'-AUUAAUAACAUUACAUUAUUUUUAUCA-5'(SEQ ID NO:2991)
KRAS-5386靶:5'-TAATTATTGTAATGTAATAAAAATAGT-3'(SEQ ID NO:4397)
5'-UUAUUGUAAUGUAAUAAAAAUAGUU-3'(SEQ ID NO:6587)
3'-UUAAUAACAUUACAUUAUUUUUAUCAA-5'(SEQ ID NO:2992)
KRAS-5387靶:5'-AATTATTGTAATGTAATAAAAATAGTT-3'(SEQ ID NO:4398)
5'-AUUGUAAUGUAAUAAAAAUAGUUAC-3'(SEQ ID NO:6588)
3'-AAUAACAUUACAUUAUUUUUAUCAAUG-5'(SEQ ID NO:2993)
KRAS-5389靶:5'-TTATTGTAATGTAATAAAAATAGTTAC-3'(SEQ ID NO:4399)
5'-UUGUAAUGUAAUAAAAAUAGUUACA-3'(SEQ ID NO:6589)
3'-AUAACAUUACAUUAUUUUUAUCAAUGU-5'(SEQ ID NO:2994)
KRAS-5390靶:5'-TATTGTAATGTAATAAAAATAGTTACA-3'(SEQ ID NO:4400)
5'-AAUGUAAUAAAAAUAGUUACAGUGA-3'(SEQ ID NO:6590)
3'-CAUUACAUUAUUUUUAUCAAUGUCACU-5'(SEQ ID NO:2995)
KRAS-5394靶:5'-GTAATGTAATAAAAATAGTTACAGTGA-3'(SEQ ID NO:4401)
5'-AUGUAAUAAAAAUAGUUACAGUGAC-3'(SEQ ID NO:6591)
3'-AUUACAUUAUUUUUAUCAAUGUCACUG-5'(SEQ ID NO:2996)
KRAS-5395靶:5'-TAATGTAATAAAAATAGTTACAGTGAC-3'(SEQ ID NO:4402)
5'-UGUAAUAAAAAUAGUUACAGUGACA-3'(SEQ ID NO:6592)
3'-UUACAUUAUUUUUAUCAAUGUCACUGU-5'(SEQ ID NO:2997)
KRAS-5396靶:5'-AATGTAATAAAAATAGTTACAGTGACA-3'(SEQ ID NO:4403)
5'-AAAUAGUUACAGUGACAAAAAAAAA-3'(SEQ ID NO:6593)
3'-UUUUUAUCAAUGUCACUGUUUUUUUUU-5'(SEQ ID NO:2998)
KRAS-5404靶:5'-AAAAATAGTTACAGTGACAAAAAAAAA-3'(SEQ ID NO:4404)
5'-AAUAGUUACAGUGACAAAAAAAAAA-3'(SEQ ID NO:6594)
3'-UUUUAUCAAUGUCACUGUUUUUUUUUU-5'(SEQ ID NO:2999)
KRAS-5405靶:5'-AAAATAGTTACAGTGACAAAAAAAAAA-3'(SEQ ID NO:4405)
5'-UAGUUACAGUGACAAAAAAAAAAAA-3'(SEQ ID NO:6595)
3'-UUAUCAAUGUCACUGUUUUUUUUUUUU-5'(SEQ ID NO:3000)
KRAS-5407靶:5'-AATAGTTACAGTGACAAAAAAAAAAAA-3'(SEQ ID NO:4406)
5'-GAGGCCUGCUGAAAAUGACUGAAUA-3'(SEQ ID NO:6596)
3'-CUCUCCGGACGACUUUUACUGACUUAU-5'(SEQ ID NO:4407)
KRAS-166靶:5'-GAGAGGCCTGCTGAAAATGACTGAATA-3'(SEQ ID NO:4893)
5'-AGGCCUGCUGAAAAUGACUGAAUAU-3'(SEQ ID NO:6597)
3'-UCUCCGGACGACUUUUACUGACUUAUA-5'(SEQ ID NO:4408)
KRAS-167靶:5'-AGAGGCCTGCTGAAAATGACTGAATAT-3'(SEQ ID NO:4894)
5'-GGCCUGCUGAAAAUGACUGAAUAUA-3'(SEQ ID NO:6598)
3'-CUCCGGACGACUUUUACUGACUUAUAU-5'(SEQ ID NO:4409)
KRAS-168靶:5'-GAGGCCTGCTGAAAATGACTGAATATA-3'(SEQ ID NO:4895)
5'-GCCUGCUGAAAAUGACUGAAUAUAA-3'(SEQ ID NO:6599)
3'-UCCGGACGACUUUUACUGACUUAUAUU-5'(SEQ ID NO:4410)
KRAS-169靶:5'-AGGCCTGCTGAAAATGACTGAATATAA-3'(SEQ ID NO:4896)
5'-GUUGGAGCUGGUGGCGUAGGCAAGA-3'(SEQ ID NO:6600)
3'-AUCAACCUCGACCACCGCAUCCGUUCU-5'(SEQ ID NO:4411)
KRAS-204靶:5'-TAGTTGGAGCTGGTGGCGTAGGCAAGA-3'(SEQ ID NO:4897)
5'-UUGGAGCUGGUGGCGUAGGCAAGAG-3'(SEQ ID NO:6601)
3'-UCAACCUCGACCACCGCAUCCGUUCUC-5'(SEQ ID NO:4412)
KRAS-205靶:5'-AGTTGGAGCTGGTGGCGTAGGCAAGAG-3'(SEQ ID NO:4898)
5'-UGGAGCUGGUGGCGUAGGCAAGAGU-3'(SEQ ID NO:6602)
3'-CAACCUCGACCACCGCAUCCGUUCUCA-5'(SEQ ID NO:4413)
KRAS-206靶:5'-GTTGGAGCTGGTGGCGTAGGCAAGAGT-3'(SEQ ID NO:4899)
5'-GGAGCUGGUGGCGUAGGCAAGAGUG-3'(SEQ ID NO:6603)
3'-AACCUCGACCACCGCAUCCGUUCUCAC-5'(SEQ ID NO:4414)
KRAS-207靶:5'-TTGGAGCTGGTGGCGTAGGCAAGAGTG-3'(SEQ ID NO:4900)
5'-GAGCUGGUGGCGUAGGCAAGAGUGC-3'(SEQ ID NO:6604)
3'-ACCUCGACCACCGCAUCCGUUCUCACG-5'(SEQ ID NO:4415)
KRAS-208靶:5'-TGGAGCTGGTGGCGTAGGCAAGAGTGC-3'(SEQ ID NO:4901)
5'-AGCUGGUGGCGUAGGCAAGAGUGCC-3'(SEQ ID NO:6605)
3'-CCUCGACCACCGCAUCCGUUCUCACGG-5'(SEQ ID NO:4416)
KRAS-209靶:5'-GGAGCTGGTGGCGTAGGCAAGAGTGCC-3'(SEQ ID NO:4902)
5'-GCUGGUGGCGUAGGCAAGAGUGCCU-3'(SEQ ID NO:6606)
3'-CUCGACCACCGCAUCCGUUCUCACGGA-5'(SEQ ID NO:4417)
KRAS-210靶:5'-GAGCTGGTGGCGTAGGCAAGAGTGCCT-3'(SEQ ID NO:4903)
5'-UACAGCUAAUUCAGAAUCAUUUUGU-3'(SEQ ID NO:6607)
3'-CUAUGUCGAUUAAGUCUUAGUAAAACA-5'(SEQ ID NO:4418)
KRAS-241靶:5'-GATACAGCTAATTCAGAATCATTTTGT-3'(SEQ ID NO:4904)
5'-UAAUUGAUGGAGAAACCUGUCUCUU-3'(SEQ ID NO:6608)
3'-UCAUUAACUACCUCUUUGGACAGAGAA-5'(SEQ ID NO:4419)
KRAS-313靶:5'-AGTAATTGATGGAGAAACCTGTCTCTT-3'(SEQ ID NO:4905)
5'-AAUUGAUGGAGAAACCUGUCUCUUG-3'(SEQ ID NO:6609)
3'-CAUUAACUACCUCUUUGGACAGAGAAC-5'(SEQ ID NO:4420)
KRAS-314靶:5'-GTAATTGATGGAGAAACCTGTCTCTTG-3'(SEQ ID NO:4906)
5'-GAUGGAGAAACCUGUCUCUUGGAUA-3'(SEQ ID NO:6610)
3'-AACUACCUCUUUGGACAGAGAACCUAU-5'(SEQ ID NO:4421)
KRAS-318靶:5'-TTGATGGAGAAACCTGTCTCTTGGATA-3'(SEQ ID NO:4907)
5'-CCUGUCUCUUGGAUAUUCUCGACAC-3'(SEQ ID NO:6611)
3'-UUGGACAGAGAACCUAUAAGAGCUGUG-5'(SEQ ID NO:4422)
KRAS-328靶:5'-AACCTGTCTCTTGGATATTCTCGACAC-3'(SEQ ID NO:4908)
5'-UGUCUCUUGGAUAUUCUCGACACAG-3'(SEQ ID NO:6612)
3'-GGACAGAGAACCUAUAAGAGCUGUGUC-5'(SEQ ID NO:4423)
KRAS-330靶:5'-CCTGTCTCTTGGATATTCTCGACACAG-3'(SEQ ID NO:4909)
5'-GUCUCUUGGAUAUUCUCGACACAGC-3'(SEQ ID NO:6613)
3'-GACAGAGAACCUAUAAGAGCUGUGUCG-5'(SEQ ID NO:4424)
KRAS-331靶:5'-CTGTCTCTTGGATATTCTCGACACAGC-3'(SEQ ID NO:4910)
5'-UCUCUUGGAUAUUCUCGACACAGCA-3'(SEQ ID NO:6614)
3'-ACAGAGAACCUAUAAGAGCUGUGUCGU-5'(SEQ ID NO:4425)
KRAS-332靶:5'-TGTCTCTTGGATATTCTCGACACAGCA-3'(SEQ ID NO:4911)
5'-CUCUUGGAUAUUCUCGACACAGCAG-3'(SEQ ID NO:6615)
3'-CAGAGAACCUAUAAGAGCUGUGUCGUC-5'(SEQ ID NO:4426)
KRAS-333靶:5'-GTCTCTTGGATATTCTCGACACAGCAG-3'(SEQ ID NO:4912)
5'-UCUUGGAUAUUCUCGACACAGCAGG-3'(SEQ ID NO:6616)
3'-AGAGAACCUAUAAGAGCUGUGUCGUCC-5'(SEQ ID NO:4427)
KRAS-334靶:5'-TCTCTTGGATATTCTCGACACAGCAGG-3'(SEQ ID NO:4913)
5'-CUUGGAUAUUCUCGACACAGCAGGU-3'(SEQ ID NO:6617)
3'-GAGAACCUAUAAGAGCUGUGUCGUCCA-5'(SEQ ID NO:4428)
KRAS-335靶:5'-CTCTTGGATATTCTCGACACAGCAGGT-3'(SEQ ID NO:4914)
5'-UUGGAUAUUCUCGACACAGCAGGUC-3'(SEQ ID NO:6618)
3'-AGAACCUAUAAGAGCUGUGUCGUCCAG-5'(SEQ ID NO:4429)
KRAS-336靶:5'-TCTTGGATATTCTCGACACAGCAGGTC-3'(SEQ ID NO:4915)
5'-CAGCAGGUCAAGAGGAGUACAGUGC-3'(SEQ ID NO:6619)
3'-GUGUCGUCCAGUUCUCCUCAUGUCACG-5'(SEQ ID NO:4430)
KRAS-352靶:5'-CACAGCAGGTCAAGAGGAGTACAGTGC-3'(SEQ ID NO:4916)
5'-AGCAGGUCAAGAGGAGUACAGUGCA-3'(SEQ ID NO:6620)
3'-UGUCGUCCAGUUCUCCUCAUGUCACGU-5'(SEQ ID NO:4431)
KRAS-353靶:5'-ACAGCAGGTCAAGAGGAGTACAGTGCA-3'(SEQ ID NO:4917)
5'-GCAGGUCAAGAGGAGUACAGUGCAA-3'(SEQ ID NO:6621)
3'-GUCGUCCAGUUCUCCUCAUGUCACGUU-5'(SEQ ID NO:4432)
KRAS-354靶:5'-CAGCAGGTCAAGAGGAGTACAGTGCAA-3'(SEQ ID NO:4918)
5'-AGGAGUACAGUGCAAUGAGGGACCA-3'(SEQ ID NO:6622)
3'-UCUCCUCAUGUCACGUUACUCCCUGGU-5'(SEQ ID NO:4433)
KRAS-364靶:5'-AGAGGAGTACAGTGCAATGAGGGACCA-3'(SEQ ID NO:4919)
5'-GGAGUACAGUGCAAUGAGGGACCAG-3'(SEQ ID NO:6623)
3'-CUCCUCAUGUCACGUUACUCCCUGGUC-5'(SEQ ID NO:4434)
KRAS-365靶:5'-GAGGAGTACAGTGCAATGAGGGACCAG-3'(SEQ ID NO:4920)
5'-GAGUACAGUGCAAUGAGGGACCAGU-3'(SEQ ID NO:6624)
3'-UCCUCAUGUCACGUUACUCCCUGGUCA-5'(SEQ ID NO:4435)
KRAS-366靶:5'-AGGAGTACAGTGCAATGAGGGACCAGT-3'(SEQ ID NO:4921)
5'-AGUACAGUGCAAUGAGGGACCAGUA-3'(SEQ ID NO:6625)
3'-CCUCAUGUCACGUUACUCCCUGGUCAU-5'(SEQ ID NO:4436)
KRAS-367靶:5'-GGAGTACAGTGCAATGAGGGACCAGTA-3'(SEQ ID NO:4922)
5'-GUACAGUGCAAUGAGGGACCAGUAC-3'(SEQ ID NO:6626)
3'-CUCAUGUCACGUUACUCCCUGGUCAUG-5'(SEQ ID NO:4437)
KRAS-368靶:5'-GAGTACAGTGCAATGAGGGACCAGTAC-3'(SEQ ID NO:4923)
5'-UACAGUGCAAUGAGGGACCAGUACA-3'(SEQ ID NO:6627)
3'-UCAUGUCACGUUACUCCCUGGUCAUGU-5'(SEQ ID NO:4438)
KRAS-369靶:5'-AGTACAGTGCAATGAGGGACCAGTACA-3'(SEQ ID NO:4924)
5'-ACAGUGCAAUGAGGGACCAGUACAU-3'(SEQ ID NO:6628)
3'-CAUGUCACGUUACUCCCUGGUCAUGUA-5'(SEQ ID NO:4439)
KRAS-370靶:5'-GTACAGTGCAATGAGGGACCAGTACAT-3'(SEQ ID NO:4925)
5'-CAGUGCAAUGAGGGACCAGUACAUG-3'(SEQ ID NO:6629)
3'-AUGUCACGUUACUCCCUGGUCAUGUAC-5'(SEQ ID NO:4440)
KRAS-371靶:5'-TACAGTGCAATGAGGGACCAGTACATG-3'(SEQ ID NO:4926)
5'-AGUGCAAUGAGGGACCAGUACAUGA-3'(SEQ ID NO:6630)
3'-UGUCACGUUACUCCCUGGUCAUGUACU-5'(SEQ ID NO:4441)
KRAS-372靶:5'-ACAGTGCAATGAGGGACCAGTACATGA-3'(SEQ ID NO:4927)
5'-GUAUUUGCCAUAAAUAAUACUAAAU-3'(SEQ ID NO:6631)
3'-CACAUAAACGGUAUUUAUUAUGAUUUA-5'(SEQ ID NO:4442)
KRAS-420靶:5'-GTGTATTTGCCATAAATAATACTAAAT-3'(SEQ ID NO:4928)
5'-UAUUUGCCAUAAAUAAUACUAAAUC-3'(SEQ ID NO:6632)
3'-ACAUAAACGGUAUUUAUUAUGAUUUAG-5'(SEQ ID NO:4443)
KRAS-421靶:5'-TGTATTTGCCATAAATAATACTAAATC-3'(SEQ ID NO:4929)
5'-AUUUGCCAUAAAUAAUACUAAAUCA-3'(SEQ ID NO:6633)
3'-CAUAAACGGUAUUUAUUAUGAUUUAGU-5'(SEQ ID NO:4444)
KRAS-422靶:5'-GTATTTGCCATAAATAATACTAAATCA-3'(SEQ ID NO:4930)
5'-UUUGCCAUAAAUAAUACUAAAUCAU-3'(SEQ ID NO:6634)
3'-AUAAACGGUAUUUAUUAUGAUUUAGUA-5'(SEQ ID NO:4445)
KRAS-423靶:5'-TATTTGCCATAAATAATACTAAATCAT-3'(SEQ ID NO:4931)
5'-UUGCCAUAAAUAAUACUAAAUCAUU-3'(SEQ ID NO:6635)
3'-UAAACGGUAUUUAUUAUGAUUUAGUAA-5'(SEQ ID NO:4446)
KRAS-424靶:5'-ATTTGCCATAAATAATACTAAATCATT-3'(SEQ ID NO:4932)
5'-UGCCAUAAAUAAUACUAAAUCAUUU-3'(SEQ ID NO:6636)
3'-AAACGGUAUUUAUUAUGAUUUAGUAAA-5'(SEQ ID NO:4447)
KRAS-425靶:5'-TTTGCCATAAATAATACTAAATCATTT-3'(SEQ ID NO:4933)
5'-GCCAUAAAUAAUACUAAAUCAUUUG-3'(SEQ ID NO:6637)
3'-AACGGUAUUUAUUAUGAUUUAGUAAAC-5'(SEQ ID NO:4448)
KRAS-426靶:5'-TTGCCATAAATAATACTAAATCATTTG-3'(SEQ ID NO:4934)
5'-AUACUAAAUCAUUUGAAGAUAUUCA-3'(SEQ ID NO:6638)
3'-AUUAUGAUUUAGUAAACUUCUAUAAGU-5'(SEQ ID NO:4449)
KRAS-436靶:5'-TAATACTAAATCATTTGAAGATATTCA-3'(SEQ ID NO:4935)
5'-UACUAAAUCAUUUGAAGAUAUUCAC-3'(SEQ ID NO:6639)
3'-UUAUGAUUUAGUAAACUUCUAUAAGUG-5'(SEQ ID NO:4450)
KRAS-437靶:5'-AATACTAAATCATTTGAAGATATTCAC-3'(SEQ ID NO:4936)
5'-ACUAAAUCAUUUGAAGAUAUUCACC-3'(SEQ ID NO:6640)
3'-UAUGAUUUAGUAAACUUCUAUAAGUGG-5'(SEQ ID NO:4451)
KRAS-438靶:5'-ATACTAAATCATTTGAAGATATTCACC-3'(SEQ ID NO:4937)
5'-CUAAAUCAUUUGAAGAUAUUCACCA-3'(SEQ ID NO:6641)
3'-AUGAUUUAGUAAACUUCUAUAAGUGGU-5'(SEQ ID NO:4452)
KRAS-439靶:5'-TACTAAATCATTTGAAGATATTCACCA-3'(SEQ ID NO:4938)
5'-UAAAUCAUUUGAAGAUAUUCACCAU-3'(SEQ ID NO:6642)
3'-UGAUUUAGUAAACUUCUAUAAGUGGUA-5'(SEQ ID NO:4453)
KRAS-440靶:5'-ACTAAATCATTTGAAGATATTCACCAT-3'(SEQ ID NO:4939)
5'-AAAUCAUUUGAAGAUAUUCACCAUU-3'(SEQ ID NO:6643)
3'-GAUUUAGUAAACUUCUAUAAGUGGUAA-5'(SEQ ID NO:4454)
KRAS-441靶:5'-CTAAATCATTTGAAGATATTCACCATT-3'(SEQ ID NO:4940)
5'-AAUCAUUUGAAGAUAUUCACCAUUA-3'(SEQ ID NO:6644)
3'-AUUUAGUAAACUUCUAUAAGUGGUAAU-5'(SEQ ID NO:4455)
KRAS-442靶:5'-TAAATCATTTGAAGATATTCACCATTA-3'(SEQ ID NO:4941)
5'-AUCAUUUGAAGAUAUUCACCAUUAU-3'(SEQ ID NO:6645)
3'-UUUAGUAAACUUCUAUAAGUGGUAAUA-5'(SEQ ID NO:4456)
KRAS-443靶:5'-AAATCATTTGAAGATATTCACCATTAT-3'(SEQ ID NO:4942)
5'-UCAUUUGAAGAUAUUCACCAUUAUA-3'(SEQ ID NO:6646)
3'-UUAGUAAACUUCUAUAAGUGGUAAUAU-5'(SEQ ID NO:4457)
KRAS-444靶:5'-AATCATTTGAAGATATTCACCATTATA-3'(SEQ ID NO:4943)
5'-AUAUUCACCAUUAUAGAGAACAAAU-3'(SEQ ID NO:6647)
3'-UCUAUAAGUGGUAAUAUCUCUUGUUUA-5'(SEQ ID NO:4458)
KRAS-454靶:5'-AGATATTCACCATTATAGAGAACAAAT-3'(SEQ ID NO:4944)
5'-UAUUCACCAUUAUAGAGAACAAAUU-3'(SEQ ID NO:6648)
3'-CUAUAAGUGGUAAUAUCUCUUGUUUAA-5'(SEQ ID NO:4459)
KRAS-455靶:5'-GATATTCACCATTATAGAGAACAAATT-3'(SEQ ID NO:4945)
5'-AUUCACCAUUAUAGAGAACAAAUUA-3'(SEQ ID NO:6649)
3'-UAUAAGUGGUAAUAUCUCUUGUUUAAU-5'(SEQ ID NO:4460)
KRAS-456靶:5'-ATATTCACCATTATAGAGAACAAATTA-3'(SEQ ID NO:4946)
5'-UUCACCAUUAUAGAGAACAAAUUAA-3'(SEQ ID NO:6650)
3'-AUAAGUGGUAAUAUCUCUUGUUUAAUU-5'(SEQ ID NO:4461)
KRAS-457靶:5'-TATTCACCATTATAGAGAACAAATTAA-3'(SEQ ID NO:4947)
5'-UCACCAUUAUAGAGAACAAAUUAAA-3'(SEQ ID NO:6651)
3'-UAAGUGGUAAUAUCUCUUGUUUAAUUU-5'(SEQ ID NO:4462)
KRAS-458靶:5'-ATTCACCATTATAGAGAACAAATTAAA-3'(SEQ ID NO:4948)
5'-CACCAUUAUAGAGAACAAAUUAAAA-3'(SEQ ID NO:6652)
3'-AAGUGGUAAUAUCUCUUGUUUAAUUUU-5'(SEQ ID NO:4463)
KRAS-459靶:5'-TTCACCATTATAGAGAACAAATTAAAA-3'(SEQ ID NO:4949)
5'-ACCAUUAUAGAGAACAAAUUAAAAG-3'(SEQ ID NO:6653)
3'-AGUGGUAAUAUCUCUUGUUUAAUUUUC-5'(SEQ ID NO:4464)
KRAS-460靶:5'-TCACCATTATAGAGAACAAATTAAAAG-3'(SEQ ID NO:4950)
5'-CCAUUAUAGAGAACAAAUUAAAAGA-3'(SEQ ID NO:6654)
3'-GUGGUAAUAUCUCUUGUUUAAUUUUCU-5'(SEQ ID NO:4465)
KRAS-461靶:5'-CACCATTATAGAGAACAAATTAAAAGA-3'(SEQ ID NO:4951)
5'-CAUUAUAGAGAACAAAUUAAAAGAG-3'(SEQ ID NO:6655)
3'-UGGUAAUAUCUCUUGUUUAAUUUUCUC-5'(SEQ ID NO:4466)
KRAS-462靶:5'-ACCATTATAGAGAACAAATTAAAAGAG-3'(SEQ ID NO:4952)
5'-CUAUGGUCCUAGUAGGAAAUAAAUG-3'(SEQ ID NO:6656)
3'-UGGAUACCAGGAUCAUCCUUUAUUUAC-5'(SEQ ID NO:4467)
KRAS-508靶:5'-ACCTATGGTCCTAGTAGGAAATAAATG-3'(SEQ ID NO:4953)
5'-UGUGAUUUGCCUUCUAGAACAGUAG-3'(SEQ ID NO:6657)
3'-UUACACUAAACGGAAGAUCUUGUCAUC-5'(SEQ ID NO:4468)
KRAS-531靶:5'-AATGTGATTTGCCTTCTAGAACAGTAG-3'(SEQ ID NO:4954)
5'-GUGAUUUGCCUUCUAGAACAGUAGA-3'(SEQ ID NO:6658)
3'-UACACUAAACGGAAGAUCUUGUCAUCU-5'(SEQ ID NO:4469)
KRAS-532靶:5'-ATGTGATTTGCCTTCTAGAACAGTAGA-3'(SEQ ID NO:4955)
5'-GAUUUGCCUUCUAGAACAGUAGACA-3'(SEQ ID NO:6659)
3'-CACUAAACGGAAGAUCUUGUCAUCUGU-5'(SEQ ID NO:4470)
KRAS-534靶:5'-GTGATTTGCCTTCTAGAACAGTAGACA-3'(SEQ ID NO:4956)
5'-GUUAUGGAAUUCCUUUUAUUGAAAC-3'(SEQ ID NO:6660)
3'-UUCAAUACCUUAAGGAAAAUAACUUUG-5'(SEQ ID NO:4471)
KRAS-586靶:5'-AAGTTATGGAATTCCTTTTATTGAAAC-3'(SEQ ID NO:4957)
5'-UUAUGGAAUUCCUUUUAUUGAAACA-3'(SEQ ID NO:6661)
3'-UCAAUACCUUAAGGAAAAUAACUUUGU-5'(SEQ ID NO:4472)
KRAS-587靶:5'-AGTTATGGAATTCCTTTTATTGAAACA-3'(SEQ ID NO:4958)
5'-UAUGGAAUUCCUUUUAUUGAAACAU-3'(SEQ ID NO:6662)
3'-CAAUACCUUAAGGAAAAUAACUUUGUA-5'(SEQ ID NO:4473)
KRAS-588靶:5'-GTTATGGAATTCCTTTTATTGAAACAT-3'(SEQ ID NO:4959)
5'-GAUGCCUUCUAUACAUUAGUUCGAG-3'(SEQ ID NO:6663)
3'-UACUACGGAAGAUAUGUAAUCAAGCUC-5'(SEQ ID NO:4474)
KRAS-763靶:5'-ATGATGCCTTCTATACATTAGTTCGAG-3'(SEQ ID NO:4960)
5'-AUGCCUUCUAUACAUUAGUUCGAGA-3'(SEQ ID NO:6664)
3'-ACUACGGAAGAUAUGUAAUCAAGCUCU-5'(SEQ ID NO:4475)
KRAS-764靶:5'-TGATGCCTTCTATACATTAGTTCGAGA-3'(SEQ ID NO:4961)
5'-CGAGAAAUUCGAAAACAUAAAGAAA-3'(SEQ ID NO:6665)
3'-AAGCUCUUUAAGCUUUUGUAUUUCUUU-5'(SEQ ID NO:4476)
KRAS-784靶:5'-TTCGAGAAATTCGAAAACATAAAGAAA-3'(SEQ ID NO:4962)
5'-GAAAACAUAAAGAAAAGAUGAGCAA-3'(SEQ ID NO:6666)
3'-AGCUUUUGUAUUUCUUUUCUACUCGUU-5'(SEQ ID NO:4477)
KRAS-794靶:5'-TCGAAAACATAAAGAAAAGATGAGCAA-3'(SEQ ID NO:4963)
5'-AAAACAUAAAGAAAAGAUGAGCAAA-3'(SEQ ID NO:6667)
3'-GCUUUUGUAUUUCUUUUCUACUCGUUU-5'(SEQ ID NO:4478)
KRAS-795靶:5'-CGAAAACATAAAGAAAAGATGAGCAAA-3'(SEQ ID NO:4964)
5'-AAACAUAAAGAAAAGAUGAGCAAAG-3'(SEQ ID NO:6668)
3'-CUUUUGUAUUUCUUUUCUACUCGUUUC-5'(SEQ ID NO:4479)
KRAS-796靶:5'-GAAAACATAAAGAAAAGATGAGCAAAG-3'(SEQ ID NO:4965)
5'-AACAUAAAGAAAAGAUGAGCAAAGA-3'(SEQ ID NO:6669)
3'-UUUUGUAUUUCUUUUCUACUCGUUUCU-5'(SEQ ID NO:4480)
KRAS-797靶:5'-AAAACATAAAGAAAAGATGAGCAAAGA-3'(SEQ ID NO:4966)
5'-ACAUAAAGAAAAGAUGAGCAAAGAU-3'(SEQ ID NO:6670)
3'-UUUGUAUUUCUUUUCUACUCGUUUCUA-5'(SEQ ID NO:4481)
KRAS-798靶:5'-AAACATAAAGAAAAGATGAGCAAAGAT-3'(SEQ ID NO:4967)
5'-CAUAAAGAAAAGAUGAGCAAAGAUG-3'(SEQ ID NO:6671)
3'-UUGUAUUUCUUUUCUACUCGUUUCUAC-5'(SEQ ID NO:4482)
KRAS-799靶:5'-AACATAAAGAAAAGATGAGCAAAGATG-3'(SEQ ID NO:4968)
5'-AUAAAGAAAAGAUGAGCAAAGAUGG-3'(SEQ ID NO:6672)
3'-UGUAUUUCUUUUCUACUCGUUUCUACC-5'(SEQ ID NO:4483)
KRAS-800靶:5'-ACATAAAGAAAAGATGAGCAAAGATGG-3'(SEQ ID NO:4969)
5'-UAAAGAAAAGAUGAGCAAAGAUGGU-3'(SEQ ID NO:6673)
3'-GUAUUUCUUUUCUACUCGUUUCUACCA-5'(SEQ ID NO:4484)
KRAS-801靶:5'-CATAAAGAAAAGATGAGCAAAGATGGT-3'(SEQ ID NO:4970)
5'-AAAGAAAAGAUGAGCAAAGAUGGUA-3'(SEQ ID NO:6674)
3'-UAUUUCUUUUCUACUCGUUUCUACCAU-5'(SEQ ID NO:4485)
KRAS-802靶:5'-ATAAAGAAAAGATGAGCAAAGATGGTA-3'(SEQ ID NO:4971)
5'-AAGUGGUAAUUUUUGUACAUUACAC-3'(SEQ ID NO:6675)
3'-UGUUCACCAUUAAAAACAUGUAAUGUG-5'(SEQ ID NO:4486)
KRAS-908靶:5'-ACAAGTGGTAATTTTTGTACATTACAC-3'(SEQ ID NO:4972)
5'-AGUGGUAAUUUUUGUACAUUACACU-3'(SEQ ID NO:6676)
3'-GUUCACCAUUAAAAACAUGUAAUGUGA-5'(SEQ ID NO:4487)
KRAS-909靶:5'-CAAGTGGTAATTTTTGTACATTACACT-3'(SEQ ID NO:4973)
5'-UUGUACAUUACACUAAAUUAUUAGC-3'(SEQ ID NO:6677)
3'-AAAACAUGUAAUGUGAUUUAAUAAUCG-5'(SEQ ID NO:4488)
KRAS-920靶:5'-TTTTGTACATTACACTAAATTATTAGC-3'(SEQ ID NO:4974)
5'-UGUACAUUACACUAAAUUAUUAGCA-3'(SEQ ID NO:6678)
3'-AAACAUGUAAUGUGAUUUAAUAAUCGU-5'(SEQ ID NO:4489)
KRAS-921靶:5'-TTTGTACATTACACTAAATTATTAGCA-3'(SEQ ID NO:4975)
5'-GUACAUUACACUAAAUUAUUAGCAU-3'(SEQ ID NO:6679)
3'-AACAUGUAAUGUGAUUUAAUAAUCGUA-5'(SEQ ID NO:4490)
KRAS-922靶:5'-TTGTACATTACACTAAATTATTAGCAT-3'(SEQ ID NO:4976)
5'-UACAUUACACUAAAUUAUUAGCAUU-3'(SEQ ID NO:6680)
3'-ACAUGUAAUGUGAUUUAAUAAUCGUAA-5'(SEQ ID NO:4491)
KRAS-923靶:5'-TGTACATTACACTAAATTATTAGCATT-3'(SEQ ID NO:4977)
5'-ACAUUACACUAAAUUAUUAGCAUUU-3'(SEQ ID NO:6681)
3'-CAUGUAAUGUGAUUUAAUAAUCGUAAA-5'(SEQ ID NO:4492)
KRAS-924靶:5'-GTACATTACACTAAATTATTAGCATTT-3'(SEQ ID NO:4978)
5'-CAUUACACUAAAUUAUUAGCAUUUG-3'(SEQ ID NO:6682)
3'-AUGUAAUGUGAUUUAAUAAUCGUAAAC-5'(SEQ ID NO:4493)
KRAS-925靶:5'-TACATTACACTAAATTATTAGCATTTG-3'(SEQ ID NO:4979)
5'-AUUACACUAAAUUAUUAGCAUUUGU-3'(SEQ ID NO:6683)
3'-UGUAAUGUGAUUUAAUAAUCGUAAACA-5'(SEQ ID NO:4494)
KRAS-926靶:5'-ACATTACACTAAATTATTAGCATTTGT-3'(SEQ ID NO:4980)
5'-UUACACUAAAUUAUUAGCAUUUGUU-3'(SEQ ID NO:6684)
3'-GUAAUGUGAUUUAAUAAUCGUAAACAA-5'(SEQ ID NO:4495)
KRAS-927靶:5'-CATTACACTAAATTATTAGCATTTGTT-3'(SEQ ID NO:4981)
5'-UACACUAAAUUAUUAGCAUUUGUUU-3'(SEQ ID NO:6685)
3'-UAAUGUGAUUUAAUAAUCGUAAACAAA-5'(SEQ ID NO:4496)
KRAS-928靶:5'-ATTACACTAAATTATTAGCATTTGTTT-3'(SEQ ID NO:4982)
5'-UAUUAGCAUUUGUUUUAGCAUUACC-3'(SEQ ID NO:6686)
3'-UAAUAAUCGUAAACAAAAUCGUAAUGG-5'(SEQ ID NO:4497)
KRAS-938靶:5'-ATTATTAGCATTTGTTTTAGCATTACC-3'(SEQ ID NO:4983)
5'-AUUAGCAUUUGUUUUAGCAUUACCU-3'(SEQ ID NO:6687)
3'-AAUAAUCGUAAACAAAAUCGUAAUGGA-5'(SEQ ID NO:4498)
KRAS-939靶:5'-TTATTAGCATTTGTTTTAGCATTACCT-3'(SEQ ID NO:4984)
5'-UUAGCAUUUGUUUUAGCAUUACCUA-3'(SEQ ID NO:6688)
3'-AUAAUCGUAAACAAAAUCGUAAUGGAU-5'(SEQ ID NO:4499)
KRAS-940靶:5'-TATTAGCATTTGTTTTAGCATTACCTA-3'(SEQ ID NO:4985)
5'-UAGCAUUUGUUUUAGCAUUACCUAA-3'(SEQ ID NO:6689)
3'-UAAUCGUAAACAAAAUCGUAAUGGAUU-5'(SEQ ID NO:4500)
KRAS-941靶:5'-ATTAGCATTTGTTTTAGCATTACCTAA-3'(SEQ ID NO:4986)
5'-AGCAUUUGUUUUAGCAUUACCUAAU-3'(SEQ ID NO:6690)
3'-AAUCGUAAACAAAAUCGUAAUGGAUUA-5'(SEQ ID NO:4501)
KRAS-942靶:5'-TTAGCATTTGTTTTAGCATTACCTAAT-3'(SEQ ID NO:4987)
5'-GCAUUUGUUUUAGCAUUACCUAAUU-3'(SEQ ID NO:6691)
3'-AUCGUAAACAAAAUCGUAAUGGAUUAA-5'(SEQ ID NO:4502)
KRAS-943靶:5'-TAGCATTTGTTTTAGCATTACCTAATT-3'(SEQ ID NO:4988)
5'-CAUUUGUUUUAGCAUUACCUAAUUU-3'(SEQ ID NO:6692)
3'-UCGUAAACAAAAUCGUAAUGGAUUAAA-5'(SEQ ID NO:4503)
KRAS-944靶:5'-AGCATTTGTTTTAGCATTACCTAATTT-3'(SEQ ID NO:4989)
5'-AUUUGUUUUAGCAUUACCUAAUUUU-3'(SEQ ID NO:6693)
3'-CGUAAACAAAAUCGUAAUGGAUUAAAA-5'(SEQ ID NO:4504)
KRAS-945靶:5'-GCATTTGTTTTAGCATTACCTAATTTT-3'(SEQ ID NO:4990)
5'-UUUGUUUUAGCAUUACCUAAUUUUU-3'(SEQ ID NO:6694)
3'-GUAAACAAAAUCGUAAUGGAUUAAAAA-5'(SEQ ID NO:4505)
KRAS-946靶:5'-CATTTGTTTTAGCATTACCTAATTTTT-3'(SEQ ID NO:4991)
5'-CUUAUUUUAAAAUGACAGUGGAAGU-3'(SEQ ID NO:6695)
3'-ACGAAUAAAAUUUUACUGUCACCUUCA-5'(SEQ ID NO:4506)
KRAS-1010靶:5'-TGCTTATTTTAAAATGACAGTGGAAGT-3'(SEQ ID NO:4992)
5'-UAUUUUAAAAUGACAGUGGAAGUUU-3'(SEQ ID NO:6696)
3'-GAAUAAAAUUUUACUGUCACCUUCAAA-5'(SEQ ID NO:4507)
KRAS-1012靶:5'-CTTATTTTAAAATGACAGTGGAAGTTT-3'(SEQ ID NO:4993)
5'-UCUAAGUGCCAGUAUUCCCAGAGUU-3'(SEQ ID NO:6697)
3'-GGAGAUUCACGGUCAUAAGGGUCUCAA-5'(SEQ ID NO:4508)
KRAS-1045靶:5'-CCTCTAAGTGCCAGTATTCCCAGAGTT-3'(SEQ ID NO:4994)
5'-CAAAUUAAUGAAGCUUUUGAAUCAU-3'(SEQ ID NO:6698)
3'-UUGUUUAAUUACUUCGAAAACUUAGUA-5'(SEQ ID NO:4509)
KRAS-1197靶:5'-AACAAATTAATGAAGCTTTTGAATCAT-3'(SEQ ID NO:4995)
5'-AAAUUAAUGAAGCUUUUGAAUCAUC-3'(SEQ ID NO:6699)
3'-UGUUUAAUUACUUCGAAAACUUAGUAG-5'(SEQ ID NO:4510)
KRAS-1198靶:5'-ACAAATTAATGAAGCTTTTGAATCATC-3'(SEQ ID NO:4996)
5'-UGUGUUUUAUCUAGUCACAUAAAUG-3'(SEQ ID NO:6700)
3'-AGACACAAAAUAGAUCAGUGUAUUUAC-5'(SEQ ID NO:4511)
KRAS-1230靶:5'-TCTGTGTTTTATCTAGTCACATAAATG-3'(SEQ ID NO:4997)
5'-GUGUUUUAUCUAGUCACAUAAAUGG-3'(SEQ ID NO:6701)
3'-GACACAAAAUAGAUCAGUGUAUUUACC-5'(SEQ ID NO:4512)
KRAS-1231靶:5'-CTGTGTTTTATCTAGTCACATAAATGG-3'(SEQ ID NO:4998)
5'-UUUUAUCUAGUCACAUAAAUGGAUU-3'(SEQ ID NO:6702)
3'-ACAAAAUAGAUCAGUGUAUUUACCUAA-5'(SEQ ID NO:4513)
KRAS-1234靶:5'-TGTTTTATCTAGTCACATAAATGGATT-3'(SEQ ID NO:4999)
5'-UAAAUGGAUUAAUUACUAAUUUCAG-3'(SEQ ID NO:6703)
3'-GUAUUUACCUAAUUAAUGAUUAAAGUC-5'(SEQ ID NO:4514)
KRAS-1249靶:5'-CATAAATGGATTAATTACTAATTTCAG-3'(SEQ ID NO:5000)
5'-AAAUGGAUUAAUUACUAAUUUCAGU-3'(SEQ ID NO:6704)
3'-UAUUUACCUAAUUAAUGAUUAAAGUCA-5'(SEQ ID NO:4515)
KRAS-1250靶:5'-ATAAATGGATTAATTACTAATTTCAGT-3'(SEQ ID NO:5001)
5'-AUUGGUUUUUACUGAAACAUUGAGG-3'(SEQ ID NO:6705)
3'-AUUAACCAAAAAUGACUUUGUAACUCC-5'(SEQ ID NO:4516)
KRAS-1287靶:5'-TAATTGGTTTTTACTGAAACATTGAGG-3'(SEQ ID NO:5002)
5'-CAUUUCCUUUUCACAUUAGAUAAAU-3'(SEQ ID NO:6706)
3'-CGGUAAAGGAAAAGUGUAAUCUAUUUA-5'(SEQ ID NO:4517)
KRAS-1527靶:5'-GCCATTTCCTTTTCACATTAGATAAAT-3'(SEQ ID NO:5003)
5'-CUUUUCACAUUAGAUAAAUUACUAU-3'(SEQ ID NO:6707)
3'-AGGAAAAGUGUAAUCUAUUUAAUGAUA-5'(SEQ ID NO:4518)
KRAS-1533靶:5'-TCCTTTTCACATTAGATAAATTACTAT-3'(SEQ ID NO:5004)
5'-CAUUAGAUAAAUUACUAUAAAGACU-3'(SEQ ID NO:6708)
3'-GUGUAAUCUAUUUAAUGAUAUUUCUGA-5'(SEQ ID NO:4519)
KRAS-1540靶:5'-CACATTAGATAAATTACTATAAAGACT-3'(SEQ ID NO:5005)
5'-AUUAGAUAAAUUACUAUAAAGACUC-3'(SEQ ID NO:6709)
3'-UGUAAUCUAUUUAAUGAUAUUUCUGAG-5'(SEQ ID NO:4520)
KRAS-1541靶:5'-ACATTAGATAAATTACTATAAAGACTC-3'(SEQ ID NO:5006)
5'-UUAGAUAAAUUACUAUAAAGACUCC-3'(SEQ ID NO:6710)
3'-GUAAUCUAUUUAAUGAUAUUUCUGAGG-5'(SEQ ID NO:4521)
KRAS-1542靶:5'-CATTAGATAAATTACTATAAAGACTCC-3'(SEQ ID NO:5007)
5'-UAAGGCAGACCCAGUAUGAAAUGGG-3'(SEQ ID NO:6711)
3'-CAAUUCCGUCUGGGUCAUACUUUACCC-5'(SEQ ID NO:4522)
KRAS-1583靶:5'-GTTAAGGCAGACCCAGTATGAAATGGG-3'(SEQ ID NO:5008)
5'-AAGGCAGACCCAGUAUGAAAUGGGG-3'(SEQ ID NO:6712)
3'-AAUUCCGUCUGGGUCAUACUUUACCCC-5'(SEQ ID NO:4523)
KRAS-1584靶:5'-TTAAGGCAGACCCAGTATGAAATGGGG-3'(SEQ ID NO:5009)
5'-AGGCAGACCCAGUAUGAAAUGGGGA-3'(SEQ ID NO:6713)
3'-AUUCCGUCUGGGUCAUACUUUACCCCU-5'(SEQ ID NO:4524)
KRAS-1585靶:5'-TAAGGCAGACCCAGTATGAAATGGGGA-3'(SEQ ID NO:5010)
5'-GGCAGACCCAGUAUGAAAUGGGGAU-3'(SEQ ID NO:6714)
3'-UUCCGUCUGGGUCAUACUUUACCCCUA-5'(SEQ ID NO:4525)
KRAS-1586靶:5'-AAGGCAGACCCAGTATGAAATGGGGAT-3'(SEQ ID NO:5011)
5'-UAUGAAAUGGGGAUUAUUAUAGCAA-3'(SEQ ID NO:6715)
3'-UCAUACUUUACCCCUAAUAAUAUCGUU-5'(SEQ ID NO:4526)
KRAS-1597靶:5'-AGTATGAAATGGGGATTATTATAGCAA-3'(SEQ ID NO:5012)
5'-GGGAUUAUUAUAGCAACCAUUUUGG-3'(SEQ ID NO:6716)
3'-ACCCCUAAUAAUAUCGUUGGUAAAACC-5'(SEQ ID NO:4527)
KRAS-1606靶:5'-TGGGGATTATTATAGCAACCATTTTGG-3'(SEQ ID NO:5013)
5'-GGGCUAUAUUUACAUGCUACUAAAU-3'(SEQ ID NO:6717)
3'-ACCCCGAUAUAAAUGUACGAUGAUUUA-5'(SEQ ID NO:4528)
KRAS-1630靶:5'-TGGGGCTATATTTACATGCTACTAAAT-3'(SEQ ID NO:5014)
5'-GGCUAUAUUUACAUGCUACUAAAUU-3'(SEQ ID NO:6718)
3'-CCCCGAUAUAAAUGUACGAUGAUUUAA-5'(SEQ ID NO:4529)
KRAS-1631靶:5'-GGGGCTATATTTACATGCTACTAAATT-3'(SEQ ID NO:5015)
5'-GCUAUAUUUACAUGCUACUAAAUUU-3'(SEQ ID NO:6719)
3'-CCCGAUAUAAAUGUACGAUGAUUUAAA-5'(SEQ ID NO:4530)
KRAS-1632靶:5'-GGGCTATATTTACATGCTACTAAATTT-3'(SEQ ID NO:5016)
5'-CUAUAUUUACAUGCUACUAAAUUUU-3'(SEQ ID NO:6720)
3'-CCGAUAUAAAUGUACGAUGAUUUAAAA-5'(SEQ ID NO:4531)
KRAS-1633靶:5'-GGCTATATTTACATGCTACTAAATTTT-3'(SEQ ID NO:5017)
5'-UAUAUUUACAUGCUACUAAAUUUUU-3'(SEQ ID NO:6721)
3'-CGAUAUAAAUGUACGAUGAUUUAAAAA-5'(SEQ ID NO:4532)
KRAS-1634靶:5'-GCTATATTTACATGCTACTAAATTTTT-3'(SEQ ID NO:5018)
5'-AUAUUUACAUGCUACUAAAUUUUUA-3'(SEQ ID NO:6722)
3'-GAUAUAAAUGUACGAUGAUUUAAAAAU-5'(SEQ ID NO:4533)
KRAS-1635靶:5'-CTATATTTACATGCTACTAAATTTTTA-3'(SEQ ID NO:5019)
5'-UAUUUACAUGCUACUAAAUUUUUAU-3'(SEQ ID NO:6723)
3'-AUAUAAAUGUACGAUGAUUUAAAAAUA-5'(SEQ ID NO:4534)
KRAS-1636靶:5'-TATATTTACATGCTACTAAATTTTTAT-3'(SEQ ID NO:5020)
5'-AUUUACAUGCUACUAAAUUUUUAUA-3'(SEQ ID NO:6724)
3'-UAUAAAUGUACGAUGAUUUAAAAAUAU-5'(SEQ ID NO:4535)
KRAS-1637靶:5'-ATATTTACATGCTACTAAATTTTTATA-3'(SEQ ID NO:5021)
5'-UUUACAUGCUACUAAAUUUUUAUAA-3'(SEQ ID NO:6725)
3'-AUAAAUGUACGAUGAUUUAAAAAUAUU-5'(SEQ ID NO:4536)
KRAS-1638靶:5'-TATTTACATGCTACTAAATTTTTATAA-3'(SEQ ID NO:5022)
5'-UUACAUGCUACUAAAUUUUUAUAAU-3'(SEQ ID NO:6726)
3'-UAAAUGUACGAUGAUUUAAAAAUAUUA-5'(SEQ ID NO:4537)
KRAS-1639靶:5'-ATTTACATGCTACTAAATTTTTATAAT-3'(SEQ ID NO:5023)
5'-UACAUGCUACUAAAUUUUUAUAAUA-3'(SEQ ID NO:6727)
3'-AAAUGUACGAUGAUUUAAAAAUAUUAU-5'(SEQ ID NO:4538)
KRAS-1640靶:5'-TTTACATGCTACTAAATTTTTATAATA-3'(SEQ ID NO:5024)
5'-CUUUCAUAGUAUAACUUUAAAUCUU-3'(SEQ ID NO:6728)
3'-GAGAAAGUAUCAUAUUGAAAUUUAGAA-5'(SEQ ID NO:4539)
KRAS-1736靶:5'-CTCTTTCATAGTATAACTTTAAATCTT-3'(SEQ ID NO:5025)
5'-AUAGUAUAACUUUAAAUCUUUUCUU-3'(SEQ ID NO:6729)
3'-AGUAUCAUAUUGAAAUUUAGAAAAGAA-5'(SEQ ID NO:4540)
KRAS-1741靶:5'-TCATAGTATAACTTTAAATCTTTTCTT-3'(SEQ ID NO:5026)
5'-UAGUAUAACUUUAAAUCUUUUCUUC-3'(SEQ ID NO:6730)
3'-GUAUCAUAUUGAAAUUUAGAAAAGAAG-5'(SEQ ID NO:4541)
KRAS-1742靶:5'-CATAGTATAACTTTAAATCTTTTCTTC-3'(SEQ ID NO:5027)
5'-UAAAUCUUUUCUUCAACUUGAGUCU-3'(SEQ ID NO:6731)
3'-AAAUUUAGAAAAGAAGUUGAACUCAGA-5'(SEQ ID NO:4542)
KRAS-1753靶:5'-TTTAAATCTTTTCTTCAACTTGAGTCT-3'(SEQ ID NO:5028)
5'-AAAUCUUUUCUUCAACUUGAGUCUU-3'(SEQ ID NO:6732)
3'-AAUUUAGAAAAGAAGUUGAACUCAGAA-5'(SEQ ID NO:4543)
KRAS-1754靶:5'-TTAAATCTTTTCTTCAACTTGAGTCTT-3'(SEQ ID NO:5029)
5'-CUUGAGUCUUUGAAGAUAGUUUUAA-3'(SEQ ID NO:6733)
3'-UUGAACUCAGAAACUUCUAUCAAAAUU-5'(SEQ ID NO:4544)
KRAS-1769靶:5'-AACTTGAGTCTTTGAAGATAGTTTTAA-3'(SEQ ID NO:5030)
5'-UGAGUCUUUGAAGAUAGUUUUAAUU-3'(SEQ ID NO:6734)
3'-GAACUCAGAAACUUCUAUCAAAAUUAA-5'(SEQ ID NO:4545)
KRAS-1771靶:5'-CTTGAGTCTTTGAAGATAGTTTTAATT-3'(SEQ ID NO:5031)
5'-GAGUCUUUGAAGAUAGUUUUAAUUC-3'(SEQ ID NO:6735)
3'-AACUCAGAAACUUCUAUCAAAAUUAAG-5'(SEQ ID NO:4546)
KRAS-1772靶:5'-TTGAGTCTTTGAAGATAGTTTTAATTC-3'(SEQ ID NO:5032)
5'-GAUAGUUUUAAUUCUGCUUGUGACA-3'(SEQ ID NO:6736)
3'-UUCUAUCAAAAUUAAGACGAACACUGU-5'(SEQ ID NO:4547)
KRAS-1783靶:5'-AAGATAGTTTTAATTCTGCTTGTGACA-3'(SEQ ID NO:5033)
5'-AUAGUUUUAAUUCUGCUUGUGACAU-3'(SEQ ID NO:6737)
3'-UCUAUCAAAAUUAAGACGAACACUGUA-5'(SEQ ID NO:4548)
KRAS-1784靶:5'-AGATAGTTTTAATTCTGCTTGTGACAT-3'(SEQ ID NO:5034)
5'-UAGUUUUAAUUCUGCUUGUGACAUU-3'(SEQ ID NO:6738)
3'-CUAUCAAAAUUAAGACGAACACUGUAA-5'(SEQ ID NO:4549)
KRAS-1785靶:5'-GATAGTTTTAATTCTGCTTGTGACATT-3'(SEQ ID NO:5035)
5'-CUUGUGACAUUAAAAGAUUAUUUGG-3'(SEQ ID NO:6739)
3'-ACGAACACUGUAAUUUUCUAAUAAACC-5'(SEQ ID NO:4550)
KRAS-1799靶:5'-TGCTTGTGACATTAAAAGATTATTTGG-3'(SEQ ID NO:5036)
5'-UAUUAACUCAAAAGUUGAGAUUUUG-3'(SEQ ID NO:6740)
3'-UUAUAAUUGAGUUUUCAACUCUAAAAC-5'(SEQ ID NO:4551)
KRAS-2100靶:5'-AATATTAACTCAAAAGTTGAGATTTTG-3'(SEQ ID NO:5037)
5'-UGUGCCAAGACAUUAAUUUUUUUUU-3'(SEQ ID NO:6741)
3'-CCACACGGUUCUGUAAUUAAAAAAAAA-5'(SEQ ID NO:4552)
KRAS-2134靶:5'-GGTGTGCCAAGACATTAATTTTTTTTT-3'(SEQ ID NO:5038)
5'-UGGUUAAAUUAACAUUGCAUAAACA-3'(SEQ ID NO:6742)
3'-UGACCAAUUUAAUUGUAACGUAUUUGU-5'(SEQ ID NO:4553)
KRAS-2216靶:5'-ACTGGTTAAATTAACATTGCATAAACA-3'(SEQ ID NO:5039)
5'-GGUUAAAUUAACAUUGCAUAAACAC-3'(SEQ ID NO:6743)
3'-GACCAAUUUAAUUGUAACGUAUUUGUG-5'(SEQ ID NO:4554)
KRAS-2217靶:5'-CTGGTTAAATTAACATTGCATAAACAC-3'(SEQ ID NO:5040)
5'-GUUAAAUUAACAUUGCAUAAACACU-3'(SEQ ID NO:6744)
3'-ACCAAUUUAAUUGUAACGUAUUUGUGA-5'(SEQ ID NO:4555)
KRAS-2218靶:5'-TGGTTAAATTAACATTGCATAAACACT-3'(SEQ ID NO:5041)
5'-AUUGCAUAAACACUUUUCAAGUCUG-3'(SEQ ID NO:6745)
3'-UGUAACGUAUUUGUGAAAAGUUCAGAC-5'(SEQ ID NO:4556)
KRAS-2229靶:5'-ACATTGCATAAACACTTTTCAAGTCTG-3'(SEQ ID NO:5042)
5'-AAGUCUGAUCCAUAUUUAAUAAUGC-3'(SEQ ID NO:6746)
3'-AGUUCAGACUAGGUAUAAAUUAUUACG-5'(SEQ ID NO:4557)
KRAS-2247靶:5'-TCAAGTCTGATCCATATTTAATAATGC-3'(SEQ ID NO:5043)
5'-UAAAAUAAAUGAAGUGAGAUGGCAU-3'(SEQ ID NO:6747)
3'-AAAUUUUAUUUACUUCACUCUACCGUA-5'(SEQ ID NO:4558)
KRAS-2326靶:5'-TTTAAAATAAATGAAGTGAGATGGCAT-3'(SEQ ID NO:5044)
5'-AAAAUAAAUGAAGUGAGAUGGCAUG-3'(SEQ ID NO:6748)
3'-AAUUUUAUUUACUUCACUCUACCGUAC-5'(SEQ ID NO:4559)
KRAS-2327靶:5'-TTAAAATAAATGAAGTGAGATGGCATG-3'(SEQ ID NO:5045)
5'-AAGCUCAGCACAAUCUGUAAAUUUU-3'(SEQ ID NO:6749)
3'-AGUUCGAGUCGUGUUAGACAUUUAAAA-5'(SEQ ID NO:4560)
KRAS-2547靶:5'-TCAAGCTCAGCACAATCTGTAAATTTT-3'(SEQ ID NO:5046)
5'-AGCUCAGCACAAUCUGUAAAUUUUU-3'(SEQ ID NO:6750)
3'-GUUCGAGUCGUGUUAGACAUUUAAAAA-5'(SEQ ID NO:4561)
KRAS-2548靶:5'-CAAGCTCAGCACAATCTGTAAATTTTT-3'(SEQ ID NO:5047)
5'-AUAACUGUGAUUCUUUUAGGACAAU-3'(SEQ ID NO:6751)
3'-CGUAUUGACACUAAGAAAAUCCUGUUA-5'(SEQ ID NO:4562)
KRAS-3741靶:5'-GCATAACTGTGATTCTTTTAGGACAAT-3'(SEQ ID NO:5048)
5'-UGUGAUUCUUUUAGGACAAUUACUG-3'(SEQ ID NO:6752)
3'-UGACACUAAGAAAAUCCUGUUAAUGAC-5'(SEQ ID NO:4563)
KRAS-3746靶:5'-ACTGTGATTCTTTTAGGACAATTACTG-3'(SEQ ID NO:5049)
5'-GUGAUUCUUUUAGGACAAUUACUGU-3'(SEQ ID NO:6753)
3'-GACACUAAGAAAAUCCUGUUAAUGACA-5'(SEQ ID NO:4564)
KRAS-3747靶:5'-CTGTGATTCTTTTAGGACAATTACTGT-3'(SEQ ID NO:5050)
5'-UGUAUGUCAGAUAUUCAUAUUGACC-3'(SEQ ID NO:6754)
3'-CCACAUACAGUCUAUAAGUAUAACUGG-5'(SEQ ID NO:4565)
KRAS-3783靶:5'-GGTGTATGTCAGATATTCATATTGACC-3'(SEQ ID NO:5051)
5'-GUAUGUCAGAUAUUCAUAUUGACCC-3'(SEQ ID NO:6755)
3'-CACAUACAGUCUAUAAGUAUAACUGGG-5'(SEQ ID NO:4566)
KRAS-3784靶:5'-GTGTATGTCAGATATTCATATTGACCC-3'(SEQ ID NO:5052)
5'-AAUGUGUAAUAUUCCAGUUUUCUCU-3'(SEQ ID NO:6756)
3'-GUUUACACAUUAUAAGGUCAAAAGAGA-5'(SEQ ID NO:4567)
KRAS-3810靶:5'-CAAATGTGTAATATTCCAGTTTTCTCT-3'(SEQ ID NO:5053)
5'-CACUGCAUAGGAAUUUAGAACCUAA-3'(SEQ ID NO:6757)
3'-GUGUGACGUAUCCUUAAAUCUUGGAUU-5'(SEQ ID NO:4568)
KRAS-4396靶:5'-CACACTGCATAGGAATTTAGAACCTAA-3'(SEQ ID NO:5054)
5'-CACCAUUGCACAAUUUUGUCCUAAU-3'(SEQ ID NO:6758)
3'-CAGUGGUAACGUGUUAAAACAGGAUUA-5'(SEQ ID NO:4569)
KRAS-4447靶:5'-GTCACCATTGCACAATTTTGTCCTAAT-3'(SEQ ID NO:5055)
5'-ACCAUUGCACAAUUUUGUCCUAAUA-3'(SEQ ID NO:6759)
3'-AGUGGUAACGUGUUAAAACAGGAUUAU-5'(SEQ ID NO:4570)
KRAS-4448靶:5'-TCACCATTGCACAATTTTGTCCTAATA-3'(SEQ ID NO:5056)
5'-CCAUUGCACAAUUUUGUCCUAAUAU-3'(SEQ ID NO:6760)
3'-GUGGUAACGUGUUAAAACAGGAUUAUA-5'(SEQ ID NO:4571)
KRAS-4449靶:5'-CACCATTGCACAATTTTGTCCTAATAT-3'(SEQ ID NO:5057)
5'-CAUUGCACAAUUUUGUCCUAAUAUA-3'(SEQ ID NO:6761)
3'-UGGUAACGUGUUAAAACAGGAUUAUAU-5'(SEQ ID NO:4572)
KRAS-4450靶:5'-ACCATTGCACAATTTTGTCCTAATATA-3'(SEQ ID NO:5058)
5'-AUUGCACAAUUUUGUCCUAAUAUAU-3'(SEQ ID NO:6762)
3'-GGUAACGUGUUAAAACAGGAUUAUAUA-5'(SEQ ID NO:4573)
KRAS-4451靶:5'-CCATTGCACAATTTTGTCCTAATATAT-3'(SEQ ID NO:5059)
5'-UUGCACAAUUUUGUCCUAAUAUAUA-3'(SEQ ID NO:6763)
3'-GUAACGUGUUAAAACAGGAUUAUAUAU-5'(SEQ ID NO:4574)
KRAS-4452靶:5'-CATTGCACAATTTTGTCCTAATATATA-3'(SEQ ID NO:5060)
5'-UAGCAUGAAUUCUGCAUUGAGAAAC-3'(SEQ ID NO:6764)
3'-CUAUCGUACUUAAGACGUAACUCUUUG-5'(SEQ ID NO:4575)
KRAS-4748靶:5'-GATAGCATGAATTCTGCATTGAGAAAC-3'(SEQ ID NO:5061)
5'-AGCAUGAAUUCUGCAUUGAGAAACU-3'(SEQ ID NO:6765)
3'-UAUCGUACUUAAGACGUAACUCUUUGA-5'(SEQ ID NO:4576)
KRAS-4749靶:5'-ATAGCATGAATTCTGCATTGAGAAACT-3'(SEQ ID NO:5062)
5'-UUUGAAGUGCCUGUUUGGGAUAAUG-3'(SEQ ID NO:6766)
3'-UCAAACUUCACGGACAAACCCUAUUAC-5'(SEQ ID NO:4577)
KRAS-4878靶:5'-AGTTTGAAGTGCCTGTTTGGGATAATG-3'(SEQ ID NO:5063)
5'-UUGAAGUGCCUGUUUGGGAUAAUGA-3'(SEQ ID NO:6767)
3'-CAAACUUCACGGACAAACCCUAUUACU-5'(SEQ ID NO:4578)
KRAS-4879靶:5'-GTTTGAAGTGCCTGTTTGGGATAATGA-3'(SEQ ID NO:5064)
5'-UGAAGUGCCUGUUUGGGAUAAUGAU-3'(SEQ ID NO:6768)
3'-AAACUUCACGGACAAACCCUAUUACUA-5'(SEQ ID NO:4579)
KRAS-4880靶:5'-TTTGAAGTGCCTGTTTGGGATAATGAT-3'(SEQ ID NO:5065)
5'-UUUGAGUGCCAAUUUCUUACUAGUA-3'(SEQ ID NO:6769)
3'-GGAAACUCACGGUUAAAGAAUGAUCAU-5'(SEQ ID NO:4580)
KRAS-5073靶:5'-CCTTTGAGTGCCAATTTCTTACTAGTA-3'(SEQ ID NO:5066)
5'-UUGAGUGCCAAUUUCUUACUAGUAC-3'(SEQ ID NO:6770)
3'-GAAACUCACGGUUAAAGAAUGAUCAUG-5'(SEQ ID NO:4581)
KRAS-5074靶:5'-CTTTGAGTGCCAATTTCTTACTAGTAC-3'(SEQ ID NO:5067)
5'-UGAGUGCCAAUUUCUUACUAGUACU-3'(SEQ ID NO:6771)
3'-AAACUCACGGUUAAAGAAUGAUCAUGA-5'(SEQ ID NO:4582)
KRAS-5075靶:5'-TTTGAGTGCCAATTTCTTACTAGTACT-3'(SEQ ID NO:5068)
5'-GAGUGCCAAUUUCUUACUAGUACUA-3'(SEQ ID NO:6772)
3'-AACUCACGGUUAAAGAAUGAUCAUGAU-5'(SEQ ID NO:4583)
KRAS-5076靶:5'-TTGAGTGCCAATTTCTTACTAGTACTA-3'(SEQ ID NO:5069)
5'-AGUGCCAAUUUCUUACUAGUACUAU-3'(SEQ ID NO:6773)
3'-ACUCACGGUUAAAGAAUGAUCAUGAUA-5'(SEQ ID NO:4584)
KRAS-5077靶:5'-TGAGTGCCAATTTCTTACTAGTACTAT-3'(SEQ ID NO:5070)
5'-GUGCCAAUUUCUUACUAGUACUAUU-3'(SEQ ID NO:6774)
3'-CUCACGGUUAAAGAAUGAUCAUGAUAA-5'(SEQ ID NO:4585)
KRAS-5078靶:5'-GAGTGCCAATTTCTTACTAGTACTATT-3'(SEQ ID NO:5071)
5'-AUGUAUUUUAACUAUUUUUGUAUAG-3'(SEQ ID NO:6775)
3'-CUUACAUAAAAUUGAUAAAAACAUAUC-5'(SEQ ID NO:4586)
KRAS-5128靶:5'-GAATGTATTTTAACTATTTTTGTATAG-3'(SEQ ID NO:5072)
5'-UGUAUUUUAACUAUUUUUGUAUAGU-3'(SEQ ID NO:6776)
3'-UUACAUAAAAUUGAUAAAAACAUAUCA-5'(SEQ ID NO:4587)
KRAS-5129靶:5'-AATGTATTTTAACTATTTTTGTATAGT-3'(SEQ ID NO:5073)
5'-ACUAUUUUUGUAUAGUGUAAACUGA-3'(SEQ ID NO:6777)
3'-AUUGAUAAAAACAUAUCACAUUUGACU-5'(SEQ ID NO:4588)
KRAS-5138靶:5'-TAACTATTTTTGTATAGTGTAAACTGA-3'(SEQ ID NO:5074)
5'-CUAUUUUUGUAUAGUGUAAACUGAA-3'(SEQ ID NO:6778)
3'-UUGAUAAAAACAUAUCACAUUUGACUU-5'(SEQ ID NO:4589)
KRAS-5139靶:5'-AACTATTTTTGTATAGTGTAAACTGAA-3'(SEQ ID NO:5075)
5'-UAUUUUUGUAUAGUGUAAACUGAAA-3'(SEQ ID NO:6779)
3'-UGAUAAAAACAUAUCACAUUUGACUUU-5'(SEQ ID NO:4590)
KRAS-5140靶:5'-ACTATTTTTGTATAGTGTAAACTGAAA-3'(SEQ ID NO:5076)
5'-AUUUUUGUAUAGUGUAAACUGAAAC-3'(SEQ ID NO:6780)
3'-GAUAAAAACAUAUCACAUUUGACUUUG-5'(SEQ ID NO:4591)
KRAS-5141靶:5'-CTATTTTTGTATAGTGTAAACTGAAAC-3'(SEQ ID NO:5077)
5'-UUUUUGUAUAGUGUAAACUGAAACA-3'(SEQ ID NO:6781)
3'-AUAAAAACAUAUCACAUUUGACUUUGU-5'(SEQ ID NO:4592)
KRAS-5142靶:5'-TATTTTTGTATAGTGTAAACTGAAACA-3'(SEQ ID NO:5078)
5'-UUUUGUAUAGUGUAAACUGAAACAU-3'(SEQ ID NO:6782)
3'-UAAAAACAUAUCACAUUUGACUUUGUA-5'(SEQ ID NO:4593)
KRAS-5143靶:5'-ATTTTTGTATAGTGTAAACTGAAACAT-3'(SEQ ID NO:5079)
5'-AACAUGCACAUUUUGUACAUUGUGC-3'(SEQ ID NO:6783)
3'-CUUUGUACGUGUAAAACAUGUAACACG-5'(SEQ ID NO:4594)
KRAS-5163靶:5'-GAAACATGCACATTTTGTACATTGTGC-3'(SEQ ID NO:5080)
5'-ACAUGCACAUUUUGUACAUUGUGCU-3'(SEQ ID NO:6784)
3'-UUUGUACGUGUAAAACAUGUAACACGA-5'(SEQ ID NO:4595)
KRAS-5164靶:5'-AAACATGCACATTTTGTACATTGTGCT-3'(SEQ ID NO:5081)
5'-UGCACAUUUUGUACAUUGUGCUUUC-3'(SEQ ID NO:6785)
3'-GUACGUGUAAAACAUGUAACACGAAAG-5'(SEQ ID NO:4596)
KRAS-5167靶:5'-CATGCACATTTTGTACATTGTGCTTTC-3'(SEQ ID NO:5082)
5'-GCACAUUUUGUACAUUGUGCUUUCU-3'(SEQ ID NO:6786)
3'-UACGUGUAAAACAUGUAACACGAAAGA-5'(SEQ ID NO:4597)
KRAS-5168靶:5'-ATGCACATTTTGTACATTGTGCTTTCT-3'(SEQ ID NO:5083)
5'-CACAUUUUGUACAUUGUGCUUUCUU-3'(SEQ ID NO:6787)
3'-ACGUGUAAAACAUGUAACACGAAAGAA-5'(SEQ ID NO:4598)
KRAS-5169靶:5'-TGCACATTTTGTACATTGTGCTTTCTT-3'(SEQ ID NO:5084)
5'-ACAUUUUGUACAUUGUGCUUUCUUU-3'(SEQ ID NO:6788)
3'-CGUGUAAAACAUGUAACACGAAAGAAA-5'(SEQ ID NO:4599)
KRAS-5170靶:5'-GCACATTTTGTACATTGTGCTTTCTTT-3'(SEQ ID NO:5085)
5'-CAUUUUGUACAUUGUGCUUUCUUUU-3'(SEQ ID NO:6789)
3'-GUGUAAAACAUGUAACACGAAAGAAAA-5'(SEQ ID NO:4600)
KRAS-5171靶:5'-CACATTTTGTACATTGTGCTTTCTTTT-3'(SEQ ID NO:5086)
5'-AUUUUGUACAUUGUGCUUUCUUUUG-3'(SEQ ID NO:6790)
3'-UGUAAAACAUGUAACACGAAAGAAAAC-5'(SEQ ID NO:4601)
KRAS-5172靶:5'-ACATTTTGTACATTGTGCTTTCTTTTG-3'(SEQ ID NO:5087)
5'-UUUUGUACAUUGUGCUUUCUUUUGU-3'(SEQ ID NO:6791)
3'-GUAAAACAUGUAACACGAAAGAAAACA-5'(SEQ ID NO:4602)
KRAS-5173靶:5'-CATTTTGTACATTGTGCTTTCTTTTGT-3'(SEQ ID NO:5088)
5'-UGGGACAUAUGCAGUGUGAUCCAGU-3'(SEQ ID NO:6792)
3'-ACACCCUGUAUACGUCACACUAGGUCA-5'(SEQ ID NO:4603)
KRAS-5197靶:5'-TGTGGGACATATGCAGTGTGATCCAGT-3'(SEQ ID NO:5089)
5'-GGGACAUAUGCAGUGUGAUCCAGUU-3'(SEQ ID NO:6793)
3'-CACCCUGUAUACGUCACACUAGGUCAA-5'(SEQ ID NO:4604)
KRAS-5198靶:5'-GTGGGACATATGCAGTGTGATCCAGTT-3'(SEQ ID NO:5090)
5'-GGACAUAUGCAGUGUGAUCCAGUUG-3'(SEQ ID NO:6794)
3'-ACCCUGUAUACGUCACACUAGGUCAAC-5'(SEQ ID NO:4605)
KRAS-5199靶:5'-TGGGACATATGCAGTGTGATCCAGTTG-3'(SEQ ID NO:5091)
5'-GACAUAUGCAGUGUGAUCCAGUUGU-3'(SEQ ID NO:6795)
3'-CCCUGUAUACGUCACACUAGGUCAACA-5'(SEQ ID NO:4606)
KRAS-5200靶:5'-GGGACATATGCAGTGTGATCCAGTTGT-3'(SEQ ID NO:5092)
5'-ACAUAUGCAGUGUGAUCCAGUUGUU-3'(SEQ ID NO:6796)
3'-CCUGUAUACGUCACACUAGGUCAACAA-5'(SEQ ID NO:4607)
KRAS-5201靶:5'-GGACATATGCAGTGTGATCCAGTTGTT-3'(SEQ ID NO:5093)
5'-CAUAUGCAGUGUGAUCCAGUUGUUU-3'(SEQ ID NO:6797)
3'-CUGUAUACGUCACACUAGGUCAACAAA-5'(SEQ ID NO:4608)
KRAS-5202靶:5'-GACATATGCAGTGTGATCCAGTTGTTT-3'(SEQ ID NO:5094)
5'-AUAUGCAGUGUGAUCCAGUUGUUUU-3'(SEQ ID NO:6798)
3'-UGUAUACGUCACACUAGGUCAACAAAA-5'(SEQ ID NO:4609)
KRAS-5203靶:5'-ACATATGCAGTGTGATCCAGTTGTTTT-3'(SEQ ID NO:5095)
5'-UAUGCAGUGUGAUCCAGUUGUUUUC-3'(SEQ ID NO:6799)
3'-GUAUACGUCACACUAGGUCAACAAAAG-5'(SEQ ID NO:4610)
KRAS-5204靶:5'-CATATGCAGTGTGATCCAGTTGTTTTC-3'(SEQ ID NO:5096)
5'-AUGCAGUGUGAUCCAGUUGUUUUCC-3'(SEQ ID NO:6800)
3'-UAUACGUCACACUAGGUCAACAAAAGG-5'(SEQ ID NO:4611)
KRAS-5205靶:5'-ATATGCAGTGTGATCCAGTTGTTTTCC-3'(SEQ ID NO:5097)
5'-AGUGUGAUCCAGUUGUUUUCCAUCA-3'(SEQ ID NO:6801)
3'-CGUCACACUAGGUCAACAAAAGGUAGU-5'(SEQ ID NO:4612)
KRAS-5209靶:5'-GCAGTGTGATCCAGTTGTTTTCCATCA-3'(SEQ ID NO:5098)
5'-GUGUGAUCCAGUUGUUUUCCAUCAU-3'(SEQ ID NO:6802)
3'-GUCACACUAGGUCAACAAAAGGUAGUA-5'(SEQ ID NO:4613)
KRAS-5210靶:5'-CAGTGTGATCCAGTTGTTTTCCATCAT-3'(SEQ ID NO:5099)
5'-UGUGAUCCAGUUGUUUUCCAUCAUU-3'(SEQ ID NO:6803)
3'-UCACACUAGGUCAACAAAAGGUAGUAA-5'(SEQ ID NO:4614)
KRAS-5211靶:5'-AGTGTGATCCAGTTGTTTTCCATCATT-3'(SEQ ID NO:5100)
5'-GUGAUCCAGUUGUUUUCCAUCAUUU-3'(SEQ ID NO:6804)
3'-CACACUAGGUCAACAAAAGGUAGUAAA-5'(SEQ ID NO:4615)
KRAS-5212靶:5'-GTGTGATCCAGTTGTTTTCCATCATTT-3'(SEQ ID NO:5101)
5'-UGAUCCAGUUGUUUUCCAUCAUUUG-3'(SEQ ID NO:6805)
3'-ACACUAGGUCAACAAAAGGUAGUAAAC-5'(SEQ ID NO:4616)
KRAS-5213靶:5'-TGTGATCCAGTTGTTTTCCATCATTTG-3'(SEQ ID NO:5102)
5'-GAUCCAGUUGUUUUCCAUCAUUUGG-3'(SEQ ID NO:6806)
3'-CACUAGGUCAACAAAAGGUAGUAAACC-5'(SEQ ID NO:4617)
KRAS-5214靶:5'-GTGATCCAGTTGTTTTCCATCATTTGG-3'(SEQ ID NO:5103)
5'-UUUGGUUGCGCUGACCUAGGAAUGU-3'(SEQ ID NO:6807)
3'-GUAAACCAACGCGACUGGAUCCUUACA-5'(SEQ ID NO:4618)
KRAS-5234靶:5'-CATTTGGTTGCGCTGACCTAGGAATGT-3'(SEQ ID NO:5104)
5'-UUGGUUGCGCUGACCUAGGAAUGUU-3'(SEQ ID NO:6808)
3'-UAAACCAACGCGACUGGAUCCUUACAA-5'(SEQ ID NO:4619)
KRAS-5235靶:5'-ATTTGGTTGCGCTGACCTAGGAATGTT-3'(SEQ ID NO:5105)
5'-GGAAUGUUGGUCAUAUCAAACAUUA-3'(SEQ ID NO:6809)
3'-AUCCUUACAACCAGUAUAGUUUGUAAU-5'(SEQ ID NO:4620)
KRAS-5252靶:5'-TAGGAATGTTGGTCATATCAAACATTA-3'(SEQ ID NO:5106)
5'-GAAUGUUGGUCAUAUCAAACAUUAA-3'(SEQ ID NO:6810)
3'-UCCUUACAACCAGUAUAGUUUGUAAUU-5'(SEQ ID NO:4621)
KRAS-5253靶:5'-AGGAATGTTGGTCATATCAAACATTAA-3'(SEQ ID NO:5107)
5'-AAUGUUGGUCAUAUCAAACAUUAAA-3'(SEQ ID NO:6811)
3'-CCUUACAACCAGUAUAGUUUGUAAUUU-5'(SEQ ID NO:4622)
KRAS-5254靶:5'-GGAATGTTGGTCATATCAAACATTAAA-3'(SEQ ID NO:5108)
5'-AUGUUGGUCAUAUCAAACAUUAAAA-3'(SEQ ID NO:6812)
3'-CUUACAACCAGUAUAGUUUGUAAUUUU-5'(SEQ ID NO:4623)
KRAS-5255靶:5'-GAATGTTGGTCATATCAAACATTAAAA-3'(SEQ ID NO:5109)
5'-UGUUGGUCAUAUCAAACAUUAAAAA-3'(SEQ ID NO:6813)
3'-UUACAACCAGUAUAGUUUGUAAUUUUU-5'(SEQ ID NO:4624)
KRAS-5256靶:5'-AATGTTGGTCATATCAAACATTAAAAA-3'(SEQ ID NO:5110)
5'-GUUGGUCAUAUCAAACAUUAAAAAU-3'(SEQ ID NO:6814)
3'-UACAACCAGUAUAGUUUGUAAUUUUUA-5'(SEQ ID NO:4625)
KRAS-5257靶:5'-ATGTTGGTCATATCAAACATTAAAAAT-3'(SEQ ID NO:5111)
5'-UUGGUCAUAUCAAACAUUAAAAAUG-3'(SEQ ID NO:6815)
3'-ACAACCAGUAUAGUUUGUAAUUUUUAC-5'(SEQ ID NO:4626)
KRAS-5258靶:5'-TGTTGGTCATATCAAACATTAAAAATG-3'(SEQ ID NO:5112)
5'-UGGUCAUAUCAAACAUUAAAAAUGA-3'(SEQ ID NO:6816)
3'-CAACCAGUAUAGUUUGUAAUUUUUACU-5'(SEQ ID NO:4627)
KRAS-5259靶:5'-GTTGGTCATATCAAACATTAAAAATGA-3'(SEQ ID NO:5113)
5'-GGUCAUAUCAAACAUUAAAAAUGAC-3'(SEQ ID NO:6817)
3'-AACCAGUAUAGUUUGUAAUUUUUACUG-5'(SEQ ID NO:4628)
KRAS-5260靶:5'-TTGGTCATATCAAACATTAAAAATGAC-3'(SEQ ID NO:5114)
5'-AAAUUAACUUUUAAAUGUUUAUAGG-3'(SEQ ID NO:6818)
3'-ACUUUAAUUGAAAAUUUACAAAUAUCC-5'(SEQ ID NO:4629)
KRAS-5299靶:5'-TGAAATTAACTTTTAAATGTTTATAGG-3'(SEQ ID NO:5115)
5'-AAUUAACUUUUAAAUGUUUAUAGGA-3'(SEQ ID NO:6819)
3'-CUUUAAUUGAAAAUUUACAAAUAUCCU-5'(SEQ ID NO:4630)
KRAS-5300靶:5'-GAAATTAACTTTTAAATGTTTATAGGA-3'(SEQ ID NO:5116)
5'-AACUUUUAAAUGUUUAUAGGAGUAU-3'(SEQ ID NO:6820)
3'-AAUUGAAAAUUUACAAAUAUCCUCAUA-5'(SEQ ID NO:4631)
KRAS-5304靶:5'-TTAACTTTTAAATGTTTATAGGAGTAT-3'(SEQ ID NO:5117)
5'-ACUUUUAAAUGUUUAUAGGAGUAUG-3'(SEQ ID NO:6821)
3'-AUUGAAAAUUUACAAAUAUCCUCAUAC-5'(SEQ ID NO:4632)
KRAS-5305靶:5'-TAACTTTTAAATGTTTATAGGAGTATG-3'(SEQ ID NO:5118)
5'-CUUUUAAAUGUUUAUAGGAGUAUGU-3'(SEQ ID NO:6822)
3'-UUGAAAAUUUACAAAUAUCCUCAUACA-5'(SEQ ID NO:4633)
KRAS-5306靶:5'-AACTTTTAAATGTTTATAGGAGTATGT-3'(SEQ ID NO:5119)
5'-UUUUAAAUGUUUAUAGGAGUAUGUG-3'(SEQ ID NO:6823)
3'-UGAAAAUUUACAAAUAUCCUCAUACAC-5'(SEQ ID NO:4634)
KRAS-5307靶:5'-ACTTTTAAATGTTTATAGGAGTATGTG-3'(SEQ ID NO:5120)
5'-UUUAAAUGUUUAUAGGAGUAUGUGC-3'(SEQ ID NO:6824)
3'-GAAAAUUUACAAAUAUCCUCAUACACG-5'(SEQ ID NO:4635)
KRAS-5308靶:5'-CTTTTAAATGTTTATAGGAGTATGTGC-3'(SEQ ID NO:5121)
5'-UUAAAUGUUUAUAGGAGUAUGUGCU-3'(SEQ ID NO:6825)
3'-AAAAUUUACAAAUAUCCUCAUACACGA-5'(SEQ ID NO:4636)
KRAS-5309靶:5'-TTTTAAATGTTTATAGGAGTATGTGCT-3'(SEQ ID NO:5122)
5'-AAAUUUGUAAUAUUUUUGUCAUGAA-3'(SEQ ID NO:6826)
3'-AUUUUAAACAUUAUAAAAACAGUACUU-5'(SEQ ID NO:4637)
KRAS-5347靶:5'-TAAAATTTGTAATATTTTTGTCATGAA-3'(SEQ ID NO:5123)
5'-AAUUUGUAAUAUUUUUGUCAUGAAC-3'(SEQ ID NO:6827)
3'-UUUUAAACAUUAUAAAAACAGUACUUG-5'(SEQ ID NO:4638)
KRAS-5348靶:5'-AAAATTTGTAATATTTTTGTCATGAAC-3'(SEQ ID NO:5124)
5'-AUUUGUAAUAUUUUUGUCAUGAACU-3'(SEQ ID NO:6828)
3'-UUUAAACAUUAUAAAAACAGUACUUGA-5'(SEQ ID NO:4639)
KRAS-5349靶:5'-AAATTTGTAATATTTTTGTCATGAACT-3'(SEQ ID NO:5125)
5'-UUUGUAAUAUUUUUGUCAUGAACUG-3'(SEQ ID NO:6829)
3'-UUAAACAUUAUAAAAACAGUACUUGAC-5'(SEQ ID NO:4640)
KRAS-5350靶:5'-AATTTGTAATATTTTTGTCATGAACTG-3'(SEQ ID NO:5126)
5'-UUGUAAUAUUUUUGUCAUGAACUGU-3'(SEQ ID NO:6830)
3'-UAAACAUUAUAAAAACAGUACUUGACA-5'(SEQ ID NO:4641)
KRAS-5351靶:5'-ATTTGTAATATTTTTGTCATGAACTGT-3'(SEQ ID NO:5127)
5'-UGUAAUAUUUUUGUCAUGAACUGUA-3'(SEQ ID NO:6831)
3'-AAACAUUAUAAAAACAGUACUUGACAU-5'(SEQ ID NO:4642)
KRAS-5352靶:5'-TTTGTAATATTTTTGTCATGAACTGTA-3'(SEQ ID NO:5128)
5'-GUAAUAUUUUUGUCAUGAACUGUAC-3'(SEQ ID NO:6832)
3'-AACAUUAUAAAAACAGUACUUGACAUG-5'(SEQ ID NO:4643)
KRAS-5353靶:5'-TTGTAATATTTTTGTCATGAACTGTAC-3'(SEQ ID NO:5129)
5'-UAAUAUUUUUGUCAUGAACUGUACU-3'(SEQ ID NO:6833)
3'-ACAUUAUAAAAACAGUACUUGACAUGA-5'(SEQ ID NO:4644)
KRAS-5354靶:5'-TGTAATATTTTTGTCATGAACTGTACT-3'(SEQ ID NO:5130)
5'-AUUGUAAUGUAAUAAAAAUAGUUAC-3'(SEQ ID NO:6834)
3'-AAUAACAUUACAUUAUUUUUAUCAAUG-5'(SEQ ID NO:4645)
KRAS-5389靶:5'-TTATTGTAATGTAATAAAAATAGTTAC-3'(SEQ ID NO:5131)
5'-UUGUAAUGUAAUAAAAAUAGUUACA-3'(SEQ ID NO:6835)
3'-AUAACAUUACAUUAUUUUUAUCAAUGU-5'(SEQ ID NO:4646)
KRAS-5390靶:5'-TATTGTAATGTAATAAAAATAGTTACA-3'(SEQ ID NO:5132)
5'-UGUAAUGUAAUAAAAAUAGUUACAG-3'(SEQ ID NO:6836)
3'-UAACAUUACAUUAUUUUUAUCAAUGUC-5'(SEQ ID NO:4647)
KRAS-5391靶:5'-ATTGTAATGTAATAAAAATAGTTACAG-3'(SEQ ID NO:5133)
5'-GUAAUGUAAUAAAAAUAGUUACAGU-3'(SEQ ID NO:6837)
3'-AACAUUACAUUAUUUUUAUCAAUGUCA-5'(SEQ ID NO:4648)
KRAS-5392靶:5'-TTGTAATGTAATAAAAATAGTTACAGT-3'(SEQ ID NO:5134)
5'-UAAUGUAAUAAAAAUAGUUACAGUG-3'(SEQ ID NO:6838)
3'-ACAUUACAUUAUUUUUAUCAAUGUCAC-5'(SEQ ID NO:4649)
KRAS-5393靶:5'-TGTAATGTAATAAAAATAGTTACAGTG-3'(SEQ ID NO:5135)
每一DsiRNA的预计的21mer靶序列显示于表7中。
表7DsiRNA靶序列(21mer)
KRAS-204靶:5'-TAGTTGGAGCTGGTGGCGTAG-3’(SEQ ID NO:6843)
KRAS-204*靶:5'-TAGTTGGAGCTGTTGGCGTAG-3’(SEQ ID NO:6844)
KRAS-341靶:5'-GATATTCTCGACACAGCAGGT-3’(SEQ ID NO:6845)
KRAS-341*靶:5'-GATATTCTCGACACAGCAGGT-3’(SEQ ID NO:6846)
KRAS-343靶:5'-TATTCTCGACACAGCAGGTCA-3’(SEQ ID NO:6847)
KRAS-343*靶:5'-TATTCTCGACACAGCAGGTCA-3’(SEQ ID NO:6848)
KRAS-355靶:5'-AGCAGGTCAAGAGGAGTACAG-3’(SEQ ID NO:6849)
KRAS-355*靶:5'-AGCAGGTCATGAGGAGTACAG-3’(SEQ ID NO:6850)
KRAS-361靶:5'-TCAAGAGGAGTACAGTGCAAT-3’(SEQ ID NO:6851)
KRAS-361*靶:5'-TCATGAGGAGTACAGTGCAAT-3’(SEQ ID NO:6852)
KRAS-371靶:5'-TACAGTGCAATGAGGGACCAG-3’(SEQ ID NO:6853)
KRAS-401靶:5'-ACTGGGGAGGGCTTTCTTTGT-3’(SEQ ID NO:6854)
KRAS-404靶:5'-GGGGAGGGCTTTCTTTGTGTA-3’(SEQ ID NO:6855)
KRAS-406靶:5'-GGAGGGCTTTCTTTGTGTATT-3’(SEQ ID NO:6856)
KRAS-410靶:5'-GGCTTTCTTTGTGTATTTGCC-3’(SEQ ID NO:6857)
KRAS-415靶:5'-TCTTTGTGTATTTGCCATAAA-3’(SEQ ID NO:6858)
KRAS-416靶:5'-CTTTGTGTATTTGCCATAAAT-3’(SEQ ID NO:6859)
KRAS-417靶:5'-TTTGTGTATTTGCCATAAATA-3’(SEQ ID NO:6860)
KRAS-418靶:5'-TTGTGTATTTGCCATAAATAA-3’(SEQ ID NO:6861)
KRAS-419靶:5'-TGTGTATTTGCCATAAATAAT-3’(SEQ ID NO:6862)
KRAS-420靶:5'-GTGTATTTGCCATAAATAATA-3’(SEQ ID NO:6863)
KRAS-429靶:5'-CCATAAATAATACTAAATCAT-3’(SEQ ID NO:6864)
KRAS-434靶:5'-AATAATACTAAATCATTTGAA-3’(SEQ ID NO:6865)
KRAS-438靶:5'-ATACTAAATCATTTGAAGATA-3’(SEQ ID NO:6866)
KRAS-440靶:5'-ACTAAATCATTTGAAGATATT-3’(SEQ ID NO:6867)
KRAS-445靶:5'-ATCATTTGAAGATATTCACCA-3’(SEQ ID NO:6868)
KRAS-450靶:5'-TTGAAGATATTCACCATTATA-3’(SEQ ID NO:6869)
KRAS-452靶:5'-GAAGATATTCACCATTATAGA-3’(SEQ ID NO:6870)
KRAS-508靶:5'-ACCTATGGTCCTAGTAGGAAA-3’(SEQ ID NO:6871)
KRAS-534靶:5'-GTGATTTGCCTTCTAGAACAG-3’(SEQ ID NO:6872)
KRAS-760靶:5'-TTGATGATGCCTTCTATACAT-3’(SEQ ID NO:6873)
KRAS-776靶:5'-TACATTAGTTCGAGAAATTCG-3’(SEQ ID NO:6874)
KRAS-786靶:5'-CGAGAAATTCGAAAACATAAA-3’(SEQ ID NO:6875)
KRAS-795靶:5'-CGAAAACATAAAGAAAAGATG-3’(SEQ ID NO:6876)
KRAS-800靶:5'-ACATAAAGAAAAGATGAGCAA-3’(SEQ ID NO:6877)
KRAS-800*靶:5'-ACATAAAGAAAAGATGAGCAA-3’(SEQ ID NO:6878)
KRAS-920靶:5'-TTTTGTACATTACACTAAATT-3’(SEQ ID NO:6879)
KRAS-935靶:5'-TAAATTATTAGCATTTGTTTT-3’(SEQ ID NO:6880)
KRAS-940靶:5'-TATTAGCATTTGTTTTAGCAT-3’(SEQ ID NO:6881)
KRAS-1032靶:5'-GAAGTTTTTTTTTCCTCTAAG-3’(SEQ ID NO:6882)
KRAS-1048靶:5'-CTAAGTGCCAGTATTCCCAGA-3’(SEQ ID NO:6883)
KRAS-1188靶:5'-TTGGTGTGAAACAAATTAATG-3’(SEQ ID NO:6884)
KRAS-1256靶:5'-GGATTAATTACTAATTTCAGT-3’(SEQ ID NO:6885)
KRAS-1634靶:5'-GCTATATTTACATGCTACTAA-3’(SEQ ID NO:6886)
KRAS-5134靶:5'-ATTTTAACTATTTTTGTATAG-3’(SEQ ID NO:6887)
KRAS-5208靶:5'-TGCAGTGTGATCCAGTTGTTT-3’(SEQ ID NO:6888)
KRAS-174靶:5'-TGCTGAAAATGACTGAATATA-3'(SEQ ID NO:6889)
KRAS-180靶:5'-AAATGACTGAATATAAACTTG-3'(SEQ ID NO:6890)
KRAS-184靶:5'-GACTGAATATAAACTTGTGGT-3'(SEQ ID NO:6891)
KRAS-246靶:5'-AGCTAATTCAGAATCATTTTG-3'(SEQ ID NO:6892)
KRAS-270靶:5'-ACGAATATGATCCAACAATAG-3'(SEQ ID NO:6893)
KRAS-306靶:5'-AGCAAGTAGTAATTGATGGAG-3'(SEQ ID NO:6894)
KRAS-406靶:5'-GGAGGGCTTTCTTTGTGTATT-3'(SEQ ID NO:6895)
KRAS-415靶:5'-TCTTTGTGTATTTGCCATAAA-3'(SEQ ID NO:6896)
KRAS-416靶:5'-CTTTGTGTATTTGCCATAAAT-3'(SEQ ID NO:6897)
KRAS-417靶:5'-TTTGTGTATTTGCCATAAATA-3'(SEQ ID NO:6898)
KRAS-418靶:5'-TTGTGTATTTGCCATAAATAA-3'(SEQ ID NO:6899)
KRAS-422靶:5'-GTATTTGCCATAAATAATACT-3'(SEQ ID NO:6900)
KRAS-423靶:5'-TATTTGCCATAAATAATACTA-3'(SEQ ID NO:6901)
KRAS-429靶:5'-CCATAAATAATACTAAATCAT-3'(SEQ ID NO:6902)
KRAS-430靶:5'-CATAAATAATACTAAATCATT-3'(SEQ ID NO:6903)
KRAS-432靶:5'-TAAATAATACTAAATCATTTG-3'(SEQ ID NO:6904)
KRAS-433靶:5'-AAATAATACTAAATCATTTGA-3'(SEQ ID NO:6905)
KRAS-434靶:5'-AATAATACTAAATCATTTGAA-3'(SEQ ID NO:6906)
KRAS-435靶:5'-ATAATACTAAATCATTTGAAG-3'(SEQ ID NO:6907)
KRAS-448靶:5'-ATTTGAAGATATTCACCATTA-3'(SEQ ID NO:6908)
KRAS-450靶:5'-TTGAAGATATTCACCATTATA-3'(SEQ ID NO:6909)
KRAS-451靶:5'-TGAAGATATTCACCATTATAG-3'(SEQ ID NO:6910)
KRAS-452靶:5'-GAAGATATTCACCATTATAGA-3'(SEQ ID NO:6911)
KRAS-453靶:5'-AAGATATTCACCATTATAGAG-3'(SEQ ID NO:6912)
KRAS-463靶:5'-CCATTATAGAGAACAAATTAA-3'(SEQ ID NO:6913)
KRAS-465靶:5'-ATTATAGAGAACAAATTAAAA-3'(SEQ ID NO:6914)
KRAS-466靶:5'-TTATAGAGAACAAATTAAAAG-3'(SEQ ID NO:6915)
KRAS-467靶:5'-TATAGAGAACAAATTAAAAGA-3'(SEQ ID NO:6916)
KRAS-468靶:5'-ATAGAGAACAAATTAAAAGAG-3'(SEQ ID NO:6917)
KRAS-518靶:5'-CTAGTAGGAAATAAATGTGAT-3'(SEQ ID NO:6918)
KRAS-519靶:5'-TAGTAGGAAATAAATGTGATT-3'(SEQ ID NO:6919)
KRAS-583靶:5'-AAGAAGTTATGGAATTCCTTT-3'(SEQ ID NO:6920)
KRAS-586靶:5'-AAGTTATGGAATTCCTTTTAT-3'(SEQ ID NO:6921)
KRAS-587靶:5'-AGTTATGGAATTCCTTTTATT-3'(SEQ ID NO:6922)
KRAS-588靶:5'-GTTATGGAATTCCTTTTATTG-3'(SEQ ID NO:6923)
KRAS-589靶:5'-TTATGGAATTCCTTTTATTGA-3'(SEQ ID NO:6924)
KRAS-636靶:5'-TGGAGGATGCTTTTTATACAT-3'(SEQ ID NO:6925)
KRAS-638靶:5'-GAGGATGCTTTTTATACATTG-3'(SEQ ID NO:6926)
KRAS-678靶:5'-ACAGATTGAAAAAAATCAGCA-3'(SEQ ID NO:6927)
KRAS-679靶:5'-CAGATTGAAAAAAATCAGCAA-3'(SEQ ID NO:6928)
KRAS-681靶:5'-GATTGAAAAAAATCAGCAAAG-3'(SEQ ID NO:6929)
KRAS-682靶:5'-ATTGAAAAAAATCAGCAAAGA-3'(SEQ ID NO:6930)
KRAS-683靶:5'-TTGAAAAAAATCAGCAAAGAA-3'(SEQ ID NO:6931)
KRAS-684靶:5'-TGAAAAAAATCAGCAAAGAAG-3'(SEQ ID NO:6932)
KRAS-712靶:5'-TCCTGGCTGTGTGAAAATTAA-3'(SEQ ID NO:6933)
KRAS-716靶:5'-GGCTGTGTGAAAATTAAAAAA-3'(SEQ ID NO:6934)
KRAS-720靶:5'-GTGTGAAAATTAAAAAATGCA-3'(SEQ ID NO:6935)
KRAS-721靶:5'-TGTGAAAATTAAAAAATGCAT-3'(SEQ ID NO:6936)
KRAS-722靶:5'-GTGAAAATTAAAAAATGCATT-3'(SEQ ID NO:6937)
KRAS-723靶:5'-TGAAAATTAAAAAATGCATTA-3'(SEQ ID NO:6938)
KRAS-725靶:5'-AAAATTAAAAAATGCATTATA-3'(SEQ ID NO:6939)
KRAS-726靶:5'-AAATTAAAAAATGCATTATAA-3'(SEQ ID NO:6940)
KRAS-727靶:5'-AATTAAAAAATGCATTATAAT-3'(SEQ ID NO:6941)
KRAS-728靶:5'-ATTAAAAAATGCATTATAATG-3'(SEQ ID NO:6942)
KRAS-730靶:5'-TAAAAAATGCATTATAATGTA-3'(SEQ ID NO:6943)
KRAS-737靶:5'-TGCATTATAATGTAATCTGGG-3'(SEQ ID NO:6944)
KRAS-784靶:5'-TTCGAGAAATTCGAAAACATA-3'(SEQ ID NO:6945)
KRAS-785靶:5'-TCGAGAAATTCGAAAACATAA-3'(SEQ ID NO:6946)
KRAS-786靶:5'-CGAGAAATTCGAAAACATAAA-3'(SEQ ID NO:6947)
KRAS-789靶:5'-GAAATTCGAAAACATAAAGAA-3'(SEQ ID NO:6948)
KRAS-794靶:5'-TCGAAAACATAAAGAAAAGAT-3'(SEQ ID NO:6949)
KRAS-795靶:5'-CGAAAACATAAAGAAAAGATG-3'(SEQ ID NO:6950)
KRAS-819靶:5'-AAAGATGGTAAAAAGAAGAAA-3'(SEQ ID NO:6951)
KRAS-820靶:5'-AAGATGGTAAAAAGAAGAAAA-3'(SEQ ID NO:6952)
KRAS-822靶:5'-GATGGTAAAAAGAAGAAAAAG-3'(SEQ ID NO:6953)
KRAS-823靶:5'-ATGGTAAAAAGAAGAAAAAGA-3'(SEQ ID NO:6954)
KRAS-828靶:5'-AAAAAGAAGAAAAAGAAGTCA-3'(SEQ ID NO:6955)
KRAS-829靶:5'-AAAAGAAGAAAAAGAAGTCAA-3'(SEQ ID NO:6956)
KRAS-830靶:5'-AAAGAAGAAAAAGAAGTCAAA-3'(SEQ ID NO:6957)
KRAS-846靶:5'-TCAAAGACAAAGTGTGTAATT-3'(SEQ ID NO:6958)
KRAS-847靶:5'-CAAAGACAAAGTGTGTAATTA-3'(SEQ ID NO:6959)
KRAS-851靶:5'-GACAAAGTGTGTAATTATGTA-3'(SEQ ID NO:6960)
KRAS-853靶:5'-CAAAGTGTGTAATTATGTAAA-3'(SEQ ID NO:6961)
KRAS-857靶:5'-GTGTGTAATTATGTAAATACA-3'(SEQ ID NO:6962)
KRAS-859靶:5'-GTGTAATTATGTAAATACAAT-3'(SEQ ID NO:6963)
KRAS-861靶:5'-GTAATTATGTAAATACAATTT-3'(SEQ ID NO:6964)
KRAS-862靶:5'-TAATTATGTAAATACAATTTG-3'(SEQ ID NO:6965)
KRAS-866靶:5'-TATGTAAATACAATTTGTACT-3'(SEQ ID NO:6966)
KRAS-867靶:5'-ATGTAAATACAATTTGTACTT-3'(SEQ ID NO:6967)
KRAS-868靶:5'-TGTAAATACAATTTGTACTTT-3'(SEQ ID NO:6968)
KRAS-869靶:5'-GTAAATACAATTTGTACTTTT-3'(SEQ ID NO:6969)
KRAS-875靶:5'-ACAATTTGTACTTTTTTCTTA-3'(SEQ ID NO:6970)
KRAS-876靶:5'-CAATTTGTACTTTTTTCTTAA-3'(SEQ ID NO:6971)
KRAS-901靶:5'-TACTAGTACAAGTGGTAATTT-3'(SEQ ID NO:6972)
KRAS-902靶:5'-ACTAGTACAAGTGGTAATTTT-3'(SEQ ID NO:6973)
KRAS-908靶:5'-ACAAGTGGTAATTTTTGTACA-3'(SEQ ID NO:6974)
KRAS-909靶:5'-CAAGTGGTAATTTTTGTACAT-3'(SEQ ID NO:6975)
KRAS-916靶:5'-TAATTTTTGTACATTACACTA-3'(SEQ ID NO:6976)
KRAS-917靶:5'-AATTTTTGTACATTACACTAA-3'(SEQ ID NO:6977)
KRAS-918靶:5'-ATTTTTGTACATTACACTAAA-3'(SEQ ID NO:6978)
KRAS-919靶:5'-TTTTTGTACATTACACTAAAT-3'(SEQ ID NO:6979)
KRAS-920靶:5'-TTTTGTACATTACACTAAATT-3'(SEQ ID NO:6980)
KRAS-932靶:5'-CACTAAATTATTAGCATTTGT-3'(SEQ ID NO:6981)
KRAS-934靶:5'-CTAAATTATTAGCATTTGTTT-3'(SEQ ID NO:6982)
KRAS-935靶:5'-TAAATTATTAGCATTTGTTTT-3'(SEQ ID NO:6983)
KRAS-940靶:5'-TATTAGCATTTGTTTTAGCAT-3'(SEQ ID NO:6984)
KRAS-946靶:5'-CATTTGTTTTAGCATTACCTA-3'(SEQ ID NO:6985)
KRAS-947靶:5'-ATTTGTTTTAGCATTACCTAA-3'(SEQ ID NO:6986)
KRAS-949靶:5'-TTGTTTTAGCATTACCTAATT-3'(SEQ ID NO:6987)
KRAS-950靶:5'-TGTTTTAGCATTACCTAATTT-3'(SEQ ID NO:6988)
KRAS-951靶:5'-GTTTTAGCATTACCTAATTTT-3'(SEQ ID NO:6989)
KRAS-952靶:5'-TTTTAGCATTACCTAATTTTT-3'(SEQ ID NO:6990)
KRAS-988靶:5'-GACTGTTAGCTTTTACCTTAA-3'(SEQ ID NO:6991)
KRAS-989靶:5'-ACTGTTAGCTTTTACCTTAAA-3'(SEQ ID NO:6992)
KRAS-995靶:5'-AGCTTTTACCTTAAATGCTTA-3'(SEQ ID NO:6993)
KRAS-996靶:5'-GCTTTTACCTTAAATGCTTAT-3'(SEQ ID NO:6994)
KRAS-997靶:5'-CTTTTACCTTAAATGCTTATT-3'(SEQ ID NO:6995)
KRAS-1003靶:5'-CCTTAAATGCTTATTTTAAAA-3'(SEQ ID NO:6996)
KRAS-1004靶:5'-CTTAAATGCTTATTTTAAAAT-3'(SEQ ID NO:6997)
KRAS-1010靶:5'-TGCTTATTTTAAAATGACAGT-3'(SEQ ID NO:6998)
KRAS-1012靶:5'-CTTATTTTAAAATGACAGTGG-3'(SEQ ID NO:6999)
KRAS-1029靶:5'-GTGGAAGTTTTTTTTTCCTCT-3'(SEQ ID NO:7000)
KRAS-1031靶:5'-GGAAGTTTTTTTTTCCTCTAA-3'(SEQ ID NO:7001)
KRAS-1032靶:5'-GAAGTTTTTTTTTCCTCTAAG-3'(SEQ ID NO:7002)
KRAS-1070靶:5'-TTTTGGTTTTTGAACTAGCAA-3'(SEQ ID NO:7003)
KRAS-1092靶:5'-GCCTGTGAAAAAGAAACTGAA-3'(SEQ ID NO:7004)
KRAS-1099靶:5'-AAAAAGAAACTGAATACCTAA-3'(SEQ ID NO:7005)
KRAS-1100靶:5'-AAAAGAAACTGAATACCTAAG-3'(SEQ ID NO:7006)
KRAS-1106靶:5'-AACTGAATACCTAAGATTTCT-3'(SEQ ID NO:7007)
KRAS-1147靶:5'-TGCAGTTGATTACTTCTTATT-3'(SEQ ID NO:7008)
KRAS-1148靶:5'-GCAGTTGATTACTTCTTATTT-3'(SEQ ID NO:7009)
KRAS-1152靶:5'-TTGATTACTTCTTATTTTTCT-3'(SEQ ID NO:7010)
KRAS-1160靶:5'-TTCTTATTTTTCTTACCAATT-3'(SEQ ID NO:7011)
KRAS-1161靶:5'-TCTTATTTTTCTTACCAATTG-3'(SEQ ID NO:7012)
KRAS-1162靶:5'-CTTATTTTTCTTACCAATTGT-3'(SEQ ID NO:7013)
KRAS-1185靶:5'-ATGTTGGTGTGAAACAAATTA-3'(SEQ ID NO:7014)
KRAS-1188靶:5'-TTGGTGTGAAACAAATTAATG-3'(SEQ ID NO:7015)
KRAS-1189靶:5'-TGGTGTGAAACAAATTAATGA-3'(SEQ ID NO:7016)
KRAS-1197靶:5'-AACAAATTAATGAAGCTTTTG-3'(SEQ ID NO:7017)
KRAS-1198靶:5'-ACAAATTAATGAAGCTTTTGA-3'(SEQ ID NO:7018)
KRAS-1230靶:5'-TCTGTGTTTTATCTAGTCACA-3'(SEQ ID NO:7019)
KRAS-1231靶:5'-CTGTGTTTTATCTAGTCACAT-3'(SEQ ID NO:7020)
KRAS-1234靶:5'-TGTTTTATCTAGTCACATAAA-3'(SEQ ID NO:7021)
KRAS-1235靶:5'-GTTTTATCTAGTCACATAAAT-3'(SEQ ID NO:7022)
KRAS-1240靶:5'-ATCTAGTCACATAAATGGATT-3'(SEQ ID NO:7023)
KRAS-1241靶:5'-TCTAGTCACATAAATGGATTA-3'(SEQ ID NO:7024)
KRAS-1249靶:5'-CATAAATGGATTAATTACTAA-3'(SEQ ID NO:7025)
KRAS-1250靶:5'-ATAAATGGATTAATTACTAAT-3'(SEQ ID NO:7026)
KRAS-1255靶:5'-TGGATTAATTACTAATTTCAG-3'(SEQ ID NO:7027)
KRAS-1257靶:5'-GATTAATTACTAATTTCAGTT-3'(SEQ ID NO:7028)
KRAS-1258靶:5'-ATTAATTACTAATTTCAGTTG-3'(SEQ ID NO:7029)
KRAS-1259靶:5'-TTAATTACTAATTTCAGTTGA-3'(SEQ ID NO:7030)
KRAS-1287靶:5'-TAATTGGTTTTTACTGAAACA-3'(SEQ ID NO:7031)
KRAS-1291靶:5'-TGGTTTTTACTGAAACATTGA-3'(SEQ ID NO:7032)
KRAS-1292靶:5'-GGTTTTTACTGAAACATTGAG-3'(SEQ ID NO:7033)
KRAS-1307靶:5'-ATTGAGGGAACACAAATTTAT-3'(SEQ ID NO:7034)
KRAS-1308靶:5'-TTGAGGGAACACAAATTTATG-3'(SEQ ID NO:7035)
KRAS-1381靶:5'-TGATGAATGTAAAGTTACACT-3'(SEQ ID NO:7036)
KRAS-1382靶:5'-GATGAATGTAAAGTTACACTG-3'(SEQ ID NO:7037)
KRAS-1454靶:5'-CCAAAATATTATATTTTTTCT-3'(SEQ ID NO:7038)
KRAS-1455靶:5'-CAAAATATTATATTTTTTCTA-3'(SEQ ID NO:7039)
KRAS-1456靶:5'-AAAATATTATATTTTTTCTAT-3'(SEQ ID NO:7040)
KRAS-1457靶:5'-AAATATTATATTTTTTCTATA-3'(SEQ ID NO:7041)
KRAS-1459靶:5'-ATATTATATTTTTTCTATAAA-3'(SEQ ID NO:7042)
KRAS-1460靶:5'-TATTATATTTTTTCTATAAAA-3'(SEQ ID NO:7043)
KRAS-1461靶:5'-ATTATATTTTTTCTATAAAAA-3'(SEQ ID NO:7044)
KRAS-1462靶:5'-TTATATTTTTTCTATAAAAAG-3'(SEQ ID NO:7045)
KRAS-1463靶:5'-TATATTTTTTCTATAAAAAGA-3'(SEQ ID NO:7046)
KRAS-1464靶:5'-ATATTTTTTCTATAAAAAGAA-3'(SEQ ID NO:7047)
KRAS-1465靶:5'-TATTTTTTCTATAAAAAGAAA-3'(SEQ ID NO:7048)
KRAS-1466靶:5'-ATTTTTTCTATAAAAAGAAAA-3'(SEQ ID NO:7049)
KRAS-1471靶:5'-TTCTATAAAAAGAAAAAAATG-3'(SEQ ID NO:7050)
KRAS-1472靶:5'-TCTATAAAAAGAAAAAAATGG-3'(SEQ ID NO:7051)
KRAS-1474靶:5'-TATAAAAAGAAAAAAATGGAA-3'(SEQ ID NO:7052)
KRAS-1475靶:5'-ATAAAAAGAAAAAAATGGAAA-3'(SEQ ID NO:7053)
KRAS-1476靶:5'-TAAAAAGAAAAAAATGGAAAA-3'(SEQ ID NO:7054)
KRAS-1477靶:5'-AAAAAGAAAAAAATGGAAAAA-3'(SEQ ID NO:7055)
KRAS-1478靶:5'-AAAAGAAAAAAATGGAAAAAA-3'(SEQ ID NO:7056)
KRAS-1479靶:5'-AAAGAAAAAAATGGAAAAAAA-3'(SEQ ID NO:7057)
KRAS-1480靶:5'-AAGAAAAAAATGGAAAAAAAT-3'(SEQ ID NO:7058)
KRAS-1484靶:5'-AAAAAATGGAAAAAAATTACA-3'(SEQ ID NO:7059)
KRAS-1485靶:5'-AAAAATGGAAAAAAATTACAA-3'(SEQ ID NO:7060)
KRAS-1490靶:5'-TGGAAAAAAATTACAAGGCAA-3'(SEQ ID NO:7061)
KRAS-1491靶:5'-GGAAAAAAATTACAAGGCAAT-3'(SEQ ID NO:7062)
KRAS-1492靶:5'-GAAAAAAATTACAAGGCAATG-3'(SEQ ID NO:7063)
KRAS-1527靶:5'-GCCATTTCCTTTTCACATTAG-3'(SEQ ID NO:7064)
KRAS-1533靶:5'-TCCTTTTCACATTAGATAAAT-3'(SEQ ID NO:7065)
KRAS-1540靶:5'-CACATTAGATAAATTACTATA-3'(SEQ ID NO:7066)
KRAS-1541靶:5'-ACATTAGATAAATTACTATAA-3'(SEQ ID NO:7067)
KRAS-1542靶:5'-CATTAGATAAATTACTATAAA-3'(SEQ ID NO:7068)
KRAS-1597靶:5'-AGTATGAAATGGGGATTATTA-3'(SEQ ID NO:7069)
KRAS-1606靶:5'-TGGGGATTATTATAGCAACCA-3'(SEQ ID NO:7070)
KRAS-1633靶:5'-GGCTATATTTACATGCTACTA-3'(SEQ ID NO:7071)
KRAS-1634靶:5'-GCTATATTTACATGCTACTAA-3'(SEQ ID NO:7072)
KRAS-1635靶:5'-CTATATTTACATGCTACTAAA-3'(SEQ ID NO:7073)
KRAS-1636靶:5'-TATATTTACATGCTACTAAAT-3'(SEQ ID NO:7074)
KRAS-1637靶:5'-ATATTTACATGCTACTAAATT-3'(SEQ ID NO:7075)
KRAS-1642靶:5'-TACATGCTACTAAATTTTTAT-3'(SEQ ID NO:7076)
KRAS-1649靶:5'-TACTAAATTTTTATAATAATT-3'(SEQ ID NO:7077)
KRAS-1650靶:5'-ACTAAATTTTTATAATAATTG-3'(SEQ ID NO:7078)
KRAS-1652靶:5'-TAAATTTTTATAATAATTGAA-3'(SEQ ID NO:7079)
KRAS-1653靶:5'-AAATTTTTATAATAATTGAAA-3'(SEQ ID NO:7080)
KRAS-1654靶:5'-AATTTTTATAATAATTGAAAA-3'(SEQ ID NO:7081)
KRAS-1655靶:5'-ATTTTTATAATAATTGAAAAG-3'(SEQ ID NO:7082)
KRAS-1656靶:5'-TTTTTATAATAATTGAAAAGA-3'(SEQ ID NO:7083)
KRAS-1657靶:5'-TTTTATAATAATTGAAAAGAT-3'(SEQ ID NO:7084)
KRAS-1658靶:5'-TTTATAATAATTGAAAAGATT-3'(SEQ ID NO:7085)
KRAS-1659靶:5'-TTATAATAATTGAAAAGATTT-3'(SEQ ID NO:7086)
KRAS-1660靶:5'-TATAATAATTGAAAAGATTTT-3'(SEQ ID NO:7087)
KRAS-1664靶:5'-ATAATTGAAAAGATTTTAACA-3'(SEQ ID NO:7088)
KRAS-1665靶:5'-TAATTGAAAAGATTTTAACAA-3'(SEQ ID NO:7089)
KRAS-1667靶:5'-ATTGAAAAGATTTTAACAAGT-3'(SEQ ID NO:7090)
KRAS-1668靶:5'-TTGAAAAGATTTTAACAAGTA-3'(SEQ ID NO:7091)
KRAS-1669靶:5'-TGAAAAGATTTTAACAAGTAT-3'(SEQ ID NO:7092)
KRAS-1670靶:5'-GAAAAGATTTTAACAAGTATA-3'(SEQ ID NO:7093)
KRAS-1671靶:5'-AAAAGATTTTAACAAGTATAA-3'(SEQ ID NO:7094)
KRAS-1672靶:5'-AAAGATTTTAACAAGTATAAA-3'(SEQ ID NO:7095)
KRAS-1673靶:5'-AAGATTTTAACAAGTATAAAA-3'(SEQ ID NO:7096)
KRAS-1674靶:5'-AGATTTTAACAAGTATAAAAA-3'(SEQ ID NO:7097)
KRAS-1675靶:5'-GATTTTAACAAGTATAAAAAA-3'(SEQ ID NO:7098)
KRAS-1682靶:5'-ACAAGTATAAAAAATTCTCAT-3'(SEQ ID NO:7099)
KRAS-1683靶:5'-CAAGTATAAAAAATTCTCATA-3'(SEQ ID NO:7100)
KRAS-1684靶:5'-AAGTATAAAAAATTCTCATAG-3'(SEQ ID NO:7101)
KRAS-1685靶:5'-AGTATAAAAAATTCTCATAGG-3'(SEQ ID NO:7102)
KRAS-1686靶:5'-GTATAAAAAATTCTCATAGGA-3'(SEQ ID NO:7103)
KRAS-1687靶:5'-TATAAAAAATTCTCATAGGAA-3'(SEQ ID NO:7104)
KRAS-1688靶:5'-ATAAAAAATTCTCATAGGAAT-3'(SEQ ID NO:7105)
KRAS-1689靶:5'-TAAAAAATTCTCATAGGAATT-3'(SEQ ID NO:7106)
KRAS-1691靶:5'-AAAAATTCTCATAGGAATTAA-3'(SEQ ID NO:7107)
KRAS-1692靶:5'-AAAATTCTCATAGGAATTAAA-3'(SEQ ID NO:7108)
KRAS-1736靶:5'-CTCTTTCATAGTATAACTTTA-3'(SEQ ID NO:7109)
KRAS-1741靶:5'-TCATAGTATAACTTTAAATCT-3'(SEQ ID NO:7110)
KRAS-1742靶:5'-CATAGTATAACTTTAAATCTT-3'(SEQ ID NO:7111)
KRAS-1753靶:5'-TTTAAATCTTTTCTTCAACTT-3'(SEQ ID NO:7112)
KRAS-1754靶:5'-TTAAATCTTTTCTTCAACTTG-3'(SEQ ID NO:7113)
KRAS-1769靶:5'-AACTTGAGTCTTTGAAGATAG-3'(SEQ ID NO:7114)
KRAS-1771靶:5'-CTTGAGTCTTTGAAGATAGTT-3'(SEQ ID NO:7115)
KRAS-1772靶:5'-TTGAGTCTTTGAAGATAGTTT-3'(SEQ ID NO:7116)
KRAS-1783靶:5'-AAGATAGTTTTAATTCTGCTT-3'(SEQ ID NO:7117)
KRAS-1784靶:5'-AGATAGTTTTAATTCTGCTTG-3'(SEQ ID NO:7118)
KRAS-1785靶:5'-GATAGTTTTAATTCTGCTTGT-3'(SEQ ID NO:7119)
KRAS-1799靶:5'-TGCTTGTGACATTAAAAGATT-3'(SEQ ID NO:7120)
KRAS-2047靶:5'-AGCATTGCTTTTGTTTCTTAA-3'(SEQ ID NO:7121)
KRAS-2048靶:5'-GCATTGCTTTTGTTTCTTAAG-3'(SEQ ID NO:7122)
KRAS-2054靶:5'-CTTTTGTTTCTTAAGAAAACA-3'(SEQ ID NO:7123)
KRAS-2061靶:5'-TTCTTAAGAAAACAAACTCTT-3'(SEQ ID NO:7124)
KRAS-2062靶:5'-TCTTAAGAAAACAAACTCTTT-3'(SEQ ID NO:7125)
KRAS-2063靶:5'-CTTAAGAAAACAAACTCTTTT-3'(SEQ ID NO:7126)
KRAS-2064靶:5'-TTAAGAAAACAAACTCTTTTT-3'(SEQ ID NO:7127)
KRAS-2065靶:5'-TAAGAAAACAAACTCTTTTTT-3'(SEQ ID NO:7128)
KRAS-2066靶:5'-AAGAAAACAAACTCTTTTTTA-3'(SEQ ID NO:7129)
KRAS-2067靶:5'-AGAAAACAAACTCTTTTTTAA-3'(SEQ ID NO:7130)
KRAS-2071靶:5'-AACAAACTCTTTTTTAAAAAT-3'(SEQ ID NO:7131)
KRAS-2077靶:5'-CTCTTTTTTAAAAATTACTTT-3'(SEQ ID NO:7132)
KRAS-2078靶:5'-TCTTTTTTAAAAATTACTTTT-3'(SEQ ID NO:7133)
KRAS-2079靶:5'-CTTTTTTAAAAATTACTTTTA-3'(SEQ ID NO:7134)
KRAS-2080靶:5'-TTTTTTAAAAATTACTTTTAA-3'(SEQ ID NO:7135)
KRAS-2081靶:5'-TTTTTAAAAATTACTTTTAAA-3'(SEQ ID NO:7136)
KRAS-2082靶:5'-TTTTAAAAATTACTTTTAAAT-3'(SEQ ID NO:7137)
KRAS-2083靶:5'-TTTAAAAATTACTTTTAAATA-3'(SEQ ID NO:7138)
KRAS-2084靶:5'-TTAAAAATTACTTTTAAATAT-3'(SEQ ID NO:7139)
KRAS-2085靶:5'-TAAAAATTACTTTTAAATATT-3'(SEQ ID NO:7140)
KRAS-2092靶:5'-TACTTTTAAATATTAACTCAA-3'(SEQ ID NO:7141)
KRAS-2093靶:5'-ACTTTTAAATATTAACTCAAA-3'(SEQ ID NO:7142)
KRAS-2095靶:5'-TTTTAAATATTAACTCAAAAG-3'(SEQ ID NO:7143)
KRAS-2097靶:5'-TTAAATATTAACTCAAAAGTT-3'(SEQ ID NO:7144)
KRAS-2098靶:5'-TAAATATTAACTCAAAAGTTG-3'(SEQ ID NO:7145)
KRAS-2099靶:5'-AAATATTAACTCAAAAGTTGA-3'(SEQ ID NO:7146)
KRAS-2100靶:5'-AATATTAACTCAAAAGTTGAG-3'(SEQ ID NO:7147)
KRAS-2134靶:5'-GGTGTGCCAAGACATTAATTT-3'(SEQ ID NO:7148)
KRAS-2139靶:5'-GCCAAGACATTAATTTTTTTT-3'(SEQ ID NO:7149)
KRAS-2140靶:5'-CCAAGACATTAATTTTTTTTT-3'(SEQ ID NO:7150)
KRAS-2146靶:5'-CATTAATTTTTTTTTTAAACA-3'(SEQ ID NO:7151)
KRAS-2147靶:5'-ATTAATTTTTTTTTTAAACAA-3'(SEQ ID NO:7152)
KRAS-2149靶:5'-TAATTTTTTTTTTAAACAATG-3'(SEQ ID NO:7153)
KRAS-2151靶:5'-ATTTTTTTTTTAAACAATGAA-3'(SEQ ID NO:7154)
KRAS-2152靶:5'-TTTTTTTTTTAAACAATGAAG-3'(SEQ ID NO:7155)
KRAS-2153靶:5'-TTTTTTTTTAAACAATGAAGT-3'(SEQ ID NO:7156)
KRAS-2154靶:5'-TTTTTTTTAAACAATGAAGTG-3'(SEQ ID NO:7157)
KRAS-2155靶:5'-TTTTTTTAAACAATGAAGTGA-3'(SEQ ID NO:7158)
KRAS-2157靶:5'-TTTTTAAACAATGAAGTGAAA-3'(SEQ ID NO:7159)
KRAS-2158靶:5'-TTTTAAACAATGAAGTGAAAA-3'(SEQ ID NO:7160)
KRAS-2159靶:5'-TTTAAACAATGAAGTGAAAAA-3'(SEQ ID NO:7161)
KRAS-2167靶:5'-ATGAAGTGAAAAAGTTTTACA-3'(SEQ ID NO:7162)
KRAS-2173靶:5'-TGAAAAAGTTTTACAATCTCT-3'(SEQ ID NO:7163)
KRAS-2174靶:5'-GAAAAAGTTTTACAATCTCTA-3'(SEQ ID NO:7164)
KRAS-2175靶:5'-AAAAAGTTTTACAATCTCTAG-3'(SEQ ID NO:7165)
KRAS-2216靶:5'-ACTGGTTAAATTAACATTGCA-3'(SEQ ID NO:7166)
KRAS-2217靶:5'-CTGGTTAAATTAACATTGCAT-3'(SEQ ID NO:7167)
KRAS-2218靶:5'-TGGTTAAATTAACATTGCATA-3'(SEQ ID NO:7168)
KRAS-2229靶:5'-ACATTGCATAAACACTTTTCA-3'(SEQ ID NO:7169)
KRAS-2247靶:5'-TCAAGTCTGATCCATATTTAA-3'(SEQ ID NO:7170)
KRAS-2257靶:5'-TCCATATTTAATAATGCTTTA-3'(SEQ ID NO:7171)
KRAS-2258靶:5'-CCATATTTAATAATGCTTTAA-3'(SEQ ID NO:7172)
KRAS-2259靶:5'-CATATTTAATAATGCTTTAAA-3'(SEQ ID NO:7173)
KRAS-2260靶:5'-ATATTTAATAATGCTTTAAAA-3'(SEQ ID NO:7174)
KRAS-2261靶:5'-TATTTAATAATGCTTTAAAAT-3'(SEQ ID NO:7175)
KRAS-2262靶:5'-ATTTAATAATGCTTTAAAATA-3'(SEQ ID NO:7176)
KRAS-2264靶:5'-TTAATAATGCTTTAAAATAAA-3'(SEQ ID NO:7177)
KRAS-2265靶:5'-TAATAATGCTTTAAAATAAAA-3'(SEQ ID NO:7178)
KRAS-2266靶:5'-AATAATGCTTTAAAATAAAAA-3'(SEQ ID NO:7179)
KRAS-2267靶:5'-ATAATGCTTTAAAATAAAAAT-3'(SEQ ID NO:7180)
KRAS-2274靶:5'-TTTAAAATAAAAATAAAAACA-3'(SEQ ID NO:7181)
KRAS-2280靶:5'-ATAAAAATAAAAACAATCCTT-3'(SEQ ID NO:7182)
KRAS-2281靶:5'-TAAAAATAAAAACAATCCTTT-3'(SEQ ID NO:7183)
KRAS-2282靶:5'-AAAAATAAAAACAATCCTTTT-3'(SEQ ID NO:7184)
KRAS-2283靶:5'-AAAATAAAAACAATCCTTTTG-3'(SEQ ID NO:7185)
KRAS-2284靶:5'-AAATAAAAACAATCCTTTTGA-3'(SEQ ID NO:7186)
KRAS-2285靶:5'-AATAAAAACAATCCTTTTGAT-3'(SEQ ID NO:7187)
KRAS-2286靶:5'-ATAAAAACAATCCTTTTGATA-3'(SEQ ID NO:7188)
KRAS-2287靶:5'-TAAAAACAATCCTTTTGATAA-3'(SEQ ID NO:7189)
KRAS-2291靶:5'-AACAATCCTTTTGATAAATTT-3'(SEQ ID NO:7190)
KRAS-2296靶:5'-TCCTTTTGATAAATTTAAAAT-3'(SEQ ID NO:7191)
KRAS-2297靶:5'-CCTTTTGATAAATTTAAAATG-3'(SEQ ID NO:7192)
KRAS-2298靶:5'-CTTTTGATAAATTTAAAATGT-3'(SEQ ID NO:7193)
KRAS-2302靶:5'-TGATAAATTTAAAATGTTACT-3'(SEQ ID NO:7194)
KRAS-2303靶:5'-GATAAATTTAAAATGTTACTT-3'(SEQ ID NO:7195)
KRAS-2304靶:5'-ATAAATTTAAAATGTTACTTA-3'(SEQ ID NO:7196)
KRAS-2305靶:5'-TAAATTTAAAATGTTACTTAT-3'(SEQ ID NO:7197)
KRAS-2306靶:5'-AAATTTAAAATGTTACTTATT-3'(SEQ ID NO:7198)
KRAS-2307靶:5'-AATTTAAAATGTTACTTATTT-3'(SEQ ID NO:7199)
KRAS-2309靶:5'-TTTAAAATGTTACTTATTTTA-3'(SEQ ID NO:7200)
KRAS-2310靶:5'-TTAAAATGTTACTTATTTTAA-3'(SEQ ID NO:7201)
KRAS-2311靶:5'-TAAAATGTTACTTATTTTAAA-3'(SEQ ID NO:7202)
KRAS-2312靶:5'-AAAATGTTACTTATTTTAAAA-3'(SEQ ID NO:7203)
KRAS-2313靶:5'-AAATGTTACTTATTTTAAAAT-3'(SEQ ID NO:7204)
KRAS-2315靶:5'-ATGTTACTTATTTTAAAATAA-3'(SEQ ID NO:7205)
KRAS-2320靶:5'-ACTTATTTTAAAATAAATGAA-3'(SEQ ID NO:7206)
KRAS-2322靶:5'-TTATTTTAAAATAAATGAAGT-3'(SEQ ID NO:7207)
KRAS-2323靶:5'-TATTTTAAAATAAATGAAGTG-3'(SEQ ID NO:7208)
KRAS-2326靶:5'-TTTAAAATAAATGAAGTGAGA-3'(SEQ ID NO:7209)
KRAS-2327靶:5'-TTAAAATAAATGAAGTGAGAT-3'(SEQ ID NO:7210)
KRAS-2447靶:5'-TCCATTTCTTCATGTTAAAAG-3'(SEQ ID NO:7211)
KRAS-2448靶:5'-CCATTTCTTCATGTTAAAAGA-3'(SEQ ID NO:7212)
KRAS-2475靶:5'-CTCAAACTCTTAGTTTTTTTT-3'(SEQ ID NO:7213)
KRAS-2485靶:5'-TAGTTTTTTTTTTTTACAACT-3'(SEQ ID NO:7214)
KRAS-2486靶:5'-AGTTTTTTTTTTTTACAACTA-3'(SEQ ID NO:7215)
KRAS-2487靶:5'-GTTTTTTTTTTTTACAACTAT-3'(SEQ ID NO:7216)
KRAS-2488靶:5'-TTTTTTTTTTTTACAACTATG-3'(SEQ ID NO:7217)
KRAS-2489靶:5'-TTTTTTTTTTTACAACTATGT-3'(SEQ ID NO:7218)
KRAS-2490靶:5'-TTTTTTTTTTACAACTATGTA-3'(SEQ ID NO:7219)
KRAS-2491靶:5'-TTTTTTTTTACAACTATGTAA-3'(SEQ ID NO:7220)
KRAS-2492靶:5'-TTTTTTTTACAACTATGTAAT-3'(SEQ ID NO:7221)
KRAS-2493靶:5'-TTTTTTTACAACTATGTAATT-3'(SEQ ID NO:7222)
KRAS-2494靶:5'-TTTTTTACAACTATGTAATTT-3'(SEQ ID NO:7223)
KRAS-2495靶:5'-TTTTTACAACTATGTAATTTA-3'(SEQ ID NO:7224)
KRAS-2502靶:5'-AACTATGTAATTTATATTCCA-3'(SEQ ID NO:7225)
KRAS-2503靶:5'-ACTATGTAATTTATATTCCAT-3'(SEQ ID NO:7226)
KRAS-2504靶:5'-CTATGTAATTTATATTCCATT-3'(SEQ ID NO:7227)
KRAS-2510靶:5'-AATTTATATTCCATTTACATA-3'(SEQ ID NO:7228)
KRAS-2511靶:5'-ATTTATATTCCATTTACATAA-3'(SEQ ID NO:7229)
KRAS-2512靶:5'-TTTATATTCCATTTACATAAG-3'(SEQ ID NO:7230)
KRAS-2513靶:5'-TTATATTCCATTTACATAAGG-3'(SEQ ID NO:7231)
KRAS-2525靶:5'-TACATAAGGATACACTTATTT-3'(SEQ ID NO:7232)
KRAS-2529靶:5'-TAAGGATACACTTATTTGTCA-3'(SEQ ID NO:7233)
KRAS-2561靶:5'-ATCTGTAAATTTTTAACCTAT-3'(SEQ ID NO:7234)
KRAS-2562靶:5'-TCTGTAAATTTTTAACCTATG-3'(SEQ ID NO:7235)
KRAS-2563靶:5'-CTGTAAATTTTTAACCTATGT-3'(SEQ ID NO:7236)
KRAS-2619靶:5'-TGCAAGAGGTGAAGTTTATAT-3'(SEQ ID NO:7237)
KRAS-2621靶:5'-CAAGAGGTGAAGTTTATATTT-3'(SEQ ID NO:7238)
KRAS-2622靶:5'-AAGAGGTGAAGTTTATATTTG-3'(SEQ ID NO:7239)
KRAS-2624靶:5'-GAGGTGAAGTTTATATTTGAA-3'(SEQ ID NO:7240)
KRAS-2625靶:5'-AGGTGAAGTTTATATTTGAAT-3'(SEQ ID NO:7241)
KRAS-2630靶:5'-AAGTTTATATTTGAATATCCA-3'(SEQ ID NO:7242)
KRAS-2718靶:5'-ACTTGATGCAGTTTTAATACT-3'(SEQ ID NO:7243)
KRAS-2720靶:5'-TTGATGCAGTTTTAATACTTG-3'(SEQ ID NO:7244)
KRAS-2871靶:5'-GATTTGACCTAATCACTAATT-3'(SEQ ID NO:7245)
KRAS-2877靶:5'-ACCTAATCACTAATTTTCAGG-3'(SEQ ID NO:7246)
KRAS-2946靶:5'-CAGTAGGATTTTTCAAACCTG-3'(SEQ ID NO:7247)
KRAS-2991靶:5'-AGTGGAAGGAGAATTTAATAA-3'(SEQ ID NO:7248)
KRAS-2994靶:5'-GGAAGGAGAATTTAATAAAGA-3'(SEQ ID NO:7249)
KRAS-2996靶:5'-AAGGAGAATTTAATAAAGATA-3'(SEQ ID NO:7250)
KRAS-2997靶:5'-AGGAGAATTTAATAAAGATAG-3'(SEQ ID NO:7251)
KRAS-3001靶:5'-GAATTTAATAAAGATAGTGCT-3'(SEQ ID NO:7252)
KRAS-3030靶:5'-TCCTTAGGTAATCTATAACTA-3'(SEQ ID NO:7253)
KRAS-3031靶:5'-CCTTAGGTAATCTATAACTAG-3'(SEQ ID NO:7254)
KRAS-3065靶:5'-AACAGTAATACATTCCATTGT-3'(SEQ ID NO:7255)
KRAS-3067靶:5'-CAGTAATACATTCCATTGTTT-3'(SEQ ID NO:7256)
KRAS-3068靶:5'-AGTAATACATTCCATTGTTTT-3'(SEQ ID NO:7257)
KRAS-3069靶:5'-GTAATACATTCCATTGTTTTA-3'(SEQ ID NO:7258)
KRAS-3079靶:5'-CCATTGTTTTAGTAACCAGAA-3'(SEQ ID NO:7259)
KRAS-3093靶:5'-ACCAGAAATCTTCATGCAATG-3'(SEQ ID NO:7260)
KRAS-3103靶:5'-TTCATGCAATGAAAAATACTT-3'(SEQ ID NO:7261)
KRAS-3110靶:5'-AATGAAAAATACTTTAATTCA-3'(SEQ ID NO:7262)
KRAS-3112靶:5'-TGAAAAATACTTTAATTCATG-3'(SEQ ID NO:7263)
KRAS-3113靶:5'-GAAAAATACTTTAATTCATGA-3'(SEQ ID NO:7264)
KRAS-3127靶:5'-TTCATGAAGCTTACTTTTTTT-3'(SEQ ID NO:7265)
KRAS-3130靶:5'-ATGAAGCTTACTTTTTTTTTT-3'(SEQ ID NO:7266)
KRAS-3134靶:5'-AGCTTACTTTTTTTTTTTGGT-3'(SEQ ID NO:7267)
KRAS-3138靶:5'-TACTTTTTTTTTTTGGTGTCA-3'(SEQ ID NO:7268)
KRAS-3139靶:5'-ACTTTTTTTTTTTGGTGTCAG-3'(SEQ ID NO:7269)
KRAS-3297靶:5'-AACTAATTTTTGTATTTTTAG-3'(SEQ ID NO:7270)
KRAS-3300靶:5'-TAATTTTTGTATTTTTAGGAG-3'(SEQ ID NO:7271)
KRAS-3413靶:5'-CTCATTTATTCAGCAAATATT-3'(SEQ ID NO:7272)
KRAS-3415靶:5'-CATTTATTCAGCAAATATTTA-3'(SEQ ID NO:7273)
KRAS-3417靶:5'-TTTATTCAGCAAATATTTATT-3'(SEQ ID NO:7274)
KRAS-3589靶:5'-TATTTTAGTTTTGCAAAGAAG-3'(SEQ ID NO:7275)
KRAS-3630靶:5'-CTCTATAATTGTTTTGCTACG-3'(SEQ ID NO:7276)
KRAS-3677靶:5'-TACTTTATGTAAATCACTTCA-3'(SEQ ID NO:7277)
KRAS-3678靶:5'-ACTTTATGTAAATCACTTCAT-3'(SEQ ID NO:7278)
KRAS-3679靶:5'-CTTTATGTAAATCACTTCATT-3'(SEQ ID NO:7279)
KRAS-3680靶:5'-TTTATGTAAATCACTTCATTG-3'(SEQ ID NO:7280)
KRAS-3681靶:5'-TTATGTAAATCACTTCATTGT-3'(SEQ ID NO:7281)
KRAS-3682靶:5'-TATGTAAATCACTTCATTGTT-3'(SEQ ID NO:7282)
KRAS-3683靶:5'-ATGTAAATCACTTCATTGTTT-3'(SEQ ID NO:7283)
KRAS-3697靶:5'-ATTGTTTTAAAGGAATAAACT-3'(SEQ ID NO:7284)
KRAS-3698靶:5'-TTGTTTTAAAGGAATAAACTT-3'(SEQ ID NO:7285)
KRAS-3701靶:5'-TTTTAAAGGAATAAACTTGAT-3'(SEQ ID NO:7286)
KRAS-3702靶:5'-TTTAAAGGAATAAACTTGATT-3'(SEQ ID NO:7287)
KRAS-3703靶:5'-TTAAAGGAATAAACTTGATTA-3'(SEQ ID NO:7288)
KRAS-3705靶:5'-AAAGGAATAAACTTGATTATA-3'(SEQ ID NO:7289)
KRAS-3706靶:5'-AAGGAATAAACTTGATTATAT-3'(SEQ ID NO:7290)
KRAS-3707靶:5'-AGGAATAAACTTGATTATATT-3'(SEQ ID NO:7291)
KRAS-3708靶:5'-GGAATAAACTTGATTATATTG-3'(SEQ ID NO:7292)
KRAS-3709靶:5'-GAATAAACTTGATTATATTGT-3'(SEQ ID NO:7293)
KRAS-3714靶:5'-AACTTGATTATATTGTTTTTT-3'(SEQ ID NO:7294)
KRAS-3715靶:5'-ACTTGATTATATTGTTTTTTT-3'(SEQ ID NO:7295)
KRAS-3718靶:5'-TGATTATATTGTTTTTTTATT-3'(SEQ ID NO:7296)
KRAS-3723靶:5'-ATATTGTTTTTTTATTTGGCA-3'(SEQ ID NO:7297)
KRAS-3724靶:5'-TATTGTTTTTTTATTTGGCAT-3'(SEQ ID NO:7298)
KRAS-3728靶:5'-GTTTTTTTATTTGGCATAACT-3'(SEQ ID NO:7299)
KRAS-3729靶:5'-TTTTTTTATTTGGCATAACTG-3'(SEQ ID NO:7300)
KRAS-3741靶:5'-GCATAACTGTGATTCTTTTAG-3'(SEQ ID NO:7301)
KRAS-3746靶:5'-ACTGTGATTCTTTTAGGACAA-3'(SEQ ID NO:7302)
KRAS-3747靶:5'-CTGTGATTCTTTTAGGACAAT-3'(SEQ ID NO:7303)
KRAS-3783靶:5'-GGTGTATGTCAGATATTCATA-3'(SEQ ID NO:7304)
KRAS-3784靶:5'-GTGTATGTCAGATATTCATAT-3'(SEQ ID NO:7305)
KRAS-3810靶:5'-CAAATGTGTAATATTCCAGTT-3'(SEQ ID NO:7306)
KRAS-3838靶:5'-CATAAGTAATTAAAATATACT-3'(SEQ ID NO:7307)
KRAS-3839靶:5'-ATAAGTAATTAAAATATACTT-3'(SEQ ID NO:7308)
KRAS-3840靶:5'-TAAGTAATTAAAATATACTTA-3'(SEQ ID NO:7309)
KRAS-3841靶:5'-AAGTAATTAAAATATACTTAA-3'(SEQ ID NO:7310)
KRAS-3842靶:5'-AGTAATTAAAATATACTTAAA-3'(SEQ ID NO:7311)
KRAS-3843靶:5'-GTAATTAAAATATACTTAAAA-3'(SEQ ID NO:7312)
KRAS-3844靶:5'-TAATTAAAATATACTTAAAAA-3'(SEQ ID NO:7313)
KRAS-3845靶:5'-AATTAAAATATACTTAAAAAT-3'(SEQ ID NO:7314)
KRAS-3846靶:5'-ATTAAAATATACTTAAAAATT-3'(SEQ ID NO:7315)
KRAS-3848靶:5'-TAAAATATACTTAAAAATTAA-3'(SEQ ID NO:7316)
KRAS-3849靶:5'-AAAATATACTTAAAAATTAAT-3'(SEQ ID NO:7317)
KRAS-3850靶:5'-AAATATACTTAAAAATTAATA-3'(SEQ ID NO:7318)
KRAS-3851靶:5'-AATATACTTAAAAATTAATAG-3'(SEQ ID NO:7319)
KRAS-3855靶:5'-TACTTAAAAATTAATAGTTTT-3'(SEQ ID NO:7320)
KRAS-3859靶:5'-TAAAAATTAATAGTTTTATCT-3'(SEQ ID NO:7321)
KRAS-3860靶:5'-AAAAATTAATAGTTTTATCTG-3'(SEQ ID NO:7322)
KRAS-3861靶:5'-AAAATTAATAGTTTTATCTGG-3'(SEQ ID NO:7323)
KRAS-3876靶:5'-ATCTGGGTACAAATAAACAGG-3'(SEQ ID NO:7324)
KRAS-3915靶:5'-GACAAGGAAACTTCTATGTAA-3'(SEQ ID NO:7325)
KRAS-3916靶:5'-ACAAGGAAACTTCTATGTAAA-3'(SEQ ID NO:7326)
KRAS-3917靶:5'-CAAGGAAACTTCTATGTAAAA-3'(SEQ ID NO:7327)
KRAS-3926靶:5'-TTCTATGTAAAAATCACTATG-3'(SEQ ID NO:7328)
KRAS-3927靶:5'-TCTATGTAAAAATCACTATGA-3'(SEQ ID NO:7329)
KRAS-3928靶:5'-CTATGTAAAAATCACTATGAT-3'(SEQ ID NO:7330)
KRAS-3932靶:5'-GTAAAAATCACTATGATTTCT-3'(SEQ ID NO:7331)
KRAS-3933靶:5'-TAAAAATCACTATGATTTCTG-3'(SEQ ID NO:7332)
KRAS-3942靶:5'-CTATGATTTCTGAATTGCTAT-3'(SEQ ID NO:7333)
KRAS-3943靶:5'-TATGATTTCTGAATTGCTATG-3'(SEQ ID NO:7334)
KRAS-3960靶:5'-TATGTGAAACTACAGATCTTT-3'(SEQ ID NO:7335)
KRAS-3961靶:5'-ATGTGAAACTACAGATCTTTG-3'(SEQ ID NO:7336)
KRAS-3997靶:5'-AGGGTGTTAAGACTTACACAG-3'(SEQ ID NO:7337)
KRAS-4084靶:5'-TTTAGGCCTCTTGAATTTTTG-3'(SEQ ID NO:7338)
KRAS-4092靶:5'-TCTTGAATTTTTGATGTAGAT-3'(SEQ ID NO:7339)
KRAS-4093靶:5'-CTTGAATTTTTGATGTAGATG-3'(SEQ ID NO:7340)
KRAS-4108靶:5'-TAGATGGGCATTTTTTTAAGG-3'(SEQ ID NO:7341)
KRAS-4114靶:5'-GGCATTTTTTTAAGGTAGTGG-3'(SEQ ID NO:7342)
KRAS-4126靶:5'-AGGTAGTGGTTAATTACCTTT-3'(SEQ ID NO:7343)
KRAS-4128靶:5'-GTAGTGGTTAATTACCTTTAT-3'(SEQ ID NO:7344)
KRAS-4129靶:5'-TAGTGGTTAATTACCTTTATG-3'(SEQ ID NO:7345)
KRAS-4130靶:5'-AGTGGTTAATTACCTTTATGT-3'(SEQ ID NO:7346)
KRAS-4131靶:5'-GTGGTTAATTACCTTTATGTG-3'(SEQ ID NO:7347)
KRAS-4141靶:5'-ACCTTTATGTGAACTTTGAAT-3'(SEQ ID NO:7348)
KRAS-4146靶:5'-TATGTGAACTTTGAATGGTTT-3'(SEQ ID NO:7349)
KRAS-4152靶:5'-AACTTTGAATGGTTTAACAAA-3'(SEQ ID NO:7350)
KRAS-4156靶:5'-TTGAATGGTTTAACAAAAGAT-3'(SEQ ID NO:7351)
KRAS-4157靶:5'-TGAATGGTTTAACAAAAGATT-3'(SEQ ID NO:7352)
KRAS-4158靶:5'-GAATGGTTTAACAAAAGATTT-3'(SEQ ID NO:7353)
KRAS-4159靶:5'-AATGGTTTAACAAAAGATTTG-3'(SEQ ID NO:7354)
KRAS-4160靶:5'-ATGGTTTAACAAAAGATTTGT-3'(SEQ ID NO:7355)
KRAS-4162靶:5'-GGTTTAACAAAAGATTTGTTT-3'(SEQ ID NO:7356)
KRAS-4163靶:5'-GTTTAACAAAAGATTTGTTTT-3'(SEQ ID NO:7357)
KRAS-4167靶:5'-AACAAAAGATTTGTTTTTGTA-3'(SEQ ID NO:7358)
KRAS-4168靶:5'-ACAAAAGATTTGTTTTTGTAG-3'(SEQ ID NO:7359)
KRAS-4169靶:5'-CAAAAGATTTGTTTTTGTAGA-3'(SEQ ID NO:7360)
KRAS-4171靶:5'-AAAGATTTGTTTTTGTAGAGA-3'(SEQ ID NO:7361)
KRAS-4172靶:5'-AAGATTTGTTTTTGTAGAGAT-3'(SEQ ID NO:7362)
KRAS-4173靶:5'-AGATTTGTTTTTGTAGAGATT-3'(SEQ ID NO:7363)
KRAS-4174靶:5'-GATTTGTTTTTGTAGAGATTT-3'(SEQ ID NO:7364)
KRAS-4180靶:5'-TTTTTGTAGAGATTTTAAAGG-3'(SEQ ID NO:7365)
KRAS-4197靶:5'-AAGGGGGAGAATTCTAGAAAT-3'(SEQ ID NO:7366)
KRAS-4199靶:5'-GGGGGAGAATTCTAGAAATAA-3'(SEQ ID NO:7367)
KRAS-4200靶:5'-GGGGAGAATTCTAGAAATAAA-3'(SEQ ID NO:7368)
KRAS-4201靶:5'-GGGAGAATTCTAGAAATAAAT-3'(SEQ ID NO:7369)
KRAS-4202靶:5'-GGAGAATTCTAGAAATAAATG-3'(SEQ ID NO:7370)
KRAS-4203靶:5'-GAGAATTCTAGAAATAAATGT-3'(SEQ ID NO:7371)
KRAS-4208靶:5'-TTCTAGAAATAAATGTTACCT-3'(SEQ ID NO:7372)
KRAS-4209靶:5'-TCTAGAAATAAATGTTACCTA-3'(SEQ ID NO:7373)
KRAS-4210靶:5'-CTAGAAATAAATGTTACCTAA-3'(SEQ ID NO:7374)
KRAS-4211靶:5'-TAGAAATAAATGTTACCTAAT-3'(SEQ ID NO:7375)
KRAS-4212靶:5'-AGAAATAAATGTTACCTAATT-3'(SEQ ID NO:7376)
KRAS-4214靶:5'-AAATAAATGTTACCTAATTAT-3'(SEQ ID NO:7377)
KRAS-4225靶:5'-ACCTAATTATTACAGCCTTAA-3'(SEQ ID NO:7378)
KRAS-4226靶:5'-CCTAATTATTACAGCCTTAAA-3'(SEQ ID NO:7379)
KRAS-4240靶:5'-CCTTAAAGACAAAAATCCTTG-3'(SEQ ID NO:7380)
KRAS-4243靶:5'-TAAAGACAAAAATCCTTGTTG-3'(SEQ ID NO:7381)
KRAS-4255靶:5'-TCCTTGTTGAAGTTTTTTTAA-3'(SEQ ID NO:7382)
KRAS-4256靶:5'-CCTTGTTGAAGTTTTTTTAAA-3'(SEQ ID NO:7383)
KRAS-4258靶:5'-TTGTTGAAGTTTTTTTAAAAA-3'(SEQ ID NO:7384)
KRAS-4259靶:5'-TGTTGAAGTTTTTTTAAAAAA-3'(SEQ ID NO:7385)
KRAS-4263靶:5'-GAAGTTTTTTTAAAAAAAGCT-3'(SEQ ID NO:7386)
KRAS-4264靶:5'-AAGTTTTTTTAAAAAAAGCTA-3'(SEQ ID NO:7387)
KRAS-4265靶:5'-AGTTTTTTTAAAAAAAGCTAA-3'(SEQ ID NO:7388)
KRAS-4266靶:5'-GTTTTTTTAAAAAAAGCTAAA-3'(SEQ ID NO:7389)
KRAS-4267靶:5'-TTTTTTTAAAAAAAGCTAAAT-3'(SEQ ID NO:7390)
KRAS-4271靶:5'-TTTAAAAAAAGCTAAATTACA-3'(SEQ ID NO:7391)
KRAS-4273靶:5'-TAAAAAAAGCTAAATTACATA-3'(SEQ ID NO:7392)
KRAS-4295靶:5'-ACTTAGGCATTAACATGTTTG-3'(SEQ ID NO:7393)
KRAS-4296靶:5'-CTTAGGCATTAACATGTTTGT-3'(SEQ ID NO:7394)
KRAS-4327靶:5'-AGCAGACGTATATTGTATCAT-3'(SEQ ID NO:7395)
KRAS-4331靶:5'-GACGTATATTGTATCATTTGA-3'(SEQ ID NO:7396)
KRAS-4333靶:5'-CGTATATTGTATCATTTGAGT-3'(SEQ ID NO:7397)
KRAS-4336靶:5'-ATATTGTATCATTTGAGTGAA-3'(SEQ ID NO:7398)
KRAS-4337靶:5'-TATTGTATCATTTGAGTGAAT-3'(SEQ ID NO:7399)
KRAS-4338靶:5'-ATTGTATCATTTGAGTGAATG-3'(SEQ ID NO:7400)
KRAS-4404靶:5'-ATAGGAATTTAGAACCTAACT-3'(SEQ ID NO:7401)
KRAS-4405靶:5'-TAGGAATTTAGAACCTAACTT-3'(SEQ ID NO:7402)
KRAS-4409靶:5'-AATTTAGAACCTAACTTTTAT-3'(SEQ ID NO:7403)
KRAS-4410靶:5'-ATTTAGAACCTAACTTTTATA-3'(SEQ ID NO:7404)
KRAS-4411靶:5'-TTTAGAACCTAACTTTTATAG-3'(SEQ ID NO:7405)
KRAS-4412靶:5'-TTAGAACCTAACTTTTATAGG-3'(SEQ ID NO:7406)
KRAS-4424靶:5'-TTTTATAGGTTATCAAAACTG-3'(SEQ ID NO:7407)
KRAS-4426靶:5'-TTATAGGTTATCAAAACTGTT-3'(SEQ ID NO:7408)
KRAS-4460靶:5'-AATTTTGTCCTAATATATACA-3'(SEQ ID NO:7409)
KRAS-4461靶:5'-ATTTTGTCCTAATATATACAT-3'(SEQ ID NO:7410)
KRAS-4462靶:5'-TTTTGTCCTAATATATACATA-3'(SEQ ID NO:7411)
KRAS-4468靶:5'-CCTAATATATACATAGAAACT-3'(SEQ ID NO:7412)
KRAS-4473靶:5'-TATATACATAGAAACTTTGTG-3'(SEQ ID NO:7413)
KRAS-4516靶:5'-CACAAGTTCATCTCATTTGTA-3'(SEQ ID NO:7414)
KRAS-4527靶:5'-CTCATTTGTATTCCATTGATT-3'(SEQ ID NO:7415)
KRAS-4528靶:5'-TCATTTGTATTCCATTGATTT-3'(SEQ ID NO:7416)
KRAS-4529靶:5'-CATTTGTATTCCATTGATTTT-3'(SEQ ID NO:7417)
KRAS-4530靶:5'-ATTTGTATTCCATTGATTTTT-3'(SEQ ID NO:7418)
KRAS-4531靶:5'-TTTGTATTCCATTGATTTTTT-3'(SEQ ID NO:7419)
KRAS-4532靶:5'-TTGTATTCCATTGATTTTTTT-3'(SEQ ID NO:7420)
KRAS-4533靶:5'-TGTATTCCATTGATTTTTTTT-3'(SEQ ID NO:7421)
KRAS-4540靶:5'-CATTGATTTTTTTTTTCTTCT-3'(SEQ ID NO:7422)
KRAS-4541靶:5'-ATTGATTTTTTTTTTCTTCTA-3'(SEQ ID NO:7423)
KRAS-4545靶:5'-ATTTTTTTTTTCTTCTAAACA-3'(SEQ ID NO:7424)
KRAS-4546靶:5'-TTTTTTTTTTCTTCTAAACAT-3'(SEQ ID NO:7425)
KRAS-4547靶:5'-TTTTTTTTTCTTCTAAACATT-3'(SEQ ID NO:7426)
KRAS-4548靶:5'-TTTTTTTTCTTCTAAACATTT-3'(SEQ ID NO:7427)
KRAS-4549靶:5'-TTTTTTTCTTCTAAACATTTT-3'(SEQ ID NO:7428)
KRAS-4562靶:5'-AACATTTTTTCTTCAAACAGT-3'(SEQ ID NO:7429)
KRAS-4563靶:5'-ACATTTTTTCTTCAAACAGTA-3'(SEQ ID NO:7430)
KRAS-4564靶:5'-CATTTTTTCTTCAAACAGTAT-3'(SEQ ID NO:7431)
KRAS-4565靶:5'-ATTTTTTCTTCAAACAGTATA-3'(SEQ ID NO:7432)
KRAS-4566靶:5'-TTTTTTCTTCAAACAGTATAT-3'(SEQ ID NO:7433)
KRAS-4573靶:5'-TTCAAACAGTATATAACTTTT-3'(SEQ ID NO:7434)
KRAS-4578靶:5'-ACAGTATATAACTTTTTTTAG-3'(SEQ ID NO:7435)
KRAS-4579靶:5'-CAGTATATAACTTTTTTTAGG-3'(SEQ ID NO:7436)
KRAS-4580靶:5'-AGTATATAACTTTTTTTAGGG-3'(SEQ ID NO:7437)
KRAS-4581靶:5'-GTATATAACTTTTTTTAGGGG-3'(SEQ ID NO:7438)
KRAS-4587靶:5'-AACTTTTTTTAGGGGATTTTT-3'(SEQ ID NO:7439)
KRAS-4588靶:5'-ACTTTTTTTAGGGGATTTTTT-3'(SEQ ID NO:7440)
KRAS-4599靶:5'-GGGATTTTTTTTTAGACAGCA-3'(SEQ ID NO:7441)
KRAS-4600靶:5'-GGATTTTTTTTTAGACAGCAA-3'(SEQ ID NO:7442)
KRAS-4601靶:5'-GATTTTTTTTTAGACAGCAAA-3'(SEQ ID NO:7443)
KRAS-4629靶:5'-TGAAGATTTCCATTTGTCAAA-3'(SEQ ID NO:7444)
KRAS-4630靶:5'-GAAGATTTCCATTTGTCAAAA-3'(SEQ ID NO:7445)
KRAS-4631靶:5'-AAGATTTCCATTTGTCAAAAA-3'(SEQ ID NO:7446)
KRAS-4632靶:5'-AGATTTCCATTTGTCAAAAAG-3'(SEQ ID NO:7447)
KRAS-4637靶:5'-TCCATTTGTCAAAAAGTAATG-3'(SEQ ID NO:7448)
KRAS-4638靶:5'-CCATTTGTCAAAAAGTAATGA-3'(SEQ ID NO:7449)
KRAS-4639靶:5'-CATTTGTCAAAAAGTAATGAT-3'(SEQ ID NO:7450)
KRAS-4644靶:5'-GTCAAAAAGTAATGATTTCTT-3'(SEQ ID NO:7451)
KRAS-4645靶:5'-TCAAAAAGTAATGATTTCTTG-3'(SEQ ID NO:7452)
KRAS-4646靶:5'-CAAAAAGTAATGATTTCTTGA-3'(SEQ ID NO:7453)
KRAS-4647靶:5'-AAAAAGTAATGATTTCTTGAT-3'(SEQ ID NO:7454)
KRAS-4649靶:5'-AAAGTAATGATTTCTTGATAA-3'(SEQ ID NO:7455)
KRAS-4651靶:5'-AGTAATGATTTCTTGATAATT-3'(SEQ ID NO:7456)
KRAS-4652靶:5'-GTAATGATTTCTTGATAATTG-3'(SEQ ID NO:7457)
KRAS-4654靶:5'-AATGATTTCTTGATAATTGTG-3'(SEQ ID NO:7458)
KRAS-4655靶:5'-ATGATTTCTTGATAATTGTGT-3'(SEQ ID NO:7459)
KRAS-4660靶:5'-TTCTTGATAATTGTGTAGTAA-3'(SEQ ID NO:7460)
KRAS-4661靶:5'-TCTTGATAATTGTGTAGTAAT-3'(SEQ ID NO:7461)
KRAS-4662靶:5'-CTTGATAATTGTGTAGTAATG-3'(SEQ ID NO:7462)
KRAS-4664靶:5'-TGATAATTGTGTAGTAATGTT-3'(SEQ ID NO:7463)
KRAS-4667靶:5'-TAATTGTGTAGTAATGTTTTT-3'(SEQ ID NO:7464)
KRAS-4669靶:5'-ATTGTGTAGTAATGTTTTTTA-3'(SEQ ID NO:7465)
KRAS-4670靶:5'-TTGTGTAGTAATGTTTTTTAG-3'(SEQ ID NO:7466)
KRAS-4704靶:5'-CCTTAAAGCTGAATTTATATT-3'(SEQ ID NO:7467)
KRAS-4706靶:5'-TTAAAGCTGAATTTATATTTA-3'(SEQ ID NO:7468)
KRAS-4715靶:5'-AATTTATATTTAGTAACTTCT-3'(SEQ ID NO:7469)
KRAS-4716靶:5'-ATTTATATTTAGTAACTTCTG-3'(SEQ ID NO:7470)
KRAS-4717靶:5'-TTTATATTTAGTAACTTCTGT-3'(SEQ ID NO:7471)
KRAS-4722靶:5'-ATTTAGTAACTTCTGTGTTAA-3'(SEQ ID NO:7472)
KRAS-4773靶:5'-ACTGAATAGCTGTCATAAAAT-3'(SEQ ID NO:7473)
KRAS-4774靶:5'-CTGAATAGCTGTCATAAAATG-3'(SEQ ID NO:7474)
KRAS-4788靶:5'-TAAAATGAAACTTTCTTTCTA-3'(SEQ ID NO:7475)
KRAS-4789靶:5'-AAAATGAAACTTTCTTTCTAA-3'(SEQ ID NO:7476)
KRAS-4790靶:5'-AAATGAAACTTTCTTTCTAAA-3'(SEQ ID NO:7477)
KRAS-4792靶:5'-ATGAAACTTTCTTTCTAAAGA-3'(SEQ ID NO:7478)
KRAS-4796靶:5'-AACTTTCTTTCTAAAGAAAGA-3'(SEQ ID NO:7479)
KRAS-4821靶:5'-CACATGAGTTCTTGAAGAATA-3'(SEQ ID NO:7480)
KRAS-4830靶:5'-TCTTGAAGAATAGTCATAACT-3'(SEQ ID NO:7481)
KRAS-4831靶:5'-CTTGAAGAATAGTCATAACTA-3'(SEQ ID NO:7482)
KRAS-4832靶:5'-TTGAAGAATAGTCATAACTAG-3'(SEQ ID NO:7483)
KRAS-4835靶:5'-AAGAATAGTCATAACTAGATT-3'(SEQ ID NO:7484)
KRAS-4836靶:5'-AGAATAGTCATAACTAGATTA-3'(SEQ ID NO:7485)
KRAS-4837靶:5'-GAATAGTCATAACTAGATTAA-3'(SEQ ID NO:7486)
KRAS-4838靶:5'-AATAGTCATAACTAGATTAAG-3'(SEQ ID NO:7487)
KRAS-4842靶:5'-GTCATAACTAGATTAAGATCT-3'(SEQ ID NO:7488)
KRAS-4848靶:5'-ACTAGATTAAGATCTGTGTTT-3'(SEQ ID NO:7489)
KRAS-4850靶:5'-TAGATTAAGATCTGTGTTTTA-3'(SEQ ID NO:7490)
KRAS-4851靶:5'-AGATTAAGATCTGTGTTTTAG-3'(SEQ ID NO:7491)
KRAS-4853靶:5'-ATTAAGATCTGTGTTTTAGTT-3'(SEQ ID NO:7492)
KRAS-4860靶:5'-TCTGTGTTTTAGTTTAATAGT-3'(SEQ ID NO:7493)
KRAS-4861靶:5'-CTGTGTTTTAGTTTAATAGTT-3'(SEQ ID NO:7494)
KRAS-4863靶:5'-GTGTTTTAGTTTAATAGTTTG-3'(SEQ ID NO:7495)
KRAS-4865靶:5'-GTTTTAGTTTAATAGTTTGAA-3'(SEQ ID NO:7496)
KRAS-4866靶:5'-TTTTAGTTTAATAGTTTGAAG-3'(SEQ ID NO:7497)
KRAS-4892靶:5'-GTTTGGGATAATGATAGGTAA-3'(SEQ ID NO:7498)
KRAS-4894靶:5'-TTGGGATAATGATAGGTAATT-3'(SEQ ID NO:7499)
KRAS-4897靶:5'-GGATAATGATAGGTAATTTAG-3'(SEQ ID NO:7500)
KRAS-4898靶:5'-GATAATGATAGGTAATTTAGA-3'(SEQ ID NO:7501)
KRAS-4901靶:5'-AATGATAGGTAATTTAGATGA-3'(SEQ ID NO:7502)
KRAS-4902靶:5'-ATGATAGGTAATTTAGATGAA-3'(SEQ ID NO:7503)
KRAS-4907靶:5'-AGGTAATTTAGATGAATTTAG-3'(SEQ ID NO:7504)
KRAS-4909靶:5'-GTAATTTAGATGAATTTAGGG-3'(SEQ ID NO:7505)
KRAS-4916靶:5'-AGATGAATTTAGGGGAAAAAA-3'(SEQ ID NO:7506)
KRAS-4917靶:5'-GATGAATTTAGGGGAAAAAAA-3'(SEQ ID NO:7507)
KRAS-4928靶:5'-GGGAAAAAAAAGTTATCTGCA-3'(SEQ ID NO:7508)
KRAS-4929靶:5'-GGAAAAAAAAGTTATCTGCAG-3'(SEQ ID NO:7509)
KRAS-4934靶:5'-AAAAAGTTATCTGCAGATATG-3'(SEQ ID NO:7510)
KRAS-5035靶:5'-GTCTTGTGTTTTCATGTTGAA-3'(SEQ ID NO:7511)
KRAS-5036靶:5'-TCTTGTGTTTTCATGTTGAAA-3'(SEQ ID NO:7512)
KRAS-5037靶:5'-CTTGTGTTTTCATGTTGAAAA-3'(SEQ ID NO:7513)
KRAS-5047靶:5'-CATGTTGAAAATACTTTTGCA-3'(SEQ ID NO:7514)
KRAS-5048靶:5'-ATGTTGAAAATACTTTTGCAT-3'(SEQ ID NO:7515)
KRAS-5049靶:5'-TGTTGAAAATACTTTTGCATT-3'(SEQ ID NO:7516)
KRAS-5050靶:5'-GTTGAAAATACTTTTGCATTT-3'(SEQ ID NO:7517)
KRAS-5060靶:5'-CTTTTGCATTTTTCCTTTGAG-3'(SEQ ID NO:7518)
KRAS-5077靶:5'-TGAGTGCCAATTTCTTACTAG-3'(SEQ ID NO:7519)
KRAS-5082靶:5'-GCCAATTTCTTACTAGTACTA-3'(SEQ ID NO:7520)
KRAS-5083靶:5'-CCAATTTCTTACTAGTACTAT-3'(SEQ ID NO:7521)
KRAS-5092靶:5'-TACTAGTACTATTTCTTAATG-3'(SEQ ID NO:7522)
KRAS-5093靶:5'-ACTAGTACTATTTCTTAATGT-3'(SEQ ID NO:7523)
KRAS-5098靶:5'-TACTATTTCTTAATGTAACAT-3'(SEQ ID NO:7524)
KRAS-5099靶:5'-ACTATTTCTTAATGTAACATG-3'(SEQ ID NO:7525)
KRAS-5100靶:5'-CTATTTCTTAATGTAACATGT-3'(SEQ ID NO:7526)
KRAS-5107靶:5'-TTAATGTAACATGTTTACCTG-3'(SEQ ID NO:7527)
KRAS-5124靶:5'-CCTGGAATGTATTTTAACTAT-3'(SEQ ID NO:7528)
KRAS-5126靶:5'-TGGAATGTATTTTAACTATTT-3'(SEQ ID NO:7529)
KRAS-5127靶:5'-GGAATGTATTTTAACTATTTT-3'(SEQ ID NO:7530)
KRAS-5128靶:5'-GAATGTATTTTAACTATTTTT-3'(SEQ ID NO:7531)
KRAS-5129靶:5'-AATGTATTTTAACTATTTTTG-3'(SEQ ID NO:7532)
KRAS-5131靶:5'-TGTATTTTAACTATTTTTGTA-3'(SEQ ID NO:7533)
KRAS-5133靶:5'-TATTTTAACTATTTTTGTATA-3'(SEQ ID NO:7534)
KRAS-5134靶:5'-ATTTTAACTATTTTTGTATAG-3'(SEQ ID NO:7535)
KRAS-5135靶:5'-TTTTAACTATTTTTGTATAGT-3'(SEQ ID NO:7536)
KRAS-5142靶:5'-TATTTTTGTATAGTGTAAACT-3'(SEQ ID NO:7537)
KRAS-5143靶:5'-ATTTTTGTATAGTGTAAACTG-3'(SEQ ID NO:7538)
KRAS-5144靶:5'-TTTTTGTATAGTGTAAACTGA-3'(SEQ ID NO:7539)
KRAS-5159靶:5'-AACTGAAACATGCACATTTTG-3'(SEQ ID NO:7540)
KRAS-5165靶:5'-AACATGCACATTTTGTACATT-3'(SEQ ID NO:7541)
KRAS-5218靶:5'-TCCAGTTGTTTTCCATCATTT-3'(SEQ ID NO:7542)
KRAS-5220靶:5'-CAGTTGTTTTCCATCATTTGG-3'(SEQ ID NO:7543)
KRAS-5257靶:5'-ATGTTGGTCATATCAAACATT-3'(SEQ ID NO:7544)
KRAS-5258靶:5'-TGTTGGTCATATCAAACATTA-3'(SEQ ID NO:7545)
KRAS-5259靶:5'-GTTGGTCATATCAAACATTAA-3'(SEQ ID NO:7546)
KRAS-5263靶:5'-GTCATATCAAACATTAAAAAT-3'(SEQ ID NO:7547)
KRAS-5279靶:5'-AAAATGACCACTCTTTTAATT-3'(SEQ ID NO:7548)
KRAS-5280靶:5'-AAATGACCACTCTTTTAATTG-3'(SEQ ID NO:7549)
KRAS-5289靶:5'-CTCTTTTAATTGAAATTAACT-3'(SEQ ID NO:7550)
KRAS-5290靶:5'-TCTTTTAATTGAAATTAACTT-3'(SEQ ID NO:7551)
KRAS-5292靶:5'-TTTTAATTGAAATTAACTTTT-3'(SEQ ID NO:7552)
KRAS-5294靶:5'-TTAATTGAAATTAACTTTTAA-3'(SEQ ID NO:7553)
KRAS-5295靶:5'-TAATTGAAATTAACTTTTAAA-3'(SEQ ID NO:7554)
KRAS-5296靶:5'-AATTGAAATTAACTTTTAAAT-3'(SEQ ID NO:7555)
KRAS-5297靶:5'-ATTGAAATTAACTTTTAAATG-3'(SEQ ID NO:7556)
KRAS-5298靶:5'-TTGAAATTAACTTTTAAATGT-3'(SEQ ID NO:7557)
KRAS-5299靶:5'-TGAAATTAACTTTTAAATGTT-3'(SEQ ID NO:7558)
KRAS-5302靶:5'-AATTAACTTTTAAATGTTTAT-3'(SEQ ID NO:7559)
KRAS-5306靶:5'-AACTTTTAAATGTTTATAGGA-3'(SEQ ID NO:7560)
KRAS-5310靶:5'-TTTAAATGTTTATAGGAGTAT-3'(SEQ ID NO:7561)
KRAS-5311靶:5'-TTAAATGTTTATAGGAGTATG-3'(SEQ ID NO:7562)
KRAS-5333靶:5'-GCTGTGAAGTGATCTAAAATT-3'(SEQ ID NO:7563)
KRAS-5335靶:5'-TGTGAAGTGATCTAAAATTTG-3'(SEQ ID NO:7564)
KRAS-5336靶:5'-GTGAAGTGATCTAAAATTTGT-3'(SEQ ID NO:7565)
KRAS-5337靶:5'-TGAAGTGATCTAAAATTTGTA-3'(SEQ ID NO:7566)
KRAS-5338靶:5'-GAAGTGATCTAAAATTTGTAA-3'(SEQ ID NO:7567)
KRAS-5339靶:5'-AAGTGATCTAAAATTTGTAAT-3'(SEQ ID NO:7568)
KRAS-5340靶:5'-AGTGATCTAAAATTTGTAATA-3'(SEQ ID NO:7569)
KRAS-5344靶:5'-ATCTAAAATTTGTAATATTTT-3'(SEQ ID NO:7570)
KRAS-5345靶:5'-TCTAAAATTTGTAATATTTTT-3'(SEQ ID NO:7571)
KRAS-5349靶:5'-AAATTTGTAATATTTTTGTCA-3'(SEQ ID NO:7572)
KRAS-5350靶:5'-AATTTGTAATATTTTTGTCAT-3'(SEQ ID NO:7573)
KRAS-5351靶:5'-ATTTGTAATATTTTTGTCATG-3'(SEQ ID NO:7574)
KRAS-5355靶:5'-GTAATATTTTTGTCATGAACT-3'(SEQ ID NO:7575)
KRAS-5356靶:5'-TAATATTTTTGTCATGAACTG-3'(SEQ ID NO:7576)
KRAS-5372靶:5'-AACTGTACTACTCCTAATTAT-3'(SEQ ID NO:7577)
KRAS-5373靶:5'-ACTGTACTACTCCTAATTATT-3'(SEQ ID NO:7578)
KRAS-5383靶:5'-TCCTAATTATTGTAATGTAAT-3'(SEQ ID NO:7579)
KRAS-5384靶:5'-CCTAATTATTGTAATGTAATA-3'(SEQ ID NO:7580)
KRAS-5386靶:5'-TAATTATTGTAATGTAATAAA-3'(SEQ ID NO:7581)
KRAS-5388靶:5'-ATTATTGTAATGTAATAAAAA-3'(SEQ ID NO:7582)
KRAS-5389靶:5'-TTATTGTAATGTAATAAAAAT-3'(SEQ ID NO:7583)
KRAS-5391靶:5'-ATTGTAATGTAATAAAAATAG-3'(SEQ ID NO:7584)
KRAS-5392靶:5'-TTGTAATGTAATAAAAATAGT-3'(SEQ ID NO:7585)
KRAS-5396靶:5'-AATGTAATAAAAATAGTTACA-3'(SEQ ID NO:7586)
KRAS-5397靶:5'-ATGTAATAAAAATAGTTACAG-3'(SEQ ID NO:7587)
KRAS-5398靶:5'-TGTAATAAAAATAGTTACAGT-3'(SEQ ID NO:7588)
KRAS-5406靶:5'-AAATAGTTACAGTGACAAAAA-3'(SEQ ID NO:7589)
KRAS-5407靶:5'-AATAGTTACAGTGACAAAAAA-3'(SEQ ID NO:7590)
KRAS-5409靶:5'-TAGTTACAGTGACAAAAAAAA-3'(SEQ ID NO:7591)
KRAS-172靶:5'-CCTGCTGAAAATGACTGAATA-3'(SEQ ID NO:7592)
KRAS-178靶:5'-GAAAATGACTGAATATAAACT-3'(SEQ ID NO:7593)
KRAS-182靶:5'-ATGACTGAATATAAACTTGTG-3'(SEQ ID NO:7594)
KRAS-244靶:5'-ACAGCTAATTCAGAATCATTT-3'(SEQ ID NO:7595)
KRAS-268靶:5'-GGACGAATATGATCCAACAAT-3'(SEQ ID NO:7596)
KRAS-304靶:5'-GAAGCAAGTAGTAATTGATGG-3'(SEQ ID NO:7597)
KRAS-404靶:5'-GGGGAGGGCTTTCTTTGTGTA-3'(SEQ ID NO:7598)
KRAS-413靶:5'-TTTCTTTGTGTATTTGCCATA-3'(SEQ ID NO:7599)
KRAS-414靶:5'-TTCTTTGTGTATTTGCCATAA-3'(SEQ ID NO:7600)
KRAS-415靶:5'-TCTTTGTGTATTTGCCATAAA-3'(SEQ ID NO:7601)
KRAS-416靶:5'-CTTTGTGTATTTGCCATAAAT-3'(SEQ ID NO:7602)
KRAS-420靶:5'-GTGTATTTGCCATAAATAATA-3'(SEQ ID NO:7603)
KRAS-421靶:5'-TGTATTTGCCATAAATAATAC-3'(SEQ ID NO:7604)
KRAS-427靶:5'-TGCCATAAATAATACTAAATC-3'(SEQ ID NO:7605)
KRAS-428靶:5'-GCCATAAATAATACTAAATCA-3'(SEQ ID NO:7606)
KRAS-430靶:5'-CATAAATAATACTAAATCATT-3'(SEQ ID NO:7607)
KRAS-431靶:5'-ATAAATAATACTAAATCATTT-3'(SEQ ID NO:7608)
KRAS-432靶:5'-TAAATAATACTAAATCATTTG-3'(SEQ ID NO:7609)
KRAS-433靶:5'-AAATAATACTAAATCATTTGA-3'(SEQ ID NO:7610)
KRAS-446靶:5'-TCATTTGAAGATATTCACCAT-3'(SEQ ID NO:7611)
KRAS-448靶:5'-ATTTGAAGATATTCACCATTA-3'(SEQ ID NO:7612)
KRAS-449靶:5'-TTTGAAGATATTCACCATTAT-3'(SEQ ID NO:7613)
KRAS-450靶:5'-TTGAAGATATTCACCATTATA-3'(SEQ ID NO:7614)
KRAS-451靶:5'-TGAAGATATTCACCATTATAG-3'(SEQ ID NO:7615)
KRAS-461靶:5'-CACCATTATAGAGAACAAATT-3'(SEQ ID NO:7616)
KRAS-463靶:5'-CCATTATAGAGAACAAATTAA-3'(SEQ ID NO:7617)
KRAS-464靶:5'-CATTATAGAGAACAAATTAAA-3'(SEQ ID NO:7618)
KRAS-465靶:5'-ATTATAGAGAACAAATTAAAA-3'(SEQ ID NO:7619)
KRAS-466靶:5'-TTATAGAGAACAAATTAAAAG-3'(SEQ ID NO:7620)
KRAS-516靶:5'-TCCTAGTAGGAAATAAATGTG-3'(SEQ ID NO:7621)
KRAS-517靶:5'-CCTAGTAGGAAATAAATGTGA-3'(SEQ ID NO:7622)
KRAS-581靶:5'-GCAAGAAGTTATGGAATTCCT-3'(SEQ ID NO:7623)
KRAS-584靶:5'-AGAAGTTATGGAATTCCTTTT-3'(SEQ ID NO:7624)
KRAS-585靶:5'-GAAGTTATGGAATTCCTTTTA-3'(SEQ ID NO:7625)
KRAS-586靶:5'-AAGTTATGGAATTCCTTTTAT-3'(SEQ ID NO:7626)
KRAS-587靶:5'-AGTTATGGAATTCCTTTTATT-3'(SEQ ID NO:7627)
KRAS-634靶:5'-AGTGGAGGATGCTTTTTATAC-3'(SEQ ID NO:7628)
KRAS-636靶:5'-TGGAGGATGCTTTTTATACAT-3'(SEQ ID NO:7629)
KRAS-676靶:5'-ATACAGATTGAAAAAAATCAG-3'(SEQ ID NO:7630)
KRAS-677靶:5'-TACAGATTGAAAAAAATCAGC-3'(SEQ ID NO:7631)
KRAS-679靶:5'-CAGATTGAAAAAAATCAGCAA-3'(SEQ ID NO:7632)
KRAS-680靶:5'-AGATTGAAAAAAATCAGCAAA-3'(SEQ ID NO:7633)
KRAS-681靶:5'-GATTGAAAAAAATCAGCAAAG-3'(SEQ ID NO:7634)
KRAS-682靶:5'-ATTGAAAAAAATCAGCAAAGA-3'(SEQ ID NO:7635)
KRAS-710靶:5'-ACTCCTGGCTGTGTGAAAATT-3'(SEQ ID NO:7636)
KRAS-714靶:5'-CTGGCTGTGTGAAAATTAAAA-3'(SEQ ID NO:7637)
KRAS-718靶:5'-CTGTGTGAAAATTAAAAAATG-3'(SEQ ID NO:7638)
KRAS-719靶:5'-TGTGTGAAAATTAAAAAATGC-3'(SEQ ID NO:7639)
KRAS-720靶:5'-GTGTGAAAATTAAAAAATGCA-3'(SEQ ID NO:7640)
KRAS-721靶:5'-TGTGAAAATTAAAAAATGCAT-3'(SEQ ID NO:7641)
KRAS-723靶:5'-TGAAAATTAAAAAATGCATTA-3'(SEQ ID NO:7642)
KRAS-724靶:5'-GAAAATTAAAAAATGCATTAT-3'(SEQ ID NO:7643)
KRAS-725靶:5'-AAAATTAAAAAATGCATTATA-3'(SEQ ID NO:7644)
KRAS-726靶:5'-AAATTAAAAAATGCATTATAA-3'(SEQ ID NO:7645)
KRAS-728靶:5'-ATTAAAAAATGCATTATAATG-3'(SEQ ID NO:7646)
KRAS-735靶:5'-AATGCATTATAATGTAATCTG-3'(SEQ ID NO:7647)
KRAS-782靶:5'-AGTTCGAGAAATTCGAAAACA-3'(SEQ ID NO:7648)
KRAS-783靶:5'-GTTCGAGAAATTCGAAAACAT-3'(SEQ ID NO:7649)
KRAS-784靶:5'-TTCGAGAAATTCGAAAACATA-3'(SEQ ID NO:7650)
KRAS-787靶:5'-GAGAAATTCGAAAACATAAAG-3'(SEQ ID NO:7651)
KRAS-792靶:5'-ATTCGAAAACATAAAGAAAAG-3'(SEQ ID NO:7652)
KRAS-793靶:5'-TTCGAAAACATAAAGAAAAGA-3'(SEQ ID NO:7653)
KRAS-817靶:5'-GCAAAGATGGTAAAAAGAAGA-3'(SEQ ID NO:7654)
KRAS-818靶:5'-CAAAGATGGTAAAAAGAAGAA-3'(SEQ ID NO:7655)
KRAS-820靶:5'-AAGATGGTAAAAAGAAGAAAA-3'(SEQ ID NO:7656)
KRAS-821靶:5'-AGATGGTAAAAAGAAGAAAAA-3'(SEQ ID NO:7657)
KRAS-826靶:5'-GTAAAAAGAAGAAAAAGAAGT-3'(SEQ ID NO:7658)
KRAS-827靶:5'-TAAAAAGAAGAAAAAGAAGTC-3'(SEQ ID NO:7659)
KRAS-828靶:5'-AAAAAGAAGAAAAAGAAGTCA-3'(SEQ ID NO:7660)
KRAS-844靶:5'-AGTCAAAGACAAAGTGTGTAA-3'(SEQ ID NO:7661)
KRAS-845靶:5'-GTCAAAGACAAAGTGTGTAAT-3'(SEQ ID NO:7662)
KRAS-849靶:5'-AAGACAAAGTGTGTAATTATG-3'(SEQ ID NO:7663)
KRAS-851靶:5'-GACAAAGTGTGTAATTATGTA-3'(SEQ ID NO:7664)
KRAS-855靶:5'-AAGTGTGTAATTATGTAAATA-3'(SEQ ID NO:7665)
KRAS-857靶:5'-GTGTGTAATTATGTAAATACA-3'(SEQ ID NO:7666)
KRAS-859靶:5'-GTGTAATTATGTAAATACAAT-3'(SEQ ID NO:7667)
KRAS-860靶:5'-TGTAATTATGTAAATACAATT-3'(SEQ ID NO:7668)
KRAS-864靶:5'-ATTATGTAAATACAATTTGTA-3'(SEQ ID NO:7669)
KRAS-865靶:5'-TTATGTAAATACAATTTGTAC-3'(SEQ ID NO:7670)
KRAS-866靶:5'-TATGTAAATACAATTTGTACT-3'(SEQ ID NO:7671)
KRAS-867靶:5'-ATGTAAATACAATTTGTACTT-3'(SEQ ID NO:7672)
KRAS-873靶:5'-ATACAATTTGTACTTTTTTCT-3'(SEQ ID NO:7673)
KRAS-874靶:5'-TACAATTTGTACTTTTTTCTT-3'(SEQ ID NO:7674)
KRAS-899靶:5'-CATACTAGTACAAGTGGTAAT-3'(SEQ ID NO:7675)
KRAS-900靶:5'-ATACTAGTACAAGTGGTAATT-3'(SEQ ID NO:7676)
KRAS-906靶:5'-GTACAAGTGGTAATTTTTGTA-3'(SEQ ID NO:7677)
KRAS-907靶:5'-TACAAGTGGTAATTTTTGTAC-3'(SEQ ID NO:7678)
KRAS-914靶:5'-GGTAATTTTTGTACATTACAC-3'(SEQ ID NO:7679)
KRAS-915靶:5'-GTAATTTTTGTACATTACACT-3'(SEQ ID NO:7680)
KRAS-916靶:5'-TAATTTTTGTACATTACACTA-3'(SEQ ID NO:7681)
KRAS-917靶:5'-AATTTTTGTACATTACACTAA-3'(SEQ ID NO:7682)
KRAS-918靶:5'-ATTTTTGTACATTACACTAAA-3'(SEQ ID NO:7683)
KRAS-930靶:5'-TACACTAAATTATTAGCATTT-3'(SEQ ID NO:7684)
KRAS-932靶:5'-CACTAAATTATTAGCATTTGT-3'(SEQ ID NO:7685)
KRAS-933靶:5'-ACTAAATTATTAGCATTTGTT-3'(SEQ ID NO:7686)
KRAS-938靶:5'-ATTATTAGCATTTGTTTTAGC-3'(SEQ ID NO:7687)
KRAS-944靶:5'-AGCATTTGTTTTAGCATTACC-3'(SEQ ID NO:7688)
KRAS-945靶:5'-GCATTTGTTTTAGCATTACCT-3'(SEQ ID NO:7689)
KRAS-947靶:5'-ATTTGTTTTAGCATTACCTAA-3'(SEQ ID NO:7690)
KRAS-948靶:5'-TTTGTTTTAGCATTACCTAAT-3'(SEQ ID NO:7691)
KRAS-949靶:5'-TTGTTTTAGCATTACCTAATT-3'(SEQ ID NO:7692)
KRAS-950靶:5'-TGTTTTAGCATTACCTAATTT-3'(SEQ ID NO:7693)
KRAS-986靶:5'-CAGACTGTTAGCTTTTACCTT-3'(SEQ ID NO:7694)
KRAS-987靶:5'-AGACTGTTAGCTTTTACCTTA-3'(SEQ ID NO:7695)
KRAS-993靶:5'-TTAGCTTTTACCTTAAATGCT-3'(SEQ ID NO:7696)
KRAS-994靶:5'-TAGCTTTTACCTTAAATGCTT-3'(SEQ ID NO:7697)
KRAS-995靶:5'-AGCTTTTACCTTAAATGCTTA-3'(SEQ ID NO:7698)
KRAS-1001靶:5'-TACCTTAAATGCTTATTTTAA-3'(SEQ ID NO:7699)
KRAS-1002靶:5'-ACCTTAAATGCTTATTTTAAA-3'(SEQ ID NO:7700)
KRAS-1008靶:5'-AATGCTTATTTTAAAATGACA-3'(SEQ ID NO:7701)
KRAS-1010靶:5'-TGCTTATTTTAAAATGACAGT-3'(SEQ ID NO:7702)
KRAS-1027靶:5'-CAGTGGAAGTTTTTTTTTCCT-3'(SEQ ID NO:7703)
KRAS-1029靶:5'-GTGGAAGTTTTTTTTTCCTCT-3'(SEQ ID NO:7704)
KRAS-1030靶:5'-TGGAAGTTTTTTTTTCCTCTA-3'(SEQ ID NO:7705)
KRAS-1068靶:5'-AGTTTTGGTTTTTGAACTAGC-3'(SEQ ID NO:7706)
KRAS-1090靶:5'-ATGCCTGTGAAAAAGAAACTG-3'(SEQ ID NO:7707)
KRAS-1097靶:5'-TGAAAAAGAAACTGAATACCT-3'(SEQ ID NO:7708)
KRAS-1098靶:5'-GAAAAAGAAACTGAATACCTA-3'(SEQ ID NO:7709)
KRAS-1104靶:5'-GAAACTGAATACCTAAGATTT-3'(SEQ ID NO:7710)
KRAS-1145靶:5'-CATGCAGTTGATTACTTCTTA-3'(SEQ ID NO:7711)
KRAS-1146靶:5'-ATGCAGTTGATTACTTCTTAT-3'(SEQ ID NO:7712)
KRAS-1150靶:5'-AGTTGATTACTTCTTATTTTT-3'(SEQ ID NO:7713)
KRAS-1158靶:5'-ACTTCTTATTTTTCTTACCAA-3'(SEQ ID NO:7714)
KRAS-1159靶:5'-CTTCTTATTTTTCTTACCAAT-3'(SEQ ID NO:7715)
KRAS-1160靶:5'-TTCTTATTTTTCTTACCAATT-3'(SEQ ID NO:7716)
KRAS-1183靶:5'-GAATGTTGGTGTGAAACAAAT-3'(SEQ ID NO:7717)
KRAS-1186靶:5'-TGTTGGTGTGAAACAAATTAA-3'(SEQ ID NO:7718)
KRAS-1187靶:5'-GTTGGTGTGAAACAAATTAAT-3'(SEQ ID NO:7719)
KRAS-1195靶:5'-GAAACAAATTAATGAAGCTTT-3'(SEQ ID NO:7720)
KRAS-1196靶:5'-AAACAAATTAATGAAGCTTTT-3'(SEQ ID NO:7721)
KRAS-1228靶:5'-ATTCTGTGTTTTATCTAGTCA-3'(SEQ ID NO:7722)
KRAS-1229靶:5'-TTCTGTGTTTTATCTAGTCAC-3'(SEQ ID NO:7723)
KRAS-1232靶:5'-TGTGTTTTATCTAGTCACATA-3'(SEQ ID NO:7724)
KRAS-1233靶:5'-GTGTTTTATCTAGTCACATAA-3'(SEQ ID NO:7725)
KRAS-1238靶:5'-TTATCTAGTCACATAAATGGA-3'(SEQ ID NO:7726)
KRAS-1239靶:5'-TATCTAGTCACATAAATGGAT-3'(SEQ ID NO:7727)
KRAS-1247靶:5'-CACATAAATGGATTAATTACT-3'(SEQ ID NO:7728)
KRAS-1248靶:5'-ACATAAATGGATTAATTACTA-3'(SEQ ID NO:7729)
KRAS-1253靶:5'-AATGGATTAATTACTAATTTC-3'(SEQ ID NO:7730)
KRAS-1255靶:5'-TGGATTAATTACTAATTTCAG-3'(SEQ ID NO:7731)
KRAS-1256靶:5'-GGATTAATTACTAATTTCAGT-3'(SEQ ID NO:7732)
KRAS-1257靶:5'-GATTAATTACTAATTTCAGTT-3'(SEQ ID NO:7733)
KRAS-1285靶:5'-TCTAATTGGTTTTTACTGAAA-3'(SEQ ID NO:7734)
KRAS-1289靶:5'-ATTGGTTTTTACTGAAACATT-3'(SEQ ID NO:7735)
KRAS-1290靶:5'-TTGGTTTTTACTGAAACATTG-3'(SEQ ID NO:7736)
KRAS-1305靶:5'-ACATTGAGGGAACACAAATTT-3'(SEQ ID NO:7737)
KRAS-1306靶:5'-CATTGAGGGAACACAAATTTA-3'(SEQ ID NO:7738)
KRAS-1379靶:5'-CCTGATGAATGTAAAGTTACA-3'(SEQ ID NO:7739)
KRAS-1380靶:5'-CTGATGAATGTAAAGTTACAC-3'(SEQ ID NO:7740)
KRAS-1452靶:5'-CCCCAAAATATTATATTTTTT-3'(SEQ ID NO:7741)
KRAS-1453靶:5'-CCCAAAATATTATATTTTTTC-3'(SEQ ID NO:7742)
KRAS-1454靶:5'-CCAAAATATTATATTTTTTCT-3'(SEQ ID NO:7743)
KRAS-1455靶:5'-CAAAATATTATATTTTTTCTA-3'(SEQ ID NO:7744)
KRAS-1457靶:5'-AAATATTATATTTTTTCTATA-3'(SEQ ID NO:7745)
KRAS-1458靶:5'-AATATTATATTTTTTCTATAA-3'(SEQ ID NO:7746)
KRAS-1459靶:5'-ATATTATATTTTTTCTATAAA-3'(SEQ ID NO:7747)
KRAS-1460靶:5'-TATTATATTTTTTCTATAAAA-3'(SEQ ID NO:7748)
KRAS-1461靶:5'-ATTATATTTTTTCTATAAAAA-3'(SEQ ID NO:7749)
KRAS-1462靶:5'-TTATATTTTTTCTATAAAAAG-3'(SEQ ID NO:7750)
KRAS-1463靶:5'-TATATTTTTTCTATAAAAAGA-3'(SEQ ID NO:7751)
KRAS-1464靶:5'-ATATTTTTTCTATAAAAAGAA-3'(SEQ ID NO:7752)
KRAS-1469靶:5'-TTTTCTATAAAAAGAAAAAAA-3'(SEQ ID NO:7753)
KRAS-1470靶:5'-TTTCTATAAAAAGAAAAAAAT-3'(SEQ ID NO:7754)
KRAS-1472靶:5'-TCTATAAAAAGAAAAAAATGG-3'(SEQ ID NO:7755)
KRAS-1473靶:5'-CTATAAAAAGAAAAAAATGGA-3'(SEQ ID NO:7756)
KRAS-1474靶:5'-TATAAAAAGAAAAAAATGGAA-3'(SEQ ID NO:7757)
KRAS-1475靶:5'-ATAAAAAGAAAAAAATGGAAA-3'(SEQ ID NO:7758)
KRAS-1476靶:5'-TAAAAAGAAAAAAATGGAAAA-3'(SEQ ID NO:7759)
KRAS-1477靶:5'-AAAAAGAAAAAAATGGAAAAA-3'(SEQ ID NO:7760)
KRAS-1478靶:5'-AAAAGAAAAAAATGGAAAAAA-3'(SEQ ID NO:7761)
KRAS-1482靶:5'-GAAAAAAATGGAAAAAAATTA-3'(SEQ ID NO:7762)
KRAS-1483靶:5'-AAAAAAATGGAAAAAAATTAC-3'(SEQ ID NO:7763)
KRAS-1488靶:5'-AATGGAAAAAAATTACAAGGC-3'(SEQ ID NO:7764)
KRAS-1489靶:5'-ATGGAAAAAAATTACAAGGCA-3'(SEQ ID NO:7765)
KRAS-1490靶:5'-TGGAAAAAAATTACAAGGCAA-3'(SEQ ID NO:7766)
KRAS-1525靶:5'-AGGCCATTTCCTTTTCACATT-3'(SEQ ID NO:7767)
KRAS-1531靶:5'-TTTCCTTTTCACATTAGATAA-3'(SEQ ID NO:7768)
KRAS-1538靶:5'-TTCACATTAGATAAATTACTA-3'(SEQ ID NO:7769)
KRAS-1539靶:5'-TCACATTAGATAAATTACTAT-3'(SEQ ID NO:7770)
KRAS-1540靶:5'-CACATTAGATAAATTACTATA-3'(SEQ ID NO:7771)
KRAS-1595靶:5'-CCAGTATGAAATGGGGATTAT-3'(SEQ ID NO:7772)
KRAS-1604靶:5'-AATGGGGATTATTATAGCAAC-3'(SEQ ID NO:7773)
KRAS-1631靶:5'-GGGGCTATATTTACATGCTAC-3'(SEQ ID NO:7774)
KRAS-1632靶:5'-GGGCTATATTTACATGCTACT-3'(SEQ ID NO:7775)
KRAS-1633靶:5'-GGCTATATTTACATGCTACTA-3'(SEQ ID NO:7776)
KRAS-1634靶:5'-GCTATATTTACATGCTACTAA-3'(SEQ ID NO:7777)
KRAS-1635靶:5'-CTATATTTACATGCTACTAAA-3'(SEQ ID NO:7778)
KRAS-1640靶:5'-TTTACATGCTACTAAATTTTT-3'(SEQ ID NO:7779)
KRAS-1647靶:5'-GCTACTAAATTTTTATAATAA-3'(SEQ ID NO:7780)
KRAS-1648靶:5'-CTACTAAATTTTTATAATAAT-3'(SEQ ID NO:7781)
KRAS-1650靶:5'-ACTAAATTTTTATAATAATTG-3'(SEQ ID NO:7782)
KRAS-1651靶:5'-CTAAATTTTTATAATAATTGA-3'(SEQ ID NO:7783)
KRAS-1652靶:5'-TAAATTTTTATAATAATTGAA-3'(SEQ ID NO:7784)
KRAS-1653靶:5'-AAATTTTTATAATAATTGAAA-3'(SEQ ID NO:7785)
KRAS-1654靶:5'-AATTTTTATAATAATTGAAAA-3'(SEQ ID NO:7786)
KRAS-1655靶:5'-ATTTTTATAATAATTGAAAAG-3'(SEQ ID NO:7787)
KRAS-1656靶:5'-TTTTTATAATAATTGAAAAGA-3'(SEQ ID NO:7788)
KRAS-1657靶:5'-TTTTATAATAATTGAAAAGAT-3'(SEQ ID NO:7789)
KRAS-1658靶:5'-TTTATAATAATTGAAAAGATT-3'(SEQ ID NO:7790)
KRAS-1662靶:5'-TAATAATTGAAAAGATTTTAA-3'(SEQ ID NO:7791)
KRAS-1663靶:5'-AATAATTGAAAAGATTTTAAC-3'(SEQ ID NO:7792)
KRAS-1665靶:5'-TAATTGAAAAGATTTTAACAA-3'(SEQ ID NO:7793)
KRAS-1666靶:5'-AATTGAAAAGATTTTAACAAG-3'(SEQ ID NO:7794)
KRAS-1667靶:5'-ATTGAAAAGATTTTAACAAGT-3'(SEQ ID NO:7795)
KRAS-1668靶:5'-TTGAAAAGATTTTAACAAGTA-3'(SEQ ID NO:7796)
KRAS-1669靶:5'-TGAAAAGATTTTAACAAGTAT-3'(SEQ ID NO:7797)
KRAS-1670靶:5'-GAAAAGATTTTAACAAGTATA-3'(SEQ ID NO:7798)
KRAS-1671靶:5'-AAAAGATTTTAACAAGTATAA-3'(SEQ ID NO:7799)
KRAS-1672靶:5'-AAAGATTTTAACAAGTATAAA-3'(SEQ ID NO:7800)
KRAS-1673靶:5'-AAGATTTTAACAAGTATAAAA-3'(SEQ ID NO:7801)
KRAS-1680靶:5'-TAACAAGTATAAAAAATTCTC-3'(SEQ ID NO:7802)
KRAS-1681靶:5'-AACAAGTATAAAAAATTCTCA-3'(SEQ ID NO:7803)
KRAS-1682靶:5'-ACAAGTATAAAAAATTCTCAT-3'(SEQ ID NO:7804)
KRAS-1683靶:5'-CAAGTATAAAAAATTCTCATA-3'(SEQ ID NO:7805)
KRAS-1684靶:5'-AAGTATAAAAAATTCTCATAG-3'(SEQ ID NO:7806)
KRAS-1685靶:5'-AGTATAAAAAATTCTCATAGG-3'(SEQ ID NO:7807)
KRAS-1686靶:5'-GTATAAAAAATTCTCATAGGA-3'(SEQ ID NO:7808)
KRAS-1687靶:5'-TATAAAAAATTCTCATAGGAA-3'(SEQ ID NO:7809)
KRAS-1689靶:5'-TAAAAAATTCTCATAGGAATT-3'(SEQ ID NO:7810)
KRAS-1690靶:5'-AAAAAATTCTCATAGGAATTA-3'(SEQ ID NO:7811)
KRAS-1734靶:5'-TGCTCTTTCATAGTATAACTT-3'(SEQ ID NO:7812)
KRAS-1739靶:5'-TTTCATAGTATAACTTTAAAT-3'(SEQ ID NO:7813)
KRAS-1740靶:5'-TTCATAGTATAACTTTAAATC-3'(SEQ ID NO:7814)
KRAS-1751靶:5'-ACTTTAAATCTTTTCTTCAAC-3'(SEQ ID NO:7815)
KRAS-1752靶:5'-CTTTAAATCTTTTCTTCAACT-3'(SEQ ID NO:7816)
KRAS-1767靶:5'-TCAACTTGAGTCTTTGAAGAT-3'(SEQ ID NO:7817)
KRAS-1769靶:5'-AACTTGAGTCTTTGAAGATAG-3'(SEQ ID NO:7818)
KRAS-1770靶:5'-ACTTGAGTCTTTGAAGATAGT-3'(SEQ ID NO:7819)
KRAS-1781靶:5'-TGAAGATAGTTTTAATTCTGC-3'(SEQ ID NO:7820)
KRAS-1782靶:5'-GAAGATAGTTTTAATTCTGCT-3'(SEQ ID NO:7821)
KRAS-1783靶:5'-AAGATAGTTTTAATTCTGCTT-3'(SEQ ID NO:7822)
KRAS-1797靶:5'-TCTGCTTGTGACATTAAAAGA-3'(SEQ ID NO:7823)
KRAS-2045靶:5'-AGAGCATTGCTTTTGTTTCTT-3'(SEQ ID NO:7824)
KRAS-2046靶:5'-GAGCATTGCTTTTGTTTCTTA-3'(SEQ ID NO:7825)
KRAS-2052靶:5'-TGCTTTTGTTTCTTAAGAAAA-3'(SEQ ID NO:7826)
KRAS-2059靶:5'-GTTTCTTAAGAAAACAAACTC-3'(SEQ ID NO:7827)
KRAS-2060靶:5'-TTTCTTAAGAAAACAAACTCT-3'(SEQ ID NO:7828)
KRAS-2061靶:5'-TTCTTAAGAAAACAAACTCTT-3'(SEQ ID NO:7829)
KRAS-2062靶:5'-TCTTAAGAAAACAAACTCTTT-3'(SEQ ID NO:7830)
KRAS-2063靶:5'-CTTAAGAAAACAAACTCTTTT-3'(SEQ ID NO:7831)
KRAS-2064靶:5'-TTAAGAAAACAAACTCTTTTT-3'(SEQ ID NO:7832)
KRAS-2065靶:5'-TAAGAAAACAAACTCTTTTTT-3'(SEQ ID NO:7833)
KRAS-2069靶:5'-AAAACAAACTCTTTTTTAAAA-3'(SEQ ID NO:7834)
KRAS-2075靶:5'-AACTCTTTTTTAAAAATTACT-3'(SEQ ID NO:7835)
KRAS-2076靶:5'-ACTCTTTTTTAAAAATTACTT-3'(SEQ ID NO:7836)
KRAS-2077靶:5'-CTCTTTTTTAAAAATTACTTT-3'(SEQ ID NO:7837)
KRAS-2078靶:5'-TCTTTTTTAAAAATTACTTTT-3'(SEQ ID NO:7838)
KRAS-2079靶:5'-CTTTTTTAAAAATTACTTTTA-3'(SEQ ID NO:7839)
KRAS-2080靶:5'-TTTTTTAAAAATTACTTTTAA-3'(SEQ ID NO:7840)
KRAS-2081靶:5'-TTTTTAAAAATTACTTTTAAA-3'(SEQ ID NO:7841)
KRAS-2082靶:5'-TTTTAAAAATTACTTTTAAAT-3'(SEQ ID NO:7842)
KRAS-2083靶:5'-TTTAAAAATTACTTTTAAATA-3'(SEQ ID NO:7843)
KRAS-2090靶:5'-ATTACTTTTAAATATTAACTC-3'(SEQ ID NO:7844)
KRAS-2091靶:5'-TTACTTTTAAATATTAACTCA-3'(SEQ ID NO:7845)
KRAS-2093靶:5'-ACTTTTAAATATTAACTCAAA-3'(SEQ ID NO:7846)
KRAS-2095靶:5'-TTTTAAATATTAACTCAAAAG-3'(SEQ ID NO:7847)
KRAS-2096靶:5'-TTTAAATATTAACTCAAAAGT-3'(SEQ ID NO:7848)
KRAS-2097靶:5'-TTAAATATTAACTCAAAAGTT-3'(SEQ ID NO:7849)
KRAS-2098靶:5'-TAAATATTAACTCAAAAGTTG-3'(SEQ ID NO:7850)
KRAS-2132靶:5'-GTGGTGTGCCAAGACATTAAT-3'(SEQ ID NO:7851)
KRAS-2137靶:5'-GTGCCAAGACATTAATTTTTT-3'(SEQ ID NO:7852)
KRAS-2138靶:5'-TGCCAAGACATTAATTTTTTT-3'(SEQ ID NO:7853)
KRAS-2144靶:5'-GACATTAATTTTTTTTTTAAA-3'(SEQ ID NO:7854)
KRAS-2145靶:5'-ACATTAATTTTTTTTTTAAAC-3'(SEQ ID NO:7855)
KRAS-2147靶:5'-ATTAATTTTTTTTTTAAACAA-3'(SEQ ID NO:7856)
KRAS-2149靶:5'-TAATTTTTTTTTTAAACAATG-3'(SEQ ID NO:7857)
KRAS-2150靶:5'-AATTTTTTTTTTAAACAATGA-3'(SEQ ID NO:7858)
KRAS-2151靶:5'-ATTTTTTTTTTAAACAATGAA-3'(SEQ ID NO:7859)
KRAS-2152靶:5'-TTTTTTTTTTAAACAATGAAG-3'(SEQ ID NO:7860)
KRAS-2153靶:5'-TTTTTTTTTAAACAATGAAGT-3'(SEQ ID NO:7861)
KRAS-2155靶:5'-TTTTTTTAAACAATGAAGTGA-3'(SEQ ID NO:7862)
KRAS-2156靶:5'-TTTTTTAAACAATGAAGTGAA-3'(SEQ ID NO:7863)
KRAS-2157靶:5'-TTTTTAAACAATGAAGTGAAA-3'(SEQ ID NO:7864)
KRAS-2165靶:5'-CAATGAAGTGAAAAAGTTTTA-3'(SEQ ID NO:7865)
KRAS-2171靶:5'-AGTGAAAAAGTTTTACAATCT-3'(SEQ ID NO:7866)
KRAS-2172靶:5'-GTGAAAAAGTTTTACAATCTC-3'(SEQ ID NO:7867)
KRAS-2173靶:5'-TGAAAAAGTTTTACAATCTCT-3'(SEQ ID NO:7868)
KRAS-2214靶:5'-ACACTGGTTAAATTAACATTG-3'(SEQ ID NO:7869)
KRAS-2215靶:5'-CACTGGTTAAATTAACATTGC-3'(SEQ ID NO:7870)
KRAS-2216靶:5'-ACTGGTTAAATTAACATTGCA-3'(SEQ ID NO:7871)
KRAS-2227靶:5'-TAACATTGCATAAACACTTTT-3'(SEQ ID NO:7872)
KRAS-2245靶:5'-TTTCAAGTCTGATCCATATTT-3'(SEQ ID NO:7873)
KRAS-2255靶:5'-GATCCATATTTAATAATGCTT-3'(SEQ ID NO:7874)
KRAS-2256靶:5'-ATCCATATTTAATAATGCTTT-3'(SEQ ID NO:7875)
KRAS-2257靶:5'-TCCATATTTAATAATGCTTTA-3'(SEQ ID NO:7876)
KRAS-2258靶:5'-CCATATTTAATAATGCTTTAA-3'(SEQ ID NO:7877)
KRAS-2259靶:5'-CATATTTAATAATGCTTTAAA-3'(SEQ ID NO:7878)
KRAS-2260靶:5'-ATATTTAATAATGCTTTAAAA-3'(SEQ ID NO:7879)
KRAS-2262靶:5'-ATTTAATAATGCTTTAAAATA-3'(SEQ ID NO:7880)
KRAS-2263靶:5'-TTTAATAATGCTTTAAAATAA-3'(SEQ ID NO:7881)
KRAS-2264靶:5'-TTAATAATGCTTTAAAATAAA-3'(SEQ ID NO:7882)
KRAS-2265靶:5'-TAATAATGCTTTAAAATAAAA-3'(SEQ ID NO:7883)
KRAS-2272靶:5'-GCTTTAAAATAAAAATAAAAA-3'(SEQ ID NO:7884)
KRAS-2278靶:5'-AAATAAAAATAAAAACAATCC-3'(SEQ ID NO:7885)
KRAS-2279靶:5'-AATAAAAATAAAAACAATCCT-3'(SEQ ID NO:7886)
KRAS-2280靶:5'-ATAAAAATAAAAACAATCCTT-3'(SEQ ID NO:7887)
KRAS-2281靶:5'-TAAAAATAAAAACAATCCTTT-3'(SEQ ID NO:7888)
KRAS-2282靶:5'-AAAAATAAAAACAATCCTTTT-3'(SEQ ID NO:7889)
KRAS-2283靶:5'-AAAATAAAAACAATCCTTTTG-3'(SEQ ID NO:7890)
KRAS-2284靶:5'-AAATAAAAACAATCCTTTTGA-3'(SEQ ID NO:7891)
KRAS-2285靶:5'-AATAAAAACAATCCTTTTGAT-3'(SEQ ID NO:7892)
KRAS-2289靶:5'-AAAACAATCCTTTTGATAAAT-3'(SEQ ID NO:7893)
KRAS-2294靶:5'-AATCCTTTTGATAAATTTAAA-3'(SEQ ID NO:7894)
KRAS-2295靶:5'-ATCCTTTTGATAAATTTAAAA-3'(SEQ ID NO:7895)
KRAS-2296靶:5'-TCCTTTTGATAAATTTAAAAT-3'(SEQ ID NO:7896)
KRAS-2300靶:5'-TTTGATAAATTTAAAATGTTA-3'(SEQ ID NO:7897)
KRAS-2301靶:5'-TTGATAAATTTAAAATGTTAC-3'(SEQ ID NO:7898)
KRAS-2302靶:5'-TGATAAATTTAAAATGTTACT-3'(SEQ ID NO:7899)
KRAS-2303靶:5'-GATAAATTTAAAATGTTACTT-3'(SEQ ID NO:7900)
KRAS-2304靶:5'-ATAAATTTAAAATGTTACTTA-3'(SEQ ID NO:7901)
KRAS-2305靶:5'-TAAATTTAAAATGTTACTTAT-3'(SEQ ID NO:7902)
KRAS-2307靶:5'-AATTTAAAATGTTACTTATTT-3'(SEQ ID NO:7903)
KRAS-2308靶:5'-ATTTAAAATGTTACTTATTTT-3'(SEQ ID NO:7904)
KRAS-2309靶:5'-TTTAAAATGTTACTTATTTTA-3'(SEQ ID NO:7905)
KRAS-2310靶:5'-TTAAAATGTTACTTATTTTAA-3'(SEQ ID NO:7906)
KRAS-2311靶:5'-TAAAATGTTACTTATTTTAAA-3'(SEQ ID NO:7907)
KRAS-2313靶:5'-AAATGTTACTTATTTTAAAAT-3'(SEQ ID NO:7908)
KRAS-2318靶:5'-TTACTTATTTTAAAATAAATG-3'(SEQ ID NO:7909)
KRAS-2320靶:5'-ACTTATTTTAAAATAAATGAA-3'(SEQ ID NO:7910)
KRAS-2321靶:5'-CTTATTTTAAAATAAATGAAG-3'(SEQ ID NO:7911)
KRAS-2324靶:5'-ATTTTAAAATAAATGAAGTGA-3'(SEQ ID NO:7912)
KRAS-2325靶:5'-TTTTAAAATAAATGAAGTGAG-3'(SEQ ID NO:7913)
KRAS-2445靶:5'-TATCCATTTCTTCATGTTAAA-3'(SEQ ID NO:7914)
KRAS-2446靶:5'-ATCCATTTCTTCATGTTAAAA-3'(SEQ ID NO:7915)
KRAS-2473靶:5'-ATCTCAAACTCTTAGTTTTTT-3'(SEQ ID NO:7916)
KRAS-2483靶:5'-CTTAGTTTTTTTTTTTTACAA-3'(SEQ ID NO:7917)
KRAS-2484靶:5'-TTAGTTTTTTTTTTTTACAAC-3'(SEQ ID NO:7918)
KRAS-2485靶:5'-TAGTTTTTTTTTTTTACAACT-3'(SEQ ID NO:7919)
KRAS-2486靶:5'-AGTTTTTTTTTTTTACAACTA-3'(SEQ ID NO:7920)
KRAS-2487靶:5'-GTTTTTTTTTTTTACAACTAT-3'(SEQ ID NO:7921)
KRAS-2488靶:5'-TTTTTTTTTTTTACAACTATG-3'(SEQ ID NO:7922)
KRAS-2489靶:5'-TTTTTTTTTTTACAACTATGT-3'(SEQ ID NO:7923)
KRAS-2490靶:5'-TTTTTTTTTTACAACTATGTA-3'(SEQ ID NO:7924)
KRAS-2491靶:5'-TTTTTTTTTACAACTATGTAA-3'(SEQ ID NO:7925)
KRAS-2492靶:5'-TTTTTTTTACAACTATGTAAT-3'(SEQ ID NO:7926)
KRAS-2493靶:5'-TTTTTTTACAACTATGTAATT-3'(SEQ ID NO:7927)
KRAS-2500靶:5'-ACAACTATGTAATTTATATTC-3'(SEQ ID NO:7928)
KRAS-2501靶:5'-CAACTATGTAATTTATATTCC-3'(SEQ ID NO:7929)
KRAS-2502靶:5'-AACTATGTAATTTATATTCCA-3'(SEQ ID NO:7930)
KRAS-2508靶:5'-GTAATTTATATTCCATTTACA-3'(SEQ ID NO:7931)
KRAS-2509靶:5'-TAATTTATATTCCATTTACAT-3'(SEQ ID NO:7932)
KRAS-2510靶:5'-AATTTATATTCCATTTACATA-3'(SEQ ID NO:7933)
KRAS-2511靶:5'-ATTTATATTCCATTTACATAA-3'(SEQ ID NO:7934)
KRAS-2523靶:5'-TTTACATAAGGATACACTTAT-3'(SEQ ID NO:7935)
KRAS-2527靶:5'-CATAAGGATACACTTATTTGT-3'(SEQ ID NO:7936)
KRAS-2559靶:5'-CAATCTGTAAATTTTTAACCT-3'(SEQ ID NO:7937)
KRAS-2560靶:5'-AATCTGTAAATTTTTAACCTA-3'(SEQ ID NO:7938)
KRAS-2561靶:5'-ATCTGTAAATTTTTAACCTAT-3'(SEQ ID NO:7939)
KRAS-2617靶:5'-TGTGCAAGAGGTGAAGTTTAT-3'(SEQ ID NO:7940)
KRAS-2619靶:5'-TGCAAGAGGTGAAGTTTATAT-3'(SEQ ID NO:7941)
KRAS-2620靶:5'-GCAAGAGGTGAAGTTTATATT-3'(SEQ ID NO:7942)
KRAS-2622靶:5'-AAGAGGTGAAGTTTATATTTG-3'(SEQ ID NO:7943)
KRAS-2623靶:5'-AGAGGTGAAGTTTATATTTGA-3'(SEQ ID NO:7944)
KRAS-2628靶:5'-TGAAGTTTATATTTGAATATC-3'(SEQ ID NO:7945)
KRAS-2716靶:5'-TGACTTGATGCAGTTTTAATA-3'(SEQ ID NO:7946)
KRAS-2718靶:5'-ACTTGATGCAGTTTTAATACT-3'(SEQ ID NO:7947)
KRAS-2869靶:5'-GGGATTTGACCTAATCACTAA-3'(SEQ ID NO:7948)
KRAS-2875靶:5'-TGACCTAATCACTAATTTTCA-3'(SEQ ID NO:7949)
KRAS-2944靶:5'-GACAGTAGGATTTTTCAAACC-3'(SEQ ID NO:7950)
KRAS-2989靶:5'-CCAGTGGAAGGAGAATTTAAT-3'(SEQ ID NO:7951)
KRAS-2992靶:5'-GTGGAAGGAGAATTTAATAAA-3'(SEQ ID NO:7952)
KRAS-2994靶:5'-GGAAGGAGAATTTAATAAAGA-3'(SEQ ID NO:7953)
KRAS-2995靶:5'-GAAGGAGAATTTAATAAAGAT-3'(SEQ ID NO:7954)
KRAS-2999靶:5'-GAGAATTTAATAAAGATAGTG-3'(SEQ ID NO:7955)
KRAS-3028靶:5'-ATTCCTTAGGTAATCTATAAC-3'(SEQ ID NO:7956)
KRAS-3029靶:5'-TTCCTTAGGTAATCTATAACT-3'(SEQ ID NO:7957)
KRAS-3063靶:5'-GTAACAGTAATACATTCCATT-3'(SEQ ID NO:7958)
KRAS-3065靶:5'-AACAGTAATACATTCCATTGT-3'(SEQ ID NO:7959)
KRAS-3066靶:5'-ACAGTAATACATTCCATTGTT-3'(SEQ ID NO:7960)
KRAS-3067靶:5'-CAGTAATACATTCCATTGTTT-3'(SEQ ID NO:7961)
KRAS-3077靶:5'-TTCCATTGTTTTAGTAACCAG-3'(SEQ ID NO:7962)
KRAS-3091靶:5'-TAACCAGAAATCTTCATGCAA-3'(SEQ ID NO:7963)
KRAS-3101靶:5'-TCTTCATGCAATGAAAAATAC-3'(SEQ ID NO:7964)
KRAS-3108靶:5'-GCAATGAAAAATACTTTAATT-3'(SEQ ID NO:7965)
KRAS-3110靶:5'-AATGAAAAATACTTTAATTCA-3'(SEQ ID NO:7966)
KRAS-3111靶:5'-ATGAAAAATACTTTAATTCAT-3'(SEQ ID NO:7967)
KRAS-3125靶:5'-AATTCATGAAGCTTACTTTTT-3'(SEQ ID NO:7968)
KRAS-3128靶:5'-TCATGAAGCTTACTTTTTTTT-3'(SEQ ID NO:7969)
KRAS-3132靶:5'-GAAGCTTACTTTTTTTTTTTG-3'(SEQ ID NO:7970)
KRAS-3136靶:5'-CTTACTTTTTTTTTTTGGTGT-3'(SEQ ID NO:7971)
KRAS-3137靶:5'-TTACTTTTTTTTTTTGGTGTC-3'(SEQ ID NO:7972)
KRAS-3295靶:5'-TCAACTAATTTTTGTATTTTT-3'(SEQ ID NO:7973)
KRAS-3298靶:5'-ACTAATTTTTGTATTTTTAGG-3'(SEQ ID NO:7974)
KRAS-3411靶:5'-AACTCATTTATTCAGCAAATA-3'(SEQ ID NO:7975)
KRAS-3413靶:5'-CTCATTTATTCAGCAAATATT-3'(SEQ ID NO:7976)
KRAS-3415靶:5'-CATTTATTCAGCAAATATTTA-3'(SEQ ID NO:7977)
KRAS-3587靶:5'-CGTATTTTAGTTTTGCAAAGA-3'(SEQ ID NO:7978)
KRAS-3628靶:5'-AGCTCTATAATTGTTTTGCTA-3'(SEQ ID NO:7979)
KRAS-3675靶:5'-GCTACTTTATGTAAATCACTT-3'(SEQ ID NO:7980)
KRAS-3676靶:5'-CTACTTTATGTAAATCACTTC-3'(SEQ ID NO:7981)
KRAS-3677靶:5'-TACTTTATGTAAATCACTTCA-3'(SEQ ID NO:7982)
KRAS-3678靶:5'-ACTTTATGTAAATCACTTCAT-3'(SEQ ID NO:7983)
KRAS-3679靶:5'-CTTTATGTAAATCACTTCATT-3'(SEQ ID NO:7984)
KRAS-3680靶:5'-TTTATGTAAATCACTTCATTG-3'(SEQ ID NO:7985)
KRAS-3681靶:5'-TTATGTAAATCACTTCATTGT-3'(SEQ ID NO:7986)
KRAS-3695靶:5'-TCATTGTTTTAAAGGAATAAA-3'(SEQ ID NO:7987)
KRAS-3696靶:5'-CATTGTTTTAAAGGAATAAAC-3'(SEQ ID NO:7988)
KRAS-3699靶:5'-TGTTTTAAAGGAATAAACTTG-3'(SEQ ID NO:7989)
KRAS-3700靶:5'-GTTTTAAAGGAATAAACTTGA-3'(SEQ ID NO:7990)
KRAS-3701靶:5'-TTTTAAAGGAATAAACTTGAT-3'(SEQ ID NO:7991)
KRAS-3703靶:5'-TTAAAGGAATAAACTTGATTA-3'(SEQ ID NO:7992)
KRAS-3704靶:5'-TAAAGGAATAAACTTGATTAT-3'(SEQ ID NO:7993)
KRAS-3705靶:5'-AAAGGAATAAACTTGATTATA-3'(SEQ ID NO:7994)
KRAS-3706靶:5'-AAGGAATAAACTTGATTATAT-3'(SEQ ID NO:7995)
KRAS-3707靶:5'-AGGAATAAACTTGATTATATT-3'(SEQ ID NO:7996)
KRAS-3712靶:5'-TAAACTTGATTATATTGTTTT-3'(SEQ ID NO:7997)
KRAS-3713靶:5'-AAACTTGATTATATTGTTTTT-3'(SEQ ID NO:7998)
KRAS-3716靶:5'-CTTGATTATATTGTTTTTTTA-3'(SEQ ID NO:7999)
KRAS-3721靶:5'-TTATATTGTTTTTTTATTTGG-3'(SEQ ID NO:8000)
KRAS-3722靶:5'-TATATTGTTTTTTTATTTGGC-3'(SEQ ID NO:8001)
KRAS-3726靶:5'-TTGTTTTTTTATTTGGCATAA-3'(SEQ ID NO:8002)
KRAS-3727靶:5'-TGTTTTTTTATTTGGCATAAC-3'(SEQ ID NO:8003)
KRAS-3739靶:5'-TGGCATAACTGTGATTCTTTT-3'(SEQ ID NO:8004)
KRAS-3744靶:5'-TAACTGTGATTCTTTTAGGAC-3'(SEQ ID NO:8005)
KRAS-3745靶:5'-AACTGTGATTCTTTTAGGACA-3'(SEQ ID NO:8006)
KRAS-3781靶:5'-AAGGTGTATGTCAGATATTCA-3'(SEQ ID NO:8007)
KRAS-3782靶:5'-AGGTGTATGTCAGATATTCAT-3'(SEQ ID NO:8008)
KRAS-3808靶:5'-CCCAAATGTGTAATATTCCAG-3'(SEQ ID NO:8009)
KRAS-3836靶:5'-TGCATAAGTAATTAAAATATA-3'(SEQ ID NO:8010)
KRAS-3837靶:5'-GCATAAGTAATTAAAATATAC-3'(SEQ ID NO:8011)
KRAS-3838靶:5'-CATAAGTAATTAAAATATACT-3'(SEQ ID NO:8012)
KRAS-3839靶:5'-ATAAGTAATTAAAATATACTT-3'(SEQ ID NO:8013)
KRAS-3840靶:5'-TAAGTAATTAAAATATACTTA-3'(SEQ ID NO:8014)
KRAS-3841靶:5'-AAGTAATTAAAATATACTTAA-3'(SEQ ID NO:8015)
KRAS-3842靶:5'-AGTAATTAAAATATACTTAAA-3'(SEQ ID NO:8016)
KRAS-3843靶:5'-GTAATTAAAATATACTTAAAA-3'(SEQ ID NO:8017)
KRAS-3844靶:5'-TAATTAAAATATACTTAAAAA-3'(SEQ ID NO:8018)
KRAS-3846靶:5'-ATTAAAATATACTTAAAAATT-3'(SEQ ID NO:8019)
KRAS-3847靶:5'-TTAAAATATACTTAAAAATTA-3'(SEQ ID NO:8020)
KRAS-3848靶:5'-TAAAATATACTTAAAAATTAA-3'(SEQ ID NO:8021)
KRAS-3849靶:5'-AAAATATACTTAAAAATTAAT-3'(SEQ ID NO:8022)
KRAS-3853靶:5'-TATACTTAAAAATTAATAGTT-3'(SEQ ID NO:8023)
KRAS-3857靶:5'-CTTAAAAATTAATAGTTTTAT-3'(SEQ ID NO:8024)
KRAS-3858靶:5'-TTAAAAATTAATAGTTTTATC-3'(SEQ ID NO:8025)
KRAS-3859靶:5'-TAAAAATTAATAGTTTTATCT-3'(SEQ ID NO:8026)
KRAS-3874靶:5'-TTATCTGGGTACAAATAAACA-3'(SEQ ID NO:8027)
KRAS-3913靶:5'-CAGACAAGGAAACTTCTATGT-3'(SEQ ID NO:8028)
KRAS-3914靶:5'-AGACAAGGAAACTTCTATGTA-3'(SEQ ID NO:8029)
KRAS-3915靶:5'-GACAAGGAAACTTCTATGTAA-3'(SEQ ID NO:8030)
KRAS-3924靶:5'-ACTTCTATGTAAAAATCACTA-3'(SEQ ID NO:8031)
KRAS-3925靶:5'-CTTCTATGTAAAAATCACTAT-3'(SEQ ID NO:8032)
KRAS-3926靶:5'-TTCTATGTAAAAATCACTATG-3'(SEQ ID NO:8033)
KRAS-3930靶:5'-ATGTAAAAATCACTATGATTT-3'(SEQ ID NO:8034)
KRAS-3931靶:5'-TGTAAAAATCACTATGATTTC-3'(SEQ ID NO:8035)
KRAS-3940靶:5'-CACTATGATTTCTGAATTGCT-3'(SEQ ID NO:8036)
KRAS-3941靶:5'-ACTATGATTTCTGAATTGCTA-3'(SEQ ID NO:8037)
KRAS-3958靶:5'-GCTATGTGAAACTACAGATCT-3'(SEQ ID NO:8038)
KRAS-3959靶:5'-CTATGTGAAACTACAGATCTT-3'(SEQ ID NO:8039)
KRAS-3995靶:5'-GTAGGGTGTTAAGACTTACAC-3'(SEQ ID NO:8040)
KRAS-4082靶:5'-TATTTAGGCCTCTTGAATTTT-3'(SEQ ID NO:8041)
KRAS-4090靶:5'-CCTCTTGAATTTTTGATGTAG-3'(SEQ ID NO:8042)
KRAS-4091靶:5'-CTCTTGAATTTTTGATGTAGA-3'(SEQ ID NO:8043)
KRAS-4106靶:5'-TGTAGATGGGCATTTTTTTAA-3'(SEQ ID NO:8044)
KRAS-4112靶:5'-TGGGCATTTTTTTAAGGTAGT-3'(SEQ ID NO:8045)
KRAS-4124靶:5'-TAAGGTAGTGGTTAATTACCT-3'(SEQ ID NO:8046)
KRAS-4126靶:5'-AGGTAGTGGTTAATTACCTTT-3'(SEQ ID NO:8047)
KRAS-4127靶:5'-GGTAGTGGTTAATTACCTTTA-3'(SEQ ID NO:8048)
KRAS-4128靶:5'-GTAGTGGTTAATTACCTTTAT-3'(SEQ ID NO:8049)
KRAS-4129靶:5'-TAGTGGTTAATTACCTTTATG-3'(SEQ ID NO:8050)
KRAS-4139靶:5'-TTACCTTTATGTGAACTTTGA-3'(SEQ ID NO:8051)
KRAS-4144靶:5'-TTTATGTGAACTTTGAATGGT-3'(SEQ ID NO:8052)
KRAS-4150靶:5'-TGAACTTTGAATGGTTTAACA-3'(SEQ ID NO:8053)
KRAS-4154靶:5'-CTTTGAATGGTTTAACAAAAG-3'(SEQ ID NO:8054)
KRAS-4155靶:5'-TTTGAATGGTTTAACAAAAGA-3'(SEQ ID NO:8055)
KRAS-4156靶:5'-TTGAATGGTTTAACAAAAGAT-3'(SEQ ID NO:8056)
KRAS-4157靶:5'-TGAATGGTTTAACAAAAGATT-3'(SEQ ID NO:8057)
KRAS-4158靶:5'-GAATGGTTTAACAAAAGATTT-3'(SEQ ID NO:8058)
KRAS-4160靶:5'-ATGGTTTAACAAAAGATTTGT-3'(SEQ ID NO:8059)
KRAS-4161靶:5'-TGGTTTAACAAAAGATTTGTT-3'(SEQ ID NO:8060)
KRAS-4165靶:5'-TTAACAAAAGATTTGTTTTTG-3'(SEQ ID NO:8061)
KRAS-4166靶:5'-TAACAAAAGATTTGTTTTTGT-3'(SEQ ID NO:8062)
KRAS-4167靶:5'-AACAAAAGATTTGTTTTTGTA-3'(SEQ ID NO:8063)
KRAS-4169靶:5'-CAAAAGATTTGTTTTTGTAGA-3'(SEQ ID NO:8064)
KRAS-4170靶:5'-AAAAGATTTGTTTTTGTAGAG-3'(SEQ ID NO:8065)
KRAS-4171靶:5'-AAAGATTTGTTTTTGTAGAGA-3'(SEQ ID NO:8066)
KRAS-4172靶:5'-AAGATTTGTTTTTGTAGAGAT-3'(SEQ ID NO:8067)
KRAS-4178靶:5'-TGTTTTTGTAGAGATTTTAAA-3'(SEQ ID NO:8068)
KRAS-4195靶:5'-TAAAGGGGGAGAATTCTAGAA-3'(SEQ ID NO:8069)
KRAS-4197靶:5'-AAGGGGGAGAATTCTAGAAAT-3'(SEQ ID NO:8070)
KRAS-4198靶:5'-AGGGGGAGAATTCTAGAAATA-3'(SEQ ID NO:8071)
KRAS-4199靶:5'-GGGGGAGAATTCTAGAAATAA-3'(SEQ ID NO:8072)
KRAS-4200靶:5'-GGGGAGAATTCTAGAAATAAA-3'(SEQ ID NO:8073)
KRAS-4201靶:5'-GGGAGAATTCTAGAAATAAAT-3'(SEQ ID NO:8074)
KRAS-4206靶:5'-AATTCTAGAAATAAATGTTAC-3'(SEQ ID NO:8075)
KRAS-4207靶:5'-ATTCTAGAAATAAATGTTACC-3'(SEQ ID NO:8076)
KRAS-4208靶:5'-TTCTAGAAATAAATGTTACCT-3'(SEQ ID NO:8077)
KRAS-4209靶:5'-TCTAGAAATAAATGTTACCTA-3'(SEQ ID NO:8078)
KRAS-4210靶:5'-CTAGAAATAAATGTTACCTAA-3'(SEQ ID NO:8079)
KRAS-4212靶:5'-AGAAATAAATGTTACCTAATT-3'(SEQ ID NO:8080)
KRAS-4223靶:5'-TTACCTAATTATTACAGCCTT-3'(SEQ ID NO:8081)
KRAS-4224靶:5'-TACCTAATTATTACAGCCTTA-3'(SEQ ID NO:8082)
KRAS-4238靶:5'-AGCCTTAAAGACAAAAATCCT-3'(SEQ ID NO:8083)
KRAS-4241靶:5'-CTTAAAGACAAAAATCCTTGT-3'(SEQ ID NO:8084)
KRAS-4253靶:5'-AATCCTTGTTGAAGTTTTTTT-3'(SEQ ID NO:8085)
KRAS-4254靶:5'-ATCCTTGTTGAAGTTTTTTTA-3'(SEQ ID NO:8086)
KRAS-4256靶:5'-CCTTGTTGAAGTTTTTTTAAA-3'(SEQ ID NO:8087)
KRAS-4257靶:5'-CTTGTTGAAGTTTTTTTAAAA-3'(SEQ ID NO:8088)
KRAS-4261靶:5'-TTGAAGTTTTTTTAAAAAAAG-3'(SEQ ID NO:8089)
KRAS-4262靶:5'-TGAAGTTTTTTTAAAAAAAGC-3'(SEQ ID NO:8090)
KRAS-4263靶:5'-GAAGTTTTTTTAAAAAAAGCT-3'(SEQ ID NO:8091)
KRAS-4264靶:5'-AAGTTTTTTTAAAAAAAGCTA-3'(SEQ ID NO:8092)
KRAS-4265靶:5'-AGTTTTTTTAAAAAAAGCTAA-3'(SEQ ID NO:8093)
KRAS-4269靶:5'-TTTTTAAAAAAAGCTAAATTA-3'(SEQ ID NO:8094)
KRAS-4271靶:5'-TTTAAAAAAAGCTAAATTACA-3'(SEQ ID NO:8095)
KRAS-4293靶:5'-AGACTTAGGCATTAACATGTT-3'(SEQ ID NO:8096)
KRAS-4294靶:5'-GACTTAGGCATTAACATGTTT-3'(SEQ ID NO:8097)
KRAS-4325靶:5'-ATAGCAGACGTATATTGTATC-3'(SEQ ID NO:8098)
KRAS-4329靶:5'-CAGACGTATATTGTATCATTT-3'(SEQ ID NO:8099)
KRAS-4331靶:5'-GACGTATATTGTATCATTTGA-3'(SEQ ID NO:8100)
KRAS-4334靶:5'-GTATATTGTATCATTTGAGTG-3'(SEQ ID NO:8101)
KRAS-4335靶:5'-TATATTGTATCATTTGAGTGA-3'(SEQ ID NO:8102)
KRAS-4336靶:5'-ATATTGTATCATTTGAGTGAA-3'(SEQ ID NO:8103)
KRAS-4402靶:5'-GCATAGGAATTTAGAACCTAA-3'(SEQ ID NO:8104)
KRAS-4403靶:5'-CATAGGAATTTAGAACCTAAC-3'(SEQ ID NO:8105)
KRAS-4407靶:5'-GGAATTTAGAACCTAACTTTT-3'(SEQ ID NO:8106)
KRAS-4408靶:5'-GAATTTAGAACCTAACTTTTA-3'(SEQ ID NO:8107)
KRAS-4409靶:5'-AATTTAGAACCTAACTTTTAT-3'(SEQ ID NO:8108)
KRAS-4410靶:5'-ATTTAGAACCTAACTTTTATA-3'(SEQ ID NO:8109)
KRAS-4422靶:5'-ACTTTTATAGGTTATCAAAAC-3'(SEQ ID NO:8110)
KRAS-4424靶:5'-TTTTATAGGTTATCAAAACTG-3'(SEQ ID NO:8111)
KRAS-4458靶:5'-ACAATTTTGTCCTAATATATA-3'(SEQ ID NO:8112)
KRAS-4459靶:5'-CAATTTTGTCCTAATATATAC-3'(SEQ ID NO:8113)
KRAS-4460靶:5'-AATTTTGTCCTAATATATACA-3'(SEQ ID NO:8114)
KRAS-4466靶:5'-GTCCTAATATATACATAGAAA-3'(SEQ ID NO:8115)
KRAS-4471靶:5'-AATATATACATAGAAACTTTG-3'(SEQ ID NO:8116)
KRAS-4514靶:5'-TGCACAAGTTCATCTCATTTG-3'(SEQ ID NO:8117)
KRAS-4525靶:5'-ATCTCATTTGTATTCCATTGA-3'(SEQ ID NO:8118)
KRAS-4526靶:5'-TCTCATTTGTATTCCATTGAT-3'(SEQ ID NO:8119)
KRAS-4527靶:5'-CTCATTTGTATTCCATTGATT-3'(SEQ ID NO:8120)
KRAS-4528靶:5'-TCATTTGTATTCCATTGATTT-3'(SEQ ID NO:8121)
KRAS-4529靶:5'-CATTTGTATTCCATTGATTTT-3'(SEQ ID NO:8122)
KRAS-4530靶:5'-ATTTGTATTCCATTGATTTTT-3'(SEQ ID NO:8123)
KRAS-4531靶:5'-TTTGTATTCCATTGATTTTTT-3'(SEQ ID NO:8124)
KRAS-4538靶:5'-TCCATTGATTTTTTTTTTCTT-3'(SEQ ID NO:8125)
KRAS-4539靶:5'-CCATTGATTTTTTTTTTCTTC-3'(SEQ ID NO:8126)
KRAS-4543靶:5'-TGATTTTTTTTTTCTTCTAAA-3'(SEQ ID NO:8127)
KRAS-4544靶:5'-GATTTTTTTTTTCTTCTAAAC-3'(SEQ ID NO:8128)
KRAS-4545靶:5'-ATTTTTTTTTTCTTCTAAACA-3'(SEQ ID NO:8129)
KRAS-4546靶:5'-TTTTTTTTTTCTTCTAAACAT-3'(SEQ ID NO:8130)
KRAS-4547靶:5'-TTTTTTTTTCTTCTAAACATT-3'(SEQ ID NO:8131)
KRAS-4560靶:5'-TAAACATTTTTTCTTCAAACA-3'(SEQ ID NO:8132)
KRAS-4561靶:5'-AAACATTTTTTCTTCAAACAG-3'(SEQ ID NO:8133)
KRAS-4562靶:5'-AACATTTTTTCTTCAAACAGT-3'(SEQ ID NO:8134)
KRAS-4563靶:5'-ACATTTTTTCTTCAAACAGTA-3'(SEQ ID NO:8135)
KRAS-4564靶:5'-CATTTTTTCTTCAAACAGTAT-3'(SEQ ID NO:8136)
KRAS-4571靶:5'-TCTTCAAACAGTATATAACTT-3'(SEQ ID NO:8137)
KRAS-4576靶:5'-AAACAGTATATAACTTTTTTT-3'(SEQ ID NO:8138)
KRAS-4577靶:5'-AACAGTATATAACTTTTTTTA-3'(SEQ ID NO:8139)
KRAS-4578靶:5'-ACAGTATATAACTTTTTTTAG-3'(SEQ ID NO:8140)
KRAS-4579靶:5'-CAGTATATAACTTTTTTTAGG-3'(SEQ ID NO:8141)
KRAS-4585靶:5'-ATAACTTTTTTTAGGGGATTT-3'(SEQ ID NO:8142)
KRAS-4586靶:5'-TAACTTTTTTTAGGGGATTTT-3'(SEQ ID NO:8143)
KRAS-4597靶:5'-AGGGGATTTTTTTTTAGACAG-3'(SEQ ID NO:8144)
KRAS-4598靶:5'-GGGGATTTTTTTTTAGACAGC-3'(SEQ ID NO:8145)
KRAS-4599靶:5'-GGGATTTTTTTTTAGACAGCA-3'(SEQ ID NO:8146)
KRAS-4627靶:5'-TCTGAAGATTTCCATTTGTCA-3'(SEQ ID NO:8147)
KRAS-4628靶:5'-CTGAAGATTTCCATTTGTCAA-3'(SEQ ID NO:8148)
KRAS-4629靶:5'-TGAAGATTTCCATTTGTCAAA-3'(SEQ ID NO:8149)
KRAS-4630靶:5'-GAAGATTTCCATTTGTCAAAA-3'(SEQ ID NO:8150)
KRAS-4635靶:5'-TTTCCATTTGTCAAAAAGTAA-3'(SEQ ID NO:8151)
KRAS-4636靶:5'-TTCCATTTGTCAAAAAGTAAT-3'(SEQ ID NO:8152)
KRAS-4637靶:5'-TCCATTTGTCAAAAAGTAATG-3'(SEQ ID NO:8153)
KRAS-4642靶:5'-TTGTCAAAAAGTAATGATTTC-3'(SEQ ID NO:8154)
KRAS-4643靶:5'-TGTCAAAAAGTAATGATTTCT-3'(SEQ ID NO:8155)
KRAS-4644靶:5'-GTCAAAAAGTAATGATTTCTT-3'(SEQ ID NO:8156)
KRAS-4645靶:5'-TCAAAAAGTAATGATTTCTTG-3'(SEQ ID NO:8157)
KRAS-4647靶:5'-AAAAAGTAATGATTTCTTGAT-3'(SEQ ID NO:8158)
KRAS-4649靶:5'-AAAGTAATGATTTCTTGATAA-3'(SEQ ID NO:8159)
KRAS-4650靶:5'-AAGTAATGATTTCTTGATAAT-3'(SEQ ID NO:8160)
KRAS-4652靶:5'-GTAATGATTTCTTGATAATTG-3'(SEQ ID NO:8161)
KRAS-4653靶:5'-TAATGATTTCTTGATAATTGT-3'(SEQ ID NO:8162)
KRAS-4658靶:5'-ATTTCTTGATAATTGTGTAGT-3'(SEQ ID NO:8163)
KRAS-4659靶:5'-TTTCTTGATAATTGTGTAGTA-3'(SEQ ID NO:8164)
KRAS-4660靶:5'-TTCTTGATAATTGTGTAGTAA-3'(SEQ ID NO:8165)
KRAS-4662靶:5'-CTTGATAATTGTGTAGTAATG-3'(SEQ ID NO:8166)
KRAS-4665靶:5'-GATAATTGTGTAGTAATGTTT-3'(SEQ ID NO:8167)
KRAS-4667靶:5'-TAATTGTGTAGTAATGTTTTT-3'(SEQ ID NO:8168)
KRAS-4668靶:5'-AATTGTGTAGTAATGTTTTTT-3'(SEQ ID NO:8169)
KRAS-4702靶:5'-TACCTTAAAGCTGAATTTATA-3'(SEQ ID NO:8170)
KRAS-4704靶:5'-CCTTAAAGCTGAATTTATATT-3'(SEQ ID NO:8171)
KRAS-4713靶:5'-TGAATTTATATTTAGTAACTT-3'(SEQ ID NO:8172)
KRAS-4714靶:5'-GAATTTATATTTAGTAACTTC-3'(SEQ ID NO:8173)
KRAS-4715靶:5'-AATTTATATTTAGTAACTTCT-3'(SEQ ID NO:8174)
KRAS-4720靶:5'-ATATTTAGTAACTTCTGTGTT-3'(SEQ ID NO:8175)
KRAS-4771靶:5'-AAACTGAATAGCTGTCATAAA-3'(SEQ ID NO:8176)
KRAS-4772靶:5'-AACTGAATAGCTGTCATAAAA-3'(SEQ ID NO:8177)
KRAS-4786靶:5'-CATAAAATGAAACTTTCTTTC-3'(SEQ ID NO:8178)
KRAS-4787靶:5'-ATAAAATGAAACTTTCTTTCT-3'(SEQ ID NO:8179)
KRAS-4788靶:5'-TAAAATGAAACTTTCTTTCTA-3'(SEQ ID NO:8180)
KRAS-4790靶:5'-AAATGAAACTTTCTTTCTAAA-3'(SEQ ID NO:8181)
KRAS-4794靶:5'-GAAACTTTCTTTCTAAAGAAA-3'(SEQ ID NO:8182)
KRAS-4819靶:5'-CTCACATGAGTTCTTGAAGAA-3'(SEQ ID NO:8183)
KRAS-4828靶:5'-GTTCTTGAAGAATAGTCATAA-3'(SEQ ID NO:8184)
KRAS-4829靶:5'-TTCTTGAAGAATAGTCATAAC-3'(SEQ ID NO:8185)
KRAS-4830靶:5'-TCTTGAAGAATAGTCATAACT-3'(SEQ ID NO:8186)
KRAS-4833靶:5'-TGAAGAATAGTCATAACTAGA-3'(SEQ ID NO:8187)
KRAS-4834靶:5'-GAAGAATAGTCATAACTAGAT-3'(SEQ ID NO:8188)
KRAS-4835靶:5'-AAGAATAGTCATAACTAGATT-3'(SEQ ID NO:8189)
KRAS-4836靶:5'-AGAATAGTCATAACTAGATTA-3'(SEQ ID NO:8190)
KRAS-4840靶:5'-TAGTCATAACTAGATTAAGAT-3'(SEQ ID NO:8191)
KRAS-4846靶:5'-TAACTAGATTAAGATCTGTGT-3'(SEQ ID NO:8192)
KRAS-4848靶:5'-ACTAGATTAAGATCTGTGTTT-3'(SEQ ID NO:8193)
KRAS-4849靶:5'-CTAGATTAAGATCTGTGTTTT-3'(SEQ ID NO:8194)
KRAS-4851靶:5'-AGATTAAGATCTGTGTTTTAG-3'(SEQ ID NO:8195)
KRAS-4858靶:5'-GATCTGTGTTTTAGTTTAATA-3'(SEQ ID NO:8196)
KRAS-4859靶:5'-ATCTGTGTTTTAGTTTAATAG-3'(SEQ ID NO:8197)
KRAS-4861靶:5'-CTGTGTTTTAGTTTAATAGTT-3'(SEQ ID NO:8198)
KRAS-4863靶:5'-GTGTTTTAGTTTAATAGTTTG-3'(SEQ ID NO:8199)
KRAS-4864靶:5'-TGTTTTAGTTTAATAGTTTGA-3'(SEQ ID NO:8200)
KRAS-4890靶:5'-CTGTTTGGGATAATGATAGGT-3'(SEQ ID NO:8201)
KRAS-4892靶:5'-GTTTGGGATAATGATAGGTAA-3'(SEQ ID NO:8202)
KRAS-4895靶:5'-TGGGATAATGATAGGTAATTT-3'(SEQ ID NO:8203)
KRAS-4896靶:5'-GGGATAATGATAGGTAATTTA-3'(SEQ ID NO:8204)
KRAS-4899靶:5'-ATAATGATAGGTAATTTAGAT-3'(SEQ ID NO:8205)
KRAS-4900靶:5'-TAATGATAGGTAATTTAGATG-3'(SEQ ID NO:8206)
KRAS-4905靶:5'-ATAGGTAATTTAGATGAATTT-3'(SEQ ID NO:8207)
KRAS-4907靶:5'-AGGTAATTTAGATGAATTTAG-3'(SEQ ID NO:8208)
KRAS-4914靶:5'-TTAGATGAATTTAGGGGAAAA-3'(SEQ ID NO:8209)
KRAS-4915靶:5'-TAGATGAATTTAGGGGAAAAA-3'(SEQ ID NO:8210)
KRAS-4926靶:5'-AGGGGAAAAAAAAGTTATCTG-3'(SEQ ID NO:8211)
KRAS-4927靶:5'-GGGGAAAAAAAAGTTATCTGC-3'(SEQ ID NO:8212)
KRAS-4932靶:5'-AAAAAAAGTTATCTGCAGATA-3'(SEQ ID NO:8213)
KRAS-5033靶:5'-CTGTCTTGTGTTTTCATGTTG-3'(SEQ ID NO:8214)
KRAS-5034靶:5'-TGTCTTGTGTTTTCATGTTGA-3'(SEQ ID NO:8215)
KRAS-5035靶:5'-GTCTTGTGTTTTCATGTTGAA-3'(SEQ ID NO:8216)
KRAS-5045靶:5'-TTCATGTTGAAAATACTTTTG-3'(SEQ ID NO:8217)
KRAS-5046靶:5'-TCATGTTGAAAATACTTTTGC-3'(SEQ ID NO:8218)
KRAS-5047靶:5'-CATGTTGAAAATACTTTTGCA-3'(SEQ ID NO:8219)
KRAS-5048靶:5'-ATGTTGAAAATACTTTTGCAT-3'(SEQ ID NO:8220)
KRAS-5058靶:5'-TACTTTTGCATTTTTCCTTTG-3'(SEQ ID NO:8221)
KRAS-5075靶:5'-TTTGAGTGCCAATTTCTTACT-3'(SEQ ID NO:8222)
KRAS-5080靶:5'-GTGCCAATTTCTTACTAGTAC-3'(SEQ ID NO:8223)
KRAS-5081靶:5'-TGCCAATTTCTTACTAGTACT-3'(SEQ ID NO:8224)
KRAS-5090靶:5'-CTTACTAGTACTATTTCTTAA-3'(SEQ ID NO:8225)
KRAS-5091靶:5'-TTACTAGTACTATTTCTTAAT-3'(SEQ ID NO:8226)
KRAS-5096靶:5'-AGTACTATTTCTTAATGTAAC-3'(SEQ ID NO:8227)
KRAS-5097靶:5'-GTACTATTTCTTAATGTAACA-3'(SEQ ID NO:8228)
KRAS-5098靶:5'-TACTATTTCTTAATGTAACAT-3'(SEQ ID NO:8229)
KRAS-5105靶:5'-TCTTAATGTAACATGTTTACC-3'(SEQ ID NO:8230)
KRAS-5122靶:5'-TACCTGGAATGTATTTTAACT-3'(SEQ ID NO:8231)
KRAS-5124靶:5'-CCTGGAATGTATTTTAACTAT-3'(SEQ ID NO:8232)
KRAS-5125靶:5'-CTGGAATGTATTTTAACTATT-3'(SEQ ID NO:8233)
KRAS-5126靶:5'-TGGAATGTATTTTAACTATTT-3'(SEQ ID NO:8234)
KRAS-5127靶:5'-GGAATGTATTTTAACTATTTT-3'(SEQ ID NO:8235)
KRAS-5129靶:5'-AATGTATTTTAACTATTTTTG-3'(SEQ ID NO:8236)
KRAS-5131靶:5'-TGTATTTTAACTATTTTTGTA-3'(SEQ ID NO:8237)
KRAS-5132靶:5'-GTATTTTAACTATTTTTGTAT-3'(SEQ ID NO:8238)
KRAS-5133靶:5'-TATTTTAACTATTTTTGTATA-3'(SEQ ID NO:8239)
KRAS-5140靶:5'-ACTATTTTTGTATAGTGTAAA-3'(SEQ ID NO:8240)
KRAS-5141靶:5'-CTATTTTTGTATAGTGTAAAC-3'(SEQ ID NO:8241)
KRAS-5142靶:5'-TATTTTTGTATAGTGTAAACT-3'(SEQ ID NO:8242)
KRAS-5157靶:5'-TAAACTGAAACATGCACATTT-3'(SEQ ID NO:8243)
KRAS-5163靶:5'-GAAACATGCACATTTTGTACA-3'(SEQ ID NO:8244)
KRAS-5216靶:5'-GATCCAGTTGTTTTCCATCAT-3'(SEQ ID NO:8245)
KRAS-5218靶:5'-TCCAGTTGTTTTCCATCATTT-3'(SEQ ID NO:8246)
KRAS-5255靶:5'-GAATGTTGGTCATATCAAACA-3'(SEQ ID NO:8247)
KRAS-5256靶:5'-AATGTTGGTCATATCAAACAT-3'(SEQ ID NO:8248)
KRAS-5257靶:5'-ATGTTGGTCATATCAAACATT-3'(SEQ ID NO:8249)
KRAS-5261靶:5'-TGGTCATATCAAACATTAAAA-3'(SEQ ID NO:8250)
KRAS-5277靶:5'-TAAAAATGACCACTCTTTTAA-3'(SEQ ID NO:8251)
KRAS-5278靶:5'-AAAAATGACCACTCTTTTAAT-3'(SEQ ID NO:8252)
KRAS-5287靶:5'-CACTCTTTTAATTGAAATTAA-3'(SEQ ID NO:8253)
KRAS-5288靶:5'-ACTCTTTTAATTGAAATTAAC-3'(SEQ ID NO:8254)
KRAS-5290靶:5'-TCTTTTAATTGAAATTAACTT-3'(SEQ ID NO:8255)
KRAS-5292靶:5'-TTTTAATTGAAATTAACTTTT-3'(SEQ ID NO:8256)
KRAS-5293靶:5'-TTTAATTGAAATTAACTTTTA-3'(SEQ ID NO:8257)
KRAS-5294靶:5'-TTAATTGAAATTAACTTTTAA-3'(SEQ ID NO:8258)
KRAS-5295靶:5'-TAATTGAAATTAACTTTTAAA-3'(SEQ ID NO:8259)
KRAS-5296靶:5'-AATTGAAATTAACTTTTAAAT-3'(SEQ ID NO:8260)
KRAS-5297靶:5'-ATTGAAATTAACTTTTAAATG-3'(SEQ ID NO:8261)
KRAS-5300靶:5'-GAAATTAACTTTTAAATGTTT-3'(SEQ ID NO:8262)
KRAS-5304靶:5'-TTAACTTTTAAATGTTTATAG-3'(SEQ ID NO:8263)
KRAS-5308靶:5'-CTTTTAAATGTTTATAGGAGT-3'(SEQ ID NO:8264)
KRAS-5309靶:5'-TTTTAAATGTTTATAGGAGTA-3'(SEQ ID NO:8265)
KRAS-5331靶:5'-GTGCTGTGAAGTGATCTAAAA-3'(SEQ ID NO:8266)
KRAS-5333靶:5'-GCTGTGAAGTGATCTAAAATT-3'(SEQ ID NO:8267)
KRAS-5334靶:5'-CTGTGAAGTGATCTAAAATTT-3'(SEQ ID NO:8268)
KRAS-5335靶:5'-TGTGAAGTGATCTAAAATTTG-3'(SEQ ID NO:8269)
KRAS-5336靶:5'-GTGAAGTGATCTAAAATTTGT-3'(SEQ ID NO:8270)
KRAS-5337靶:5'-TGAAGTGATCTAAAATTTGTA-3'(SEQ ID NO:8271)
KRAS-5338靶:5'-GAAGTGATCTAAAATTTGTAA-3'(SEQ ID NO:8272)
KRAS-5342靶:5'-TGATCTAAAATTTGTAATATT-3'(SEQ ID NO:8273)
KRAS-5343靶:5'-GATCTAAAATTTGTAATATTT-3'(SEQ ID NO:8274)
KRAS-5347靶:5'-TAAAATTTGTAATATTTTTGT-3'(SEQ ID NO:8275)
KRAS-5348靶:5'-AAAATTTGTAATATTTTTGTC-3'(SEQ ID NO:8276)
KRAS-5349靶:5'-AAATTTGTAATATTTTTGTCA-3'(SEQ ID NO:8277)
KRAS-5353靶:5'-TTGTAATATTTTTGTCATGAA-3'(SEQ ID NO:8278)
KRAS-5354靶:5'-TGTAATATTTTTGTCATGAAC-3'(SEQ ID NO:8279)
KRAS-5370靶:5'-TGAACTGTACTACTCCTAATT-3'(SEQ ID NO:8280)
KRAS-5371靶:5'-GAACTGTACTACTCCTAATTA-3'(SEQ ID NO:8281)
KRAS-5381靶:5'-ACTCCTAATTATTGTAATGTA-3'(SEQ ID NO:8282)
KRAS-5382靶:5'-CTCCTAATTATTGTAATGTAA-3'(SEQ ID NO:8283)
KRAS-5384靶:5'-CCTAATTATTGTAATGTAATA-3'(SEQ ID NO:8284)
KRAS-5386靶:5'-TAATTATTGTAATGTAATAAA-3'(SEQ ID NO:8285)
KRAS-5387靶:5'-AATTATTGTAATGTAATAAAA-3'(SEQ ID NO:8286)
KRAS-5389靶:5'-TTATTGTAATGTAATAAAAAT-3'(SEQ ID NO:8287)
KRAS-5390靶:5'-TATTGTAATGTAATAAAAATA-3'(SEQ ID NO:8288)
KRAS-5394靶:5'-GTAATGTAATAAAAATAGTTA-3'(SEQ ID NO:8289)
KRAS-5395靶:5'-TAATGTAATAAAAATAGTTAC-3'(SEQ ID NO:8290)
KRAS-5396靶:5'-AATGTAATAAAAATAGTTACA-3'(SEQ ID NO:8291)
KRAS-5404靶:5'-AAAAATAGTTACAGTGACAAA-3'(SEQ ID NO:8292)
KRAS-5405靶:5'-AAAATAGTTACAGTGACAAAA-3'(SEQ ID NO:8293)
KRAS-5407靶:5'-AATAGTTACAGTGACAAAAAA-3'(SEQ ID NO:8294)
KRAS-166靶:5'-GAGAGGCCTGCTGAAAATGAC-3'(SEQ ID NO:8295)
KRAS-167靶:5'-AGAGGCCTGCTGAAAATGACT-3'(SEQ ID NO:8296)
KRAS-168靶:5'-GAGGCCTGCTGAAAATGACTG-3'(SEQ ID NO:8297)
KRAS-169靶:5'-AGGCCTGCTGAAAATGACTGA-3'(SEQ ID NO:8298)
KRAS-204靶:5'-TAGTTGGAGCTGGTGGCGTAG-3'(SEQ ID NO:8299)
KRAS-205靶:5'-AGTTGGAGCTGGTGGCGTAGG-3'(SEQ ID NO:8300)
KRAS-206靶:5'-GTTGGAGCTGGTGGCGTAGGC-3'(SEQ ID NO:8301)
KRAS-207靶:5'-TTGGAGCTGGTGGCGTAGGCA-3'(SEQ ID NO:8302)
KRAS-208靶:5'-TGGAGCTGGTGGCGTAGGCAA-3'(SEQ ID NO:8303)
KRAS-209靶:5'-GGAGCTGGTGGCGTAGGCAAG-3'(SEQ ID NO:8304)
KRAS-210靶:5'-GAGCTGGTGGCGTAGGCAAGA-3'(SEQ ID NO:8305)
KRAS-241靶:5'-GATACAGCTAATTCAGAATCA-3'(SEQ ID NO:8306)
KRAS-313靶:5'-AGTAATTGATGGAGAAACCTG-3'(SEQ ID NO:8307)
KRAS-314靶:5'-GTAATTGATGGAGAAACCTGT-3'(SEQ ID NO:8308)
KRAS-318靶:5'-TTGATGGAGAAACCTGTCTCT-3'(SEQ ID NO:8309)
KRAS-328靶:5'-AACCTGTCTCTTGGATATTCT-3'(SEQ ID NO:8310)
KRAS-330靶:5'-CCTGTCTCTTGGATATTCTCG-3'(SEQ ID NO:8311)
KRAS-331靶:5'-CTGTCTCTTGGATATTCTCGA-3'(SEQ ID NO:8312)
KRAS-332靶:5'-TGTCTCTTGGATATTCTCGAC-3'(SEQ ID NO:8313)
KRAS-333靶:5'-GTCTCTTGGATATTCTCGACA-3'(SEQ ID NO:8314)
KRAS-334靶:5'-TCTCTTGGATATTCTCGACAC-3'(SEQ ID NO:8315)
KRAS-335靶:5'-CTCTTGGATATTCTCGACACA-3'(SEQ ID NO:8316)
KRAS-336靶:5'-TCTTGGATATTCTCGACACAG-3'(SEQ ID NO:8317)
KRAS-352靶:5'-CACAGCAGGTCAAGAGGAGTA-3'(SEQ ID NO:8318)
KRAS-353靶:5'-ACAGCAGGTCAAGAGGAGTAC-3'(SEQ ID NO:8319)
KRAS-354靶:5'-CAGCAGGTCAAGAGGAGTACA-3'(SEQ ID NO:8320)
KRAS-364靶:5'-AGAGGAGTACAGTGCAATGAG-3'(SEQ ID NO:8321)
KRAS-365靶:5'-GAGGAGTACAGTGCAATGAGG-3'(SEQ ID NO:8322)
KRAS-366靶:5'-AGGAGTACAGTGCAATGAGGG-3'(SEQ ID NO:8323)
KRAS-367靶:5'-GGAGTACAGTGCAATGAGGGA-3'(SEQ ID NO:8324)
KRAS-368靶:5'-GAGTACAGTGCAATGAGGGAC-3'(SEQ ID NO:8325)
KRAS-369靶:5'-AGTACAGTGCAATGAGGGACC-3'(SEQ ID NO:8326)
KRAS-370靶:5'-GTACAGTGCAATGAGGGACCA-3'(SEQ ID NO:8327)
KRAS-371靶:5'-TACAGTGCAATGAGGGACCAG-3'(SEQ ID NO:8328)
KRAS-372靶:5'-ACAGTGCAATGAGGGACCAGT-3'(SEQ ID NO:8329)
KRAS-420靶:5'-GTGTATTTGCCATAAATAATA-3'(SEQ ID NO:8330)
KRAS-421靶:5'-TGTATTTGCCATAAATAATAC-3'(SEQ ID NO:8331)
KRAS-422靶:5'-GTATTTGCCATAAATAATACT-3'(SEQ ID NO:8332)
KRAS-423靶:5'-TATTTGCCATAAATAATACTA-3'(SEQ ID NO:8333)
KRAS-424靶:5'-ATTTGCCATAAATAATACTAA-3'(SEQ ID NO:8334)
KRAS-425靶:5'-TTTGCCATAAATAATACTAAA-3'(SEQ ID NO:8335)
KRAS-426靶:5'-TTGCCATAAATAATACTAAAT-3'(SEQ ID NO:8336)
KRAS-436靶:5'-TAATACTAAATCATTTGAAGA-3'(SEQ ID NO:8337)
KRAS-437靶:5'-AATACTAAATCATTTGAAGAT-3'(SEQ ID NO:8338)
KRAS-438靶:5'-ATACTAAATCATTTGAAGATA-3'(SEQ ID NO:8339)
KRAS-439靶:5'-TACTAAATCATTTGAAGATAT-3'(SEQ ID NO:8340)
KRAS-440靶:5'-ACTAAATCATTTGAAGATATT-3'(SEQ ID NO:8341)
KRAS-441靶:5'-CTAAATCATTTGAAGATATTC-3'(SEQ ID NO:8342)
KRAS-442靶:5'-TAAATCATTTGAAGATATTCA-3'(SEQ ID NO:8343)
KRAS-443靶:5'-AAATCATTTGAAGATATTCAC-3'(SEQ ID NO:8344)
KRAS-444靶:5'-AATCATTTGAAGATATTCACC-3'(SEQ ID NO:8345)
KRAS-454靶:5'-AGATATTCACCATTATAGAGA-3'(SEQ ID NO:8346)
KRAS-455靶:5'-GATATTCACCATTATAGAGAA-3'(SEQ ID NO:8347)
KRAS-456靶:5'-ATATTCACCATTATAGAGAAC-3'(SEQ ID NO:8348)
KRAS-457靶:5'-TATTCACCATTATAGAGAACA-3'(SEQ ID NO:8349)
KRAS-458靶:5'-ATTCACCATTATAGAGAACAA-3'(SEQ ID NO:8350)
KRAS-459靶:5'-TTCACCATTATAGAGAACAAA-3'(SEQ ID NO:8351)
KRAS-460靶:5'-TCACCATTATAGAGAACAAAT-3'(SEQ ID NO:8352)
KRAS-461靶:5'-CACCATTATAGAGAACAAATT-3'(SEQ ID NO:8353)
KRAS-462靶:5'-ACCATTATAGAGAACAAATTA-3'(SEQ ID NO:8354)
KRAS-508靶:5'-ACCTATGGTCCTAGTAGGAAA-3'(SEQ ID NO:8355)
KRAS-531靶:5'-AATGTGATTTGCCTTCTAGAA-3'(SEQ ID NO:8356)
KRAS-532靶:5'-ATGTGATTTGCCTTCTAGAAC-3'(SEQ ID NO:8357)
KRAS-534靶:5'-GTGATTTGCCTTCTAGAACAG-3'(SEQ ID NO:8358)
KRAS-586靶:5'-AAGTTATGGAATTCCTTTTAT-3'(SEQ ID NO:8359)
KRAS-587靶:5'-AGTTATGGAATTCCTTTTATT-3'(SEQ ID NO:8360)
KRAS-588靶:5'-GTTATGGAATTCCTTTTATTG-3'(SEQ ID NO:8361)
KRAS-763靶:5'-ATGATGCCTTCTATACATTAG-3'(SEQ ID NO:8362)
KRAS-764靶:5'-TGATGCCTTCTATACATTAGT-3'(SEQ ID NO:8363)
KRAS-784靶:5'-TTCGAGAAATTCGAAAACATA-3'(SEQ ID NO:8364)
KRAS-794靶:5'-TCGAAAACATAAAGAAAAGAT-3'(SEQ ID NO:8365)
KRAS-795靶:5'-CGAAAACATAAAGAAAAGATG-3'(SEQ ID NO:8366)
KRAS-796靶:5'-GAAAACATAAAGAAAAGATGA-3'(SEQ ID NO:8367)
KRAS-797靶:5'-AAAACATAAAGAAAAGATGAG-3'(SEQ ID NO:8368)
KRAS-798靶:5'-AAACATAAAGAAAAGATGAGC-3'(SEQ ID NO:8369)
KRAS-799靶:5'-AACATAAAGAAAAGATGAGCA-3'(SEQ ID NO:8370)
KRAS-800靶:5'-ACATAAAGAAAAGATGAGCAA-3'(SEQ ID NO:8371)
KRAS-801靶:5'-CATAAAGAAAAGATGAGCAAA-3'(SEQ ID NO:8372)
KRAS-802靶:5'-ATAAAGAAAAGATGAGCAAAG-3'(SEQ ID NO:8373)
KRAS-908靶:5'-ACAAGTGGTAATTTTTGTACA-3'(SEQ ID NO:8374)
KRAS-909靶:5'-CAAGTGGTAATTTTTGTACAT-3'(SEQ ID NO:8375)
KRAS-920靶:5'-TTTTGTACATTACACTAAATT-3'(SEQ ID NO:8376)
KRAS-921靶:5'-TTTGTACATTACACTAAATTA-3'(SEQ ID NO:8377)
KRAS-922靶:5'-TTGTACATTACACTAAATTAT-3'(SEQ ID NO:8378)
KRAS-923靶:5'-TGTACATTACACTAAATTATT-3'(SEQ ID NO:8379)
KRAS-924靶:5'-GTACATTACACTAAATTATTA-3'(SEQ ID NO:8380)
KRAS-925靶:5'-TACATTACACTAAATTATTAG-3'(SEQ ID NO:8381)
KRAS-926靶:5'-ACATTACACTAAATTATTAGC-3'(SEQ ID NO:8382)
KRAS-927靶:5'-CATTACACTAAATTATTAGCA-3'(SEQ ID NO:8383)
KRAS-928靶:5'-ATTACACTAAATTATTAGCAT-3'(SEQ ID NO:8384)
KRAS-938靶:5'-ATTATTAGCATTTGTTTTAGC-3'(SEQ ID NO:8385)
KRAS-939靶:5'-TTATTAGCATTTGTTTTAGCA-3'(SEQ ID NO:8386)
KRAS-940靶:5'-TATTAGCATTTGTTTTAGCAT-3'(SEQ ID NO:8387)
KRAS-941靶:5'-ATTAGCATTTGTTTTAGCATT-3'(SEQ ID NO:8388)
KRAS-942靶:5'-TTAGCATTTGTTTTAGCATTA-3'(SEQ ID NO:8389)
KRAS-943靶:5'-TAGCATTTGTTTTAGCATTAC-3'(SEQ ID NO:8390)
KRAS-944靶:5'-AGCATTTGTTTTAGCATTACC-3'(SEQ ID NO:8391)
KRAS-945靶:5'-GCATTTGTTTTAGCATTACCT-3'(SEQ ID NO:8392)
KRAS-946靶:5'-CATTTGTTTTAGCATTACCTA-3'(SEQ ID NO:8393)
KRAS-1010靶:5'-TGCTTATTTTAAAATGACAGT-3'(SEQ ID NO:8394)
KRAS-1012靶:5'-CTTATTTTAAAATGACAGTGG-3'(SEQ ID NO:8395)
KRAS-1045靶:5'-CCTCTAAGTGCCAGTATTCCC-3'(SEQ ID NO:8396)
KRAS-1197靶:5'-AACAAATTAATGAAGCTTTTG-3'(SEQ ID NO:8397)
KRAS-1198靶:5'-ACAAATTAATGAAGCTTTTGA-3'(SEQ ID NO:8398)
KRAS-1230靶:5'-TCTGTGTTTTATCTAGTCACA-3'(SEQ ID NO:8399)
KRAS-1231靶:5'-CTGTGTTTTATCTAGTCACAT-3'(SEQ ID NO:8400)
KRAS-1234靶:5'-TGTTTTATCTAGTCACATAAA-3'(SEQ ID NO:8401)
KRAS-1249靶:5'-CATAAATGGATTAATTACTAA-3'(SEQ ID NO:8402)
KRAS-1250靶:5'-ATAAATGGATTAATTACTAAT-3'(SEQ ID NO:8403)
KRAS-1287靶:5'-TAATTGGTTTTTACTGAAACA-3'(SEQ ID NO:8404)
KRAS-1527靶:5'-GCCATTTCCTTTTCACATTAG-3'(SEQ ID NO:8405)
KRAS-1533靶:5'-TCCTTTTCACATTAGATAAAT-3'(SEQ ID NO:8406)
KRAS-1540靶:5'-CACATTAGATAAATTACTATA-3'(SEQ ID NO:8407)
KRAS-1541靶:5'-ACATTAGATAAATTACTATAA-3'(SEQ ID NO:8408)
KRAS-1542靶:5'-CATTAGATAAATTACTATAAA-3'(SEQ ID NO:8409)
KRAS-1583靶:5'-GTTAAGGCAGACCCAGTATGA-3'(SEQ ID NO:8410)
KRAS-1584靶:5'-TTAAGGCAGACCCAGTATGAA-3'(SEQ ID NO:8411)
KRAS-1585靶:5'-TAAGGCAGACCCAGTATGAAA-3'(SEQ ID NO:8412)
KRAS-1586靶:5'-AAGGCAGACCCAGTATGAAAT-3'(SEQ ID NO:8413)
KRAS-1597靶:5'-AGTATGAAATGGGGATTATTA-3'(SEQ ID NO:8414)
KRAS-1606靶:5'-TGGGGATTATTATAGCAACCA-3'(SEQ ID NO:8415)
KRAS-1630靶:5'-TGGGGCTATATTTACATGCTA-3'(SEQ ID NO:8416)
KRAS-1631靶:5'-GGGGCTATATTTACATGCTAC-3'(SEQ ID NO:8417)
KRAS-1632靶:5'-GGGCTATATTTACATGCTACT-3'(SEQ ID NO:8418)
KRAS-1633靶:5'-GGCTATATTTACATGCTACTA-3'(SEQ ID NO:8419)
KRAS-1634靶:5'-GCTATATTTACATGCTACTAA-3'(SEQ ID NO:8420)
KRAS-1635靶:5'-CTATATTTACATGCTACTAAA-3'(SEQ ID NO:8421)
KRAS-1636靶:5'-TATATTTACATGCTACTAAAT-3'(SEQ ID NO:8422)
KRAS-1637靶:5'-ATATTTACATGCTACTAAATT-3'(SEQ ID NO:8423)
KRAS-1638靶:5'-TATTTACATGCTACTAAATTT-3'(SEQ ID NO:8424)
KRAS-1639靶:5'-ATTTACATGCTACTAAATTTT-3'(SEQ ID NO:8425)
KRAS-1640靶:5'-TTTACATGCTACTAAATTTTT-3'(SEQ ID NO:8426)
KRAS-1736靶:5'-CTCTTTCATAGTATAACTTTA-3'(SEQ ID NO:8427)
KRAS-1741靶:5'-TCATAGTATAACTTTAAATCT-3'(SEQ ID NO:8428)
KRAS-1742靶:5'-CATAGTATAACTTTAAATCTT-3'(SEQ ID NO:8429)
KRAS-1753靶:5'-TTTAAATCTTTTCTTCAACTT-3'(SEQ ID NO:8430)
KRAS-1754靶:5'-TTAAATCTTTTCTTCAACTTG-3'(SEQ ID NO:8431)
KRAS-1769靶:5'-AACTTGAGTCTTTGAAGATAG-3'(SEQ ID NO:8432)
KRAS-1771靶:5'-CTTGAGTCTTTGAAGATAGTT-3'(SEQ ID NO:8433)
KRAS-1772靶:5'-TTGAGTCTTTGAAGATAGTTT-3'(SEQ ID NO:8434)
KRAS-1783靶:5'-AAGATAGTTTTAATTCTGCTT-3'(SEQ ID NO:8435)
KRAS-1784靶:5'-AGATAGTTTTAATTCTGCTTG-3'(SEQ ID NO:8436)
KRAS-1785靶:5'-GATAGTTTTAATTCTGCTTGT-3'(SEQ ID NO:8437)
KRAS-1799靶:5'-TGCTTGTGACATTAAAAGATT-3'(SEQ ID NO:8438)
KRAS-2100靶:5'-AATATTAACTCAAAAGTTGAG-3'(SEQ ID NO:8439)
KRAS-2134靶:5'-GGTGTGCCAAGACATTAATTT-3'(SEQ ID NO:8440)
KRAS-2216靶:5'-ACTGGTTAAATTAACATTGCA-3'(SEQ ID NO:8441)
KRAS-2217靶:5'-CTGGTTAAATTAACATTGCAT-3'(SEQ ID NO:8442)
KRAS-2218靶:5'-TGGTTAAATTAACATTGCATA-3'(SEQ ID NO:8443)
KRAS-2229靶:5'-ACATTGCATAAACACTTTTCA-3'(SEQ ID NO:8444)
KRAS-2247靶:5'-TCAAGTCTGATCCATATTTAA-3'(SEQ ID NO:8445)
KRAS-2326靶:5'-TTTAAAATAAATGAAGTGAGA-3'(SEQ ID NO:8446)
KRAS-2327靶:5'-TTAAAATAAATGAAGTGAGAT-3'(SEQ ID NO:8447)
KRAS-2547靶:5'-TCAAGCTCAGCACAATCTGTA-3'(SEQ ID NO:8448)
KRAS-2548靶:5'-CAAGCTCAGCACAATCTGTAA-3'(SEQ ID NO:8449)
KRAS-3741靶:5'-GCATAACTGTGATTCTTTTAG-3'(SEQ ID NO:8450)
KRAS-3746靶:5'-ACTGTGATTCTTTTAGGACAA-3'(SEQ ID NO:8451)
KRAS-3747靶:5'-CTGTGATTCTTTTAGGACAAT-3'(SEQ ID NO:8452)
KRAS-3783靶:5'-GGTGTATGTCAGATATTCATA-3'(SEQ ID NO:8453)
KRAS-3784靶:5'-GTGTATGTCAGATATTCATAT-3'(SEQ ID NO:8454)
KRAS-3810靶:5'-CAAATGTGTAATATTCCAGTT-3'(SEQ ID NO:8455)
KRAS-4396靶:5'-CACACTGCATAGGAATTTAGA-3'(SEQ ID NO:8456)
KRAS-4447靶:5'-GTCACCATTGCACAATTTTGT-3'(SEQ ID NO:8457)
KRAS-4448靶:5'-TCACCATTGCACAATTTTGTC-3'(SEQ ID NO:8458)
KRAS-4449靶:5'-CACCATTGCACAATTTTGTCC-3'(SEQ ID NO:8459)
KRAS-4450靶:5'-ACCATTGCACAATTTTGTCCT-3'(SEQ ID NO:8460)
KRAS-4451靶:5'-CCATTGCACAATTTTGTCCTA-3'(SEQ ID NO:8461)
KRAS-4452靶:5'-CATTGCACAATTTTGTCCTAA-3'(SEQ ID NO:8462)
KRAS-4748靶:5'-GATAGCATGAATTCTGCATTG-3'(SEQ ID NO:8463)
KRAS-4749靶:5'-ATAGCATGAATTCTGCATTGA-3'(SEQ ID NO:8464)
KRAS-4878靶:5'-AGTTTGAAGTGCCTGTTTGGG-3'(SEQ ID NO:8465)
KRAS-4879靶:5'-GTTTGAAGTGCCTGTTTGGGA-3'(SEQ ID NO:8466)
KRAS-4880靶:5'-TTTGAAGTGCCTGTTTGGGAT-3'(SEQ ID NO:8467)
KRAS-5073靶:5'-CCTTTGAGTGCCAATTTCTTA-3'(SEQ ID NO:8468)
KRAS-5074靶:5'-CTTTGAGTGCCAATTTCTTAC-3'(SEQ ID NO:8469)
KRAS-5075靶:5'-TTTGAGTGCCAATTTCTTACT-3'(SEQ ID NO:8470)
KRAS-5076靶:5'-TTGAGTGCCAATTTCTTACTA-3'(SEQ ID NO:8471)
KRAS-5077靶:5'-TGAGTGCCAATTTCTTACTAG-3'(SEQ ID NO:8472)
KRAS-5078靶:5'-GAGTGCCAATTTCTTACTAGT-3'(SEQ ID NO:8473)
KRAS-5128靶:5'-GAATGTATTTTAACTATTTTT-3'(SEQ ID NO:8474)
KRAS-5129靶:5'-AATGTATTTTAACTATTTTTG-3'(SEQ ID NO:8475)
KRAS-5138靶:5'-TAACTATTTTTGTATAGTGTA-3'(SEQ ID NO:8476)
KRAS-5139靶:5'-AACTATTTTTGTATAGTGTAA-3'(SEQ ID NO:8477)
KRAS-5140靶:5'-ACTATTTTTGTATAGTGTAAA-3'(SEQ ID NO:8478)
KRAS-5141靶:5'-CTATTTTTGTATAGTGTAAAC-3'(SEQ ID NO:8479)
KRAS-5142靶:5'-TATTTTTGTATAGTGTAAACT-3'(SEQ ID NO:8480)
KRAS-5143靶:5'-ATTTTTGTATAGTGTAAACTG-3'(SEQ ID NO:8481)
KRAS-5163靶:5'-GAAACATGCACATTTTGTACA-3'(SEQ ID NO:8482)
KRAS-5164靶:5'-AAACATGCACATTTTGTACAT-3'(SEQ ID NO:8483)
KRAS-5167靶:5'-CATGCACATTTTGTACATTGT-3'(SEQ ID NO:8484)
KRAS-5168靶:5'-ATGCACATTTTGTACATTGTG-3'(SEQ ID NO:8485)
KRAS-5169靶:5'-TGCACATTTTGTACATTGTGC-3'(SEQ ID NO:8486)
KRAS-5170靶:5'-GCACATTTTGTACATTGTGCT-3'(SEQ ID NO:8487)
KRAS-5171靶:5'-CACATTTTGTACATTGTGCTT-3'(SEQ ID NO:8488)
KRAS-5172靶:5'-ACATTTTGTACATTGTGCTTT-3'(SEQ ID NO:8489)
KRAS-5173靶:5'-CATTTTGTACATTGTGCTTTC-3'(SEQ ID NO:8490)
KRAS-5197靶:5'-TGTGGGACATATGCAGTGTGA-3'(SEQ ID NO:8491)
KRAS-5198靶:5'-GTGGGACATATGCAGTGTGAT-3'(SEQ ID NO:8492)
KRAS-5199靶:5'-TGGGACATATGCAGTGTGATC-3'(SEQ ID NO:8493)
KRAS-5200靶:5'-GGGACATATGCAGTGTGATCC-3'(SEQ ID NO:8494)
KRAS-5201靶:5'-GGACATATGCAGTGTGATCCA-3'(SEQ ID NO:8495)
KRAS-5202靶:5'-GACATATGCAGTGTGATCCAG-3'(SEQ ID NO:8496)
KRAS-5203靶:5'-ACATATGCAGTGTGATCCAGT-3'(SEQ ID NO:8497)
KRAS-5204靶:5'-CATATGCAGTGTGATCCAGTT-3'(SEQ ID NO:8498)
KRAS-5205靶:5'-ATATGCAGTGTGATCCAGTTG-3'(SEQ ID NO:8499)
KRAS-5209靶:5'-GCAGTGTGATCCAGTTGTTTT-3'(SEQ ID NO:8500)
KRAS-5210靶:5'-CAGTGTGATCCAGTTGTTTTC-3'(SEQ ID NO:8501)
KRAS-5211靶:5'-AGTGTGATCCAGTTGTTTTCC-3'(SEQ ID NO:8502)
KRAS-5212靶:5'-GTGTGATCCAGTTGTTTTCCA-3'(SEQ ID NO:8503)
KRAS-5213靶:5'-TGTGATCCAGTTGTTTTCCAT-3'(SEQ ID NO:8504)
KRAS-5214靶:5'-GTGATCCAGTTGTTTTCCATC-3'(SEQ ID NO:8505)
KRAS-5234靶:5'-CATTTGGTTGCGCTGACCTAG-3'(SEQ ID NO:8506)
KRAS-5235靶:5'-ATTTGGTTGCGCTGACCTAGG-3'(SEQ ID NO:8507)
KRAS-5252靶:5'-TAGGAATGTTGGTCATATCAA-3'(SEQ ID NO:8508)
KRAS-5253靶:5'-AGGAATGTTGGTCATATCAAA-3'(SEQ ID NO:8509)
KRAS-5254靶:5'-GGAATGTTGGTCATATCAAAC-3'(SEQ ID NO:8510)
KRAS-5255靶:5'-GAATGTTGGTCATATCAAACA-3'(SEQ ID NO:8511)
KRAS-5256靶:5'-AATGTTGGTCATATCAAACAT-3'(SEQ ID NO:8512)
KRAS-5257靶:5'-ATGTTGGTCATATCAAACATT-3'(SEQ ID NO:8513)
KRAS-5258靶:5'-TGTTGGTCATATCAAACATTA-3'(SEQ ID NO:8514)
KRAS-5259靶:5'-GTTGGTCATATCAAACATTAA-3'(SEQ ID NO:8515)
KRAS-5260靶:5'-TTGGTCATATCAAACATTAAA-3'(SEQ ID NO:8516)
KRAS-5299靶:5'-TGAAATTAACTTTTAAATGTT-3'(SEQ ID NO:8517)
KRAS-5300靶:5'-GAAATTAACTTTTAAATGTTT-3'(SEQ ID NO:8518)
KRAS-5304靶:5'-TTAACTTTTAAATGTTTATAG-3'(SEQ ID NO:8519)
KRAS-5305靶:5'-TAACTTTTAAATGTTTATAGG-3'(SEQ ID NO:8520)
KRAS-5306靶:5'-AACTTTTAAATGTTTATAGGA-3'(SEQ ID NO:8521)
KRAS-5307靶:5'-ACTTTTAAATGTTTATAGGAG-3'(SEQ ID NO:8522)
KRAS-5308靶:5'-CTTTTAAATGTTTATAGGAGT-3'(SEQ ID NO:8523)
KRAS-5309靶:5'-TTTTAAATGTTTATAGGAGTA-3'(SEQ ID NO:8524)
KRAS-5347靶:5'-TAAAATTTGTAATATTTTTGT-3'(SEQ ID NO:8525)
KRAS-5348靶:5'-AAAATTTGTAATATTTTTGTC-3'(SEQ ID NO:8526)
KRAS-5349靶:5'-AAATTTGTAATATTTTTGTCA-3'(SEQ ID NO:8527)
KRAS-5350靶:5'-AATTTGTAATATTTTTGTCAT-3'(SEQ ID NO:8528)
KRAS-5351靶:5'-ATTTGTAATATTTTTGTCATG-3'(SEQ ID NO:8529)
KRAS-5352靶:5'-TTTGTAATATTTTTGTCATGA-3'(SEQ ID NO:8530)
KRAS-5353靶:5'-TTGTAATATTTTTGTCATGAA-3'(SEQ ID NO:8531)
KRAS-5354靶:5'-TGTAATATTTTTGTCATGAAC-3'(SEQ ID NO:8532)
KRAS-5389靶:5'-TTATTGTAATGTAATAAAAAT-3'(SEQ ID NO:8533)
KRAS-5390靶:5'-TATTGTAATGTAATAAAAATA-3'(SEQ ID NO:8534)
KRAS-5391靶:5'-ATTGTAATGTAATAAAAATAG-3'(SEQ ID NO:8535)
KRAS-5392靶:5'-TTGTAATGTAATAAAAATAGT-3'(SEQ ID NO:8536)
KRAS-5393靶:5'-TGTAATGTAATAAAAATAGTT-3'(SEQ ID NO:8537)
在上表2-7内,带下划线的残基指示2'-O-甲基残基,大写字母指示核糖核苷酸,小写字母表示脱氧核糖核苷酸,并且在表2中,“P-”指示5'-末端磷酸基。上面表3-6的DsiRNA试剂是具有平端的25/27mer试剂。表3-6的结构和/或修饰模式可以容易地适应于上述一般序列结构,例如第二条链的3'突出可延伸或收缩,第二条链的2'-O-甲基化可朝向第二条链5'端扩展,任选处于交替位点等。这种其它修饰是任选的,因为具有这种修饰的25/27mer DsiRNA也可以由上述DsiRNA试剂容易地设计出来,同时预期其为KRAS表达的功能性抑制剂。
在某些实施方案中,本发明的DsiRNA试剂需要第一条链的例如至少19、至少20、至少21、至少22、至少23、至少24、至少25或至少26个残基与第二条链的相应残基互补。在某些相关实施方案中,与第二条链的相应残基互补的这些第一条链残基任选为连续残基。
本文中使用的“DsiRNAmm”是指具有“错配容忍区(mismatch tolerant region)”的DisRNA,该“错配容忍区”含有由DsiRNA的有义链和反义链形成的双链体的一个、两个、三个或四个错配碱基对,其中这些错配都位于DsiRNA内处于DsiRNA任一端两个末端碱基对之间(并因此不包括DsiRNA任一端的两个末端碱基对)的位置处。错配碱基对位于“错配容忍区”内,该错配容忍区在本文中是关于相应靶核酸的预计的Ago2切割位点的位置而定义。错配容忍区位于靶链的预计的Ago2切割位点的“上游”。在这种情形中,“上游”应理解为DsiRNAmm双链体的最靠近5’的部分,其中5’是指DsiRNA双链体的有义链的定向。因此,错配容忍区位于有义链(过客链)上对应于靶核酸的预计的Ago2切割位点的碱基的上游(参看图1);或者,当提到DsiRNAmm的反义链(引导链)时,错配容忍区也可以描述为位于与靶核酸的预计的Ago2切割位点互补的碱基下游,也就是说,DsiRNAmm反义链的最靠近3’的部分(其中反义链的1位是反义链的5’末端核苷酸,参看图1)。
在一个实施方案中,例如用图1中所示的编号,当从双链体有义链的5’端开始的核苷酸编号时,错配容忍区位于碱基对3-9之间且包括碱基对3-9。因此,本发明的DsiRNAmm在右手延伸的DsiRNA的有义链的3、4、5、6、7、8或9位中任一位置具有单一错配碱基对(其中1位是有义链5’末端的核苷酸,且9位是紧邻对应于有义链序列的靶KRAS RNA序列预计的Ago2切割位点5’的有义链核苷酸残基)。在某些实施方案中,对于在有义链3、4、5、6、7、8或9位中任一位置具有错配碱基对核苷酸的DsiRNAmm,反义链的相应错配碱基对核苷酸不仅与DsiRNAmm有义链序列形成错配碱基对,而且还与DsiRNAmm靶KRAS RNA序列形成错配碱基对(因此,在DsiRNAmm内的错配碱基对处,反义链序列与有义链序列之间的互补性受到破坏,并且DsiRNAmm反义链序列与靶KRAS RNA序列之间的互补性也同样受到破坏)。在替代的实施方案中,DsiRNAmm反义链的错配碱基对核苷酸只与DsiRNAmm有义链序列的相应核苷酸形成错配碱基对,而与其相应靶KRAS RNA序列核苷酸碱基配对(因此,在DsiRNAmm内的错配碱基对处,反义链序列与有义链序列之间的互补性受到破坏,但DsiRNAmm反义链序列与靶KRAS RNA序列之间的互补性仍然保持)。
如上文所述在错配容忍区(错配区)内具有单一错配碱基对的本发明DsiRNAmm(例如,在有义链3、4、5、6、7、8或9位中任一位置带有错配核苷酸残基的DsiRNAmm)还可包括一个、两个或甚至三个另外的错配碱基对。在优选实施方案中,DsiRNAmm中的这一个、两个或三个另外的错配碱基对出现在有义链的3、4、5、6、7、8和/或9位(以及反义链的相应残基处)。在DsiRNAmm内存在一个另外的错配碱基对的一个实施方案中,有义链两个错配碱基对可出现在例如有义链4位和6位核苷酸处(且错配也可以出现在反义链的相应核苷酸残基处)。
在具有两个错配碱基对的DsiRNAmm试剂中,错配可连续出现(例如,在沿着有义链核苷酸序列的连续位置处)。或者,有义链中与反义链序列形成错配碱基对的核苷酸可间杂有与反义链序列碱基配对的核苷酸(例如,对于在3位和6位具有错配核苷酸但在4位和5位不具有错配核苷酸的DsiRNAmm,有义链3位和6位的错配残基间杂有与反义链相应残基形成相配的碱基对的两个核苷酸)。例如,有义链中与相应反义链序列形成错配碱基对的两个残基(位于有义链的错配容忍区内)可与位于这些错配碱基对之间的0、1、2、3、4或5个相配的碱基对一起出现。
对于具有3个错配碱基对的某些DsiRNAmm试剂,错配可连续出现(例如,沿着有义链核苷酸序列以三个一组)。或者,有义链中与反义链序列形成错配碱基对的核苷酸可间杂有与反义链序列形成相配碱基对的核苷酸(例如,对于在3、4和8位具有错配核苷酸但在5、6和7位不具有错配核苷酸的DsiRNAmm,有义链3位和4位的错配残基彼此相邻,而有义链4位和8位的错配残基间杂有三个与反义链相应残基形成相配碱基对的核苷酸)。例如,有义链中与相应反义链序列形成错配碱基对的三个残基(位于有义链的错配容忍区内)可与位于这些错配碱基对任意两个间的0、1、2、3或4个相配的碱基对一起出现。
对于具有4个错配碱基对的某些DsiRNAmm试剂,错配可连续出现(例如,沿有义链核苷酸序列以四个一组)。或者,有义链中与反义链序列形成错配碱基对的核苷酸可间杂友与反义链序列形成相配碱基对的核苷酸(例如,对于在3、5、7和8位具有错配核苷酸但在4位和6位不具有错配核苷酸的DsiRNAmm,有义链7位与8位的错残基彼此相邻,而有义链3位和5位的错配碱基间杂有一个与反义链的相应残基形成相配碱基对的核苷酸,类似地,有义链5位和7位的错配残基也间杂有一个与反义链相应残基形成相配碱基对的核苷酸)。例如,有义链中与相应反义链序列形成错配碱基对的四个残基(位于有义链的错配容忍区内)可与位于这些错配碱基对的任意两个间的0、1、2或3个相配的碱基对一起出现。
在另一实施方案中,例如也用图1中所示的编号,本发明的DsiRNAmm包含错配容忍区,该错配容忍区在DsiRNA反义链的17、18、19、20、21、22或23位中任一者处具有单一错配碱基对核苷酸(其中1位是反义链5’末端核苷酸,且17位是紧邻与反义链序列充分互补的靶KRAS RNA序列的预计的Ago2切割位点的反义链3’(下游)的反义链核苷酸残基)。在某些实施方案中,对于相对于DsiRNAmm的有义链在反义链17、18、19、20、21、22或23位中任一者处具有错配碱基对核苷酸的DsiRNAmm,反义链的错配碱基对核苷酸不仅与DsiRNAmm有义链序列形成错配碱基对,而且还与DsiRNAmm靶KRAS RNA序列形成错配碱基对(因此,在DsiRNAmm内的错配碱基对处,反义链序列与有义链序列之间的互补性受到破坏,并且DsiRNAmm反义链序列与靶KRAS RNA序列之间的互补性也同样受到破坏)。在替代的实施方案中,DsiRNAmm反义链的错配碱基对核苷酸只与DsiRNAmm有义链序列的相应核苷酸形成错配碱基对,而与其相应靶KRAS RNA序列核苷酸碱基配对(因此,在DsiRNAmm内的错配碱基对处,反义链序列与有义链序列之间的互补性受到破坏,但DsiRNAmm反义链序列与靶KRASRNA序列之间的互补性仍然保持)。
如上文所述在错配容忍区内具有单一错配碱基对的本发明DsiRNAmm(例如,在反义链的17、18、19、20、21、22或23位处带有错配核苷酸残基的DsiRNAmm)还可包括一个、两个或甚至三个另外的错配碱基对。在优选实施方案中,DsiRNAmm的这一个、两个或三个另外的错配碱基对出现在反义链的17、18、19、20、21、22和/或23位(以及有义链的相应残基处)。在DsiRNAmm内存在一个另外的错配碱基对的一个实施方案中,反义链的两个错配碱基对可出现在例如反义链18位和20位的核苷酸处(且错配也出现在有义链的相应核苷酸残基处)。
在具有两个错配碱基对的DsiRNAmm试剂中,错配可连续出现(例如,在沿着反义链核苷酸序列的连续位置处)。或者,反义链中与有义链序列形成错配碱基对的核苷酸可间杂有与有义链序列碱基配对的核苷酸(例如,对于在17位和20位具有错配核苷酸但在18位和19位不具有错配核苷酸的DsiRNAmm,反义链17位和20位的错配残基间杂有与有义链相应残基形成相配的碱基对的两个核苷酸)。例如,反义链中与相应有义链序列形成错配碱基对的两个残基(位于有义链错配容忍区内)可与位于这些错配碱基对间的0、1、2、3、4、5或6个相配的碱基对一起出现。
对于具有3个错配碱基对的某些DsiRNAmm试剂,错配可连续发生(例如,沿着反义链核苷酸序列以三个一组)。或者,反义链中与有义链序列形成错配碱基对的核苷酸可间杂有与有义链序列形成相配碱基对的核苷酸(例如,对于在17、18和22位具有错配核苷酸但在19、20和21位不具有错配核苷酸的DsiRNAmm,反义链17位和18位的错配残基彼此相邻,而反义链18位和122位的错配残基间杂有三个与有义链相应残基形成相配碱基对的核苷酸)。例如,反义链与相应有义链序列形成错配碱基对的三个残基(位于反义链错配容忍区内)可与位于这些错配碱基对任意两个间的0、1、2、3、4、5或6个相配的碱基对一起出现。
对于具有4个错配碱基对的某些DsiRNAmm试剂,错配可连续发生(例如,沿着反义链核苷酸序列以四个一组)。或者,反义链中与有义链序列形成错配碱基对的核苷酸可间杂有与有义链序列形成相配碱基对的核苷酸(例如,对于在18、20、22和23位具有错配核苷酸但在19位和21位不具有错配核苷酸的DsiRNAmm,反义链22位和23位的错配残基彼此相邻,而反义链18位和20位的错配残基间杂有一个与有义链相应残基形成相配碱基对的核苷酸,类似地,反义链20位和22位的错配碱基也间杂有一个与有义链相应残基形成相配碱基对的核苷酸)。例如,反义链与相应有义链序列形成错配碱基对的四个残基(位于反义链的错配容忍区内)可与位于这些错配碱基对的任意两个间的0、1、2、3、4或5个相配的碱基对一起出现。
为清楚起见,上述DsiRNAmm试剂内错配核苷酸残基的位置都是根据DsiRNAmm有义链或反义链的5’末端残基编号。位于反义链错配容忍区(错配区)内的位置的编号可在有义链或反义链的5’末端附近向预计的Ago2裂解位点移位而且有变化。由此,反义链或有义链内优选的错配位点的位置也可以鉴别为这些错配向预计的Ago2切割位点的容许的接近。因此,在一个优选实施方案中,DsiRNAmm有义链中错配核苷酸的位置是有义链中紧邻相应靶KRAS RNA序列的预计的Ago2裂解位点的5’端(上游)的核苷酸残基。在其它优选实施方案中,DsiRNAmm有义链中的错配核苷酸位于有义链的核苷酸残基处,该核苷酸残基距预计的Ago2裂解位点5’端(上游)两个核苷酸、距预计的Ago2裂解位点5’端(上游)三个核苷酸、距预计的Ago2裂解位点5’端(上游)四个核苷酸、距预计的Ago2裂解位点5’端(上游)五个核苷酸、距预计的Ago2裂解位点5’端(上游)六个核苷酸、距预计的Ago2裂解位点5’端(上游)七个核苷酸、距预计的Ago2裂解位点5’端(上游)八个核苷酸或距预计的Ago2裂解位点5’端(上游)九个核苷酸。
示例性含单一错配的25/27mer DsiRNA(DsiRNAmm)包括以下结构(这些含错配的结构也可并入本文所示其它示例性DsiRNA结构中)。
5′-pXXMXXXXXXXXXXXXXXXXXXXXDD-3′
3′-XXXXMXXXXXXXXXXXXXXXXXXXXXXp-5’
5′-pXXXMXXXXXXXXXXXXXXXXXXXDD-3′
3′-XXXXXMXXXXXXXXXXXXXXXXXXXXXp-5’
5′-pXXXXMXXXXXXXXXXXXXXXXXXDD-3′
3′-XXXXXXMXXXXXXXXXXXXXXXXXXXXp-5’
5′-pXXXXXMXXXXXXXXXXXXXXXXXDD-3′
3′-XXXXXXXMXXXXXXXXXXXXXXXXXXXp-5'
5′-pXXXXXXMXXXXXXXXXXXXXXXXDD-3′
3′-XXXXXXXXMXXXXXXXXXXXXXXXXXXp-5’
3′-XXXXXXXXXMXXXXXXXXXXXXXXXXXp-5’
5′-pXXXXXXXXMXXXXXXXXXXXXXXDD-3′
3′-XXXXXXXXXXMXXXXXXXXXXXXXXXXp-5’
其中“X”=RNA,“D”=DNA,“p”=磷酸基,“M”=当链退火时不与另一互补链的相应“M”残基碱基配对(形成氢键)的核酸残基(RNA、DNA或非天然或经过修饰的核酸)。此类试剂的任何残基可任选为2’-O-甲基RNA单体–如以上所示从下(第二)链的3’-末端残基开始的2'-O-甲基RNA单体的交替定位也可用于上述DsiRNAmm试剂中。对于上述错配结构,上链是有义链,且下链是反义链。
在某些实施方案中,本发明的DsiRNA可含有错配,这些错配根据靶KRAS RNA序列存在,但未必以DsiRNA两条链内的错配碱基对存在–因此,DsiRNA可在DsiRNA第一条链与第二条链之间具有完全的互补性,但根据靶KRAS RNA仍具有错配残基(在某些实施方案中,这一情形有利于促进作用的功效和/或效力和/或持续时间)。在反义链与靶KRAS RNA序列之间出现错配的某些实施方案中,错配的位置在反义链内位于对应于靶区中预计的Ago2切割位点的5'的有义链序列的位置处–例如,位于反义链内与靶序列中预计的Ago2切割位点互补的反义链残基3’的反义链残基。
根据靶序列带有单一错配残基的示例性25/27mer DsiRNA包括以下优选结构。
其中“X”=RNA,“D”=DNA,“p”=磷酸基,“E”=当链退火时不与另一互补(靶)链的相应“A”RNA残基碱基配对(形成氢键)的核酸残基(RNA、DNA或非天然的或经过修饰的核酸),但这些核酸残基任选地与相应“B”残基(“B”残基也是RNA、DNA或非天然的或经过修饰的核酸)碱基配对。此类试剂的任何残基可任选为2’-O-甲基RNA单体–如以上所示,从下(第二)链的3’-末端残基开始,2'-O-甲基RNA单体的交替定位也可用于上述DsiRNA试剂中。
除上述示例性结构外,本发明的DsiRNA还可具有一个、两个或三个另外与靶KRASRNA序列形成错配的其它残基。这些错配可以是连续的,或者可以间杂有与靶KRAS RNA序列形成相配的碱基对的核苷酸。在间杂有形成相配的碱基对的核苷酸的情况中,那么错配残基可以在单链内彼此分隔开,在这些形成错配的残基之间间隔1、2、3、4、5、6、7或甚至8个碱基配对的核苷酸。
就上述DsiRNAmm试剂来说,对于在DsiRNA内与靶KRAS RNA序列形成错配碱基对(但可能与或可能不与相应有义链核苷酸形成错配)的反义链核苷酸的优选位置是在反义链区内,该区域处于与DsiRNA的预计的Ago2切割位点互补的反义链序列的3’端(下游)(例如,在图1中,在预计的Ago2切割位点的3’端的反义链区域是形成错配的残基所优选的,并且恰巧是位于图1中所示25/27mer试剂反义链的17-23位处)。因此,在一个优选的实施方案中,DsiRNAmm反义链中错配核苷酸的位置(相对于靶KRAS RNA序列)是紧邻相应靶KRAS RNA序列中预计的Ago2裂解位点的反义链序列内3’端(下游)的反义链核苷酸残基。在其它优选实施方案中,DsiRNAmm反义链中的错配核苷酸(相对于靶KRAS RNA序列)位于反义链的核苷酸残基处,该核苷酸残基距相应预计的Ago2裂解位点3’端(下游)两个核苷酸、距相应预计的Ago2裂解位点3’端(下游)三个核苷酸、距相应预计的Ago2裂解位点3’端(下游)四个核苷酸、距相应预计的Ago2裂解位点3’端(下游)五个核苷酸、距相应预计的Ago2裂解位点3’端(下游)六个核苷酸、距相应预计的Ago2裂解位点3’端(下游)七个核苷酸、距相应预计的Ago2裂解位点3’端(下游)八个核苷酸或距相应预计的Ago2裂解位点3’端(下游)九个核苷酸。
在反义链具有两个形成错配的核苷酸(其中形成错配的核苷酸相对于靶KRASRNA序列是形成错配的)的DsiRNA试剂中,错配可连续出现(例如,在沿着反义链核苷酸序列的连续位置)。或者,反义链中与靶KRAS RNA序列形成错配碱基对的核苷酸可间杂有与靶KRAS RNA序列碱基配对的核苷酸(例如,对于在17位和20位(在如图1所示从25/27mer试剂反义链的从5’末端(1位)开始)具有形成错配的核苷酸但在18位和19位不具有形成错配的核苷酸的DsiRNA,有义链17位和20位的错配残基间杂有两个与靶KRAS RNA序列相应残基形成相配的碱基对的核苷酸)。例如,反义链与相应靶KRAS RNA序列形成错配碱基对的两个残基(位于反义链错配容忍区内)可与位于这些形成错配的碱基对间的0、1、2、3、4或5个相配的碱基对(关于靶KRAS RNA序列)一起存在。
对具有3个形成错配的碱基对(关于靶KRAS RNA序列为错配形成的)的某些DsiRNA,形成错配的核苷酸可连续出现(例如,沿着反义链核苷酸序列以三个一组)。或者,反义链中与靶KRAS RNA序列形成错配碱基对的核苷酸可间杂有与靶KRAS RNA序列形成相配碱基对的核苷酸(例如,对于在17、18和22位具有错配核苷酸,但在19、20和21位不具有错配核苷酸的DsiRNA,反义链17位和18位的形成错配的残基彼此相邻,而反义链18位和22位的形成错配的残基间杂有三个与靶KRAS RNA序列的相应残基形成相配的碱基对的核苷酸)。例如,反义链与相应靶KRAS RNA序列形成错配碱基对的三个残基(位于反义链错配容忍区内)可与位于这些形成错配的碱基对中任意两个间的0、1、2、3或4个相配的碱基对一起出现。
对于有4个形成错配的碱基对(关于靶KRAS RNA序列为错配形成的)的某些DsiRNA,形成错配的核苷酸可连续出现(例如,沿着有义链核苷酸序列以四个一组)。或者,反义链中与靶KRAS RNA序列形成错配碱基对的核苷酸可间杂有与靶KRAS RNA序列形成相配的碱基对的核苷酸(例如,对于在17、19、21和22位具有形成错配的核苷酸,但在18位和20位不具有形成错配的核苷酸的DsiRNA,反义链21位和22位的形成错配的残基彼此相邻,而反义链17位和19位的形成错配的残基间杂有一个与靶KRAS RNA序列的相应残基形成相配的碱基对的核苷酸,类似地,反义链19位和21位的形成错配的残基也间杂有一个与靶KRASRNA序列的相应残基形成相配的碱基对的核苷酸)。例如,与相应靶KRAS RNA序列形成错配碱基对的四个残基(位于反义链错配容忍区内)可与位于这些形成错配的碱基对中任意两个间的0、1、2或3个相配的碱基对一起出现。
以上描述了DsiRNAmm和其它DsiRNA结构,以便示例说明DsiRNAmm和DsiRNA试剂的某些结构。可使以上DsiRNAmm和DsiRNA结构适于以产生例如以下所示其它DsiRNA结构的DsiRNAmm形式。如上文示例说明的,DsiRNAs也可以设计成在DsiRNA的反义链与靶序列间具有单一错配(或两个、三个或四个错配),但是任选能在DsiRNA的有义链与反义链序列之间保持完全的互补性。
还应注意,以下示例说明的DsiRNA试剂也可在其双链和/或靶KRAS RNA比对结构内具有插入/缺失(in/del)结构。因此,本发明的DsiRNA可设计成在例如与靶KRAS RNA序列相比较的反义链序列和/或与有义链序列相比较的反义链序列中具有in/del变异,其中用于放置这些in/del核苷酸的优选位置对应于上述用于放置错配和/或形成错配的碱基对的那些位置。
也应注意,本发明的DsiRNA可容忍在有义链3’-末端区域/反义链5’-末端区域内的错配,因为这一区域经模拟以被Dicer加工并从装载到RISC中的引导链序列中释放。带有这种错配的本发明示例性的DsiRNA结构包括下述:
其中“X”=RNA,“D”=DNA,“p”=磷酸基,“I”和“J”=相互不能碱基对(形成氢键)的核酸残基(RNA、DNA或非天然或经过修饰的核酸),但任选“J”与靶RNA序列核苷酸“H”互补。此类试剂的任何残基可任选为2’-O-甲基RNA单体–从下(第二)链的3’-末端残基开始的2'-O-甲基RNA单体的交替定位–或上述任何甲基化模式–也可用于上述DsiRNA试剂中。上述错配也可以在本发明的DsiRNA内组合。
在以下结构中,将这些错配引入不对称KRAS-420DsiRNA内(新引入的错配残基以斜体字表示):
KRAS-42025/27mer DsiRNA,错配位置=有义链22位(从5’-末端开始)
5′-GUAUUUGCCAUAAAUAAUACUCAat-3′(SEQ ID NO:5136)
3′-CACAUAAACGGUAUUUAUUAUGAUUUA-5′(SEQ ID NO:26)
任选地,有义链22位的错配“C”残基是“G”或“U”。
KRAS-42025/27mer DsiRNA,错配位置=有义链23位
5′-GUAUUUGCCAUAAAUAAUACUACat-3′(SEQ ID NO:5137)
3′-CACAUAAACGGUAUUUAUUAUGAUUUA-5′(SEQ ID NO:26)
任选地,有义链23位的错配“C”残基是“G”或“U”。
KRAS-42025/27mer DsiRNA,错配位置=有义链24位
5′-GUAUUUGCCAUAAAUAAUACUAACt-3′(SEQ ID NO:5138)
3′-CACAUAAACGGUAUUUAUUAUGAUUUA-5’(SEQ ID NO:26)
任选地,有义链24位的错配“c”残基是“g”或“t”。
KRAS-42025/27mer DsiRNA,错配位置=有义链25位
5′-GUAUUUGCCAUAAAUAAUACUAAag-3′(SEQ ID NO:5139)
3′-CACAUAAACGGUAUUUAUUAUGAUUUA-5′(SEQ ID NO:26)
任选地,有义链25位的错配“g”残基是“c”或“a”。
KRAS-42025/27mer DsiRNA,错配位置=反义链1位
5′-GUAUUUGCCAUAAAUAAUACUAAat-3′(SEQ ID NO:105)
3′-CACAUAAACGGUAUUUAUUAUGAUUUC-5′(SEQ ID NO:5140)
任选地,反义链1位的错配“C”残基是“G”或“U”。
KRAS-42025/27mer DsiRNA,错配位置=反义链2位
5′-GUAUUUGCCAUAAAUAAUACUAAat-3′(SEQ ID NO:105)
3′-CACAUAAACGGUAUUUAUUAUGAUUCA-5′(SEQ ID NO:5141)
任选地,反义链2位的错配“C”残基是“G”或“A”。
KRAS-42025/27mer DsiRNA,错配位置=反义链3位
5′-GUAUUUGCCAUAAAUAAUACUAAat-3′(SEQ ID NO:105)
3′-CACAUAAACGGUAUUUAUUAUGAUGUA-5′(SEQ ID NO:5142)
任选地,反义链3位的错配“G”残基是“A”或“C”。
KRAS-42025/27mer DsiRNA,错配位置=反义链4位
5′-GUAUUUGCCAUAAAUAAUACUAAat-3′(SEQ ID NO:105)
任选地,反义链4位的错配“G”残基是“A”或“C”。
如上文所述,可以在本文所述任何DsiRNA上引入这些错配。
可将这些DsiRNA结构的错配组合以产生在有义链3’末端四个核苷酸/反义链5’末端四个核苷酸内具有例如2、3或甚至4个错配的DsiRNA。
事实上,鉴于可在有义链3’-末端残基/反义链5’-末端残基处并入DsiRNA中的序列的灵活性,在某些实施方案中,本发明的不对称DsiRNA的序列要求可以表示为下述(极简单)结构(如对于示例性KRAS-420DsiRNA序列所示):
5′-GUAUUUGCCAUAAAUAAUACUXXX[X]n-3′(SEQ ID NO:6839)
3′-CACAUAAACGGUAUUUAUUAUXXXXX[X]n-5′(SEQ ID NO:6840)
其中n=1至5、1至10、1至20、1至30、1至50或者1至80或更多。
KRAS-420靶:5’-GTGTATTTGCCATAAATAATAXXXXXX-3’(SEQ ID NO:6841)
KRAS靶区(target sight)也可以是由互补靶位点与指定靶位点重叠的数个寡核苷酸中一者或多者所靶向的位点。例如,对于示例性KRAS-420DsiRNA,注意到,靶向重叠且仅略微偏移的KRAS序列的某些DsiRNA可以表现与KRAS-420类似的活性水平(具体说来,参看图10的KRAS-415、KRAS-417和KRAS-418DsiRNA,以及表9和图12和图13的KRAS-422、KRAS-423、KRAS-424、KRAS-425和KRAS-426DsiRNA)。因此,在某些实施方案中,具有大量重叠序列的一系列DsiRNA可有效靶向指定的靶序列区。(例如,如果考虑KRAS-420位点周围的DsiRNA,那么更加包容的KRAS靶序列可列举为,如例如5'-TCTTTGTGTATTTGCCATAAATAATACTAAATCA-3'(SEQ ID NO:6842),其中任一给定的DsiRNA(例如,选自KRAS-415、KRAS-417、KRAS-418、KRAS-420、KRAS-422、KRAS-423、KRAS-424、KRAS-425和KRAS-426的DsiRNA)只靶向所述序列区内的子序列,而整个序列可视为这一系列DsiRNA的活性靶)。
另外和/或或者,如上文所述,有义链3’末端四个核苷酸/反义链5’末端四个核苷酸内的错配可与位于其它错配容忍位置的错配组合。
鉴于本发明将上述Dicer底物试剂(DsiRNA)鉴别为通过靶向特定KRAS序列抑制KRAS水平的抑制剂,也应认识到,还可以合成具有与本文所述类似结构的DsiRNA,这些DsiRNA靶向SEQ ID NO:1或SEQ ID NO:3的KRAS序列或者其变体内的其它序列(例如,与SEQID NO:1和/或SEQ ID NO:3序列具有80%同一性、90%同一性、95%同一性、96%同一性、97%同一性、98%同一性、99%或更高同一性的靶序列)。
抗KRAS DsiRNA的设计/合成
根据经验已发现,与19-23mer siRNA试剂相比较,25至35个核苷酸且尤其是25至30个核苷酸的较长dsRNA种类(DsiRNA)在效力和作用持续时间方面产生意外有效的结果。不希望受dsRNA加工机制的基础理论的束缚,认为较长的dsRNA种类可用作细胞的细胞质中Dicer酶的底物。Dicer除了将本发明的dsRNA裂解成较短的片段外,还被认为有助于将源自于裂解的dsRNA的单链裂解产物并入RISC复合物中,该RISC复合物负责破坏靶基因KRAS(或与KRAS相关疾病或病症有关的其它基因)或源自于靶基因KRAS的细胞质RNA(例如,KRASRNA)。先前的研究(Rossi等,美国专利申请No.2007/0265220)已经证实,Dicer对dsRNA种类(具体说来,DsiRNA试剂)的可裂解性与dsRNA种类的效力和作用持续时间增加相应。
某些优选的抗KRAS DsiRNA试剂选自预先筛选的群。DsiRNA的设计可任选地涉及使用预测评分算法,这些算法执行跨序列区域的许多可能DsiRNA试剂的预计活性/功效的计算机(in silico)评估。有关这些评分算法的设计的信息参见例如Gong等(BMCBIOINFORMATICS2006,7:516),虽然近期的“v3”算法提出一种在理论上相对于本领域中先前可用的siRNA评分算法有所改进的算法。(“v3”评分算法是一种机器学习算法,该算法不依靠于人类序列的任何偏好。此外,“v3”算法衍生自数据集,该数据集是衍生得到Gong等所述的老的“v2”算法的数据集的约3倍。)
本发明DsiRNA试剂的第一与第二寡核苷酸不需要完全互补。事实上,在一个实施方案中,有义链的3'-末端含有一个或多个错配。一方面,两个错配被并入有义链3'末端处。在另一实施方案中,本发明的DsiRNA是含有两个RNA寡核苷酸的双链RNA分子,其中每个RNA寡核苷酸的长度为27个核苷酸,并且当彼此退火时具有平端并且在有义链3'末端(反义链5'末端)上具有两个核苷酸错配。已经提出,使用错配或降低热动力学稳定性(具体说来,在3'-有义链/5'-反义链位置处)可能通过影响与siRNA进入RISC一起发生的一些限速解链步骤来促进或便利反义链进入RISC(Schwarz等,2003,Cell115:199-208;Khvorova等,2003,Cell115:209-216)。因此,末端碱基组合物已经被包括在供选择活性21mer siRNA双链体的设计算法中(Ui-Tei等,2004,Nucleic Acids Res32:936-948;Reynolds等,2004,NatBiotechnol22:326-330)。通过用Dicer裂解本实施方案的dsRNA,含有错配的小端-末端序列将保持与反义链不配对(变为3'-突出的一部分)或从最终21-mer siRNA中完全裂解。因此,这些“错配”不是以错配形式保留在RISC的最终RNA组分中。在Dicer底物有义链3'端的片段的碱基错配或不稳定可能通过促进由Dicer加工来提高RNAi中合成双链体的效力的发现,是过去描述25-30mer dsRNA(本文中又称“DsiRNAs”;Rossi等,美国专利申请No.2005/0277610、No.2005/0244858和No.2007/0265220)的设计和使用的工作的一项意外发现。
抗KRAS DsiRNA的修饰
抑制双链RNA(“dsRNAs”)作用的一个主要因素是核酸酶对dsRNA(例如,siRNA和DsiRNA)的降解。3'-外切核酸酶是血清中存在的主要核酸酶活性,而且修饰反义DNA寡核苷酸的3'-端对于防止降解至关重要(Eder等,1991,Antisense Res Dev,1:141-151)。已经鉴别出称为ERI-1的RNase-T家族核酸酶,该核酸酶具有涉及siRNA的调控和降解的3'到5'外切核酸酶活性(Kennedy等,2004,Nature427:645-649;Hong等,2005,Biochem J,390:675-679)。这一基因在小鼠中又称为Thex1(NM_02067)或在人中称为THEX1(NM_153332),并且涉及组蛋白mRNA的降解;它还介导siRNA中3'-突出的降解,但不会降解双链体RNA(Yang等,2006,J Biol Chem,281:30447-30454)。因此,可以预期dsRNA(包括本发明的DsiRNA)3'端稳定化将提高稳定性是合理的。
XRN1(NM_019001)是一种存在于P小体(P-body)中的5'到3'外切核酸酶,且涉及miRNA所靶向的mRNA的降解(Rehwinkel等,2005,RNA11:1640-1647),而且还能负责完成由siRNA引导的由内部裂解起始的降解。XRN2(NM_012255)是一种不同的5'到3'外切核酸酶,其涉及核RNA的加工。
RNase A是哺乳动物中一种主要的内切核酸酶活性,其降解RNA。它对ssRNA具有特异性,并且在嘧啶碱基的3'端裂解。在血清中孵育后,通过质谱法可检测到与RNase A裂解相符的siRNA降解产物(Turner等,2007,Mol Biosyst3:43-50)。3'-突出增强siRNA对RNase降解的敏感性。耗尽血清中的RNase A将减少siRNA的降解;这一降解确实显示出某种序列偏好,而且不太偏好在末端具有多聚A/U序列的序列(Haupenthal等,2006BiochemPharmacol71:702-710)。这表明双链体中稳定性较低的区域可“呼吸(breathe)”并提供可供RNase A降解的瞬时单链物质的可能性。可以将RNase A抑制剂加入血清中,并提高siRNA寿命和效力(Haupenthal等,2007,Int J.Cancer121:206-210)。
在21mer中,硫代磷酸或硼烷磷酸修饰直接使内部核苷磷酸键稳定。硼烷磷酸修饰的RNA具有较高核酸酶抗性,可有效作为沉默试剂,并且相对无毒。硼烷磷酸修饰的RNA不能使用标准化学合成方法制造,而是通过体外转录(IVT)制备(Hall等,2004,NucleicAcids Res32:5991-6000;Hall等,2006,Nucleic Acids Res34:2773-2781)。硫代磷酸(PS)修饰易于放在RNA双链体中任何所需的位置,并且可以使用标准化学合成方法制备。PS修饰显示出剂量依赖性毒性,因此大多数研究人员推荐在siRNA中限量并入,偏向于3'端,其中在3'端防止受到核酸酶影响是最重要的(Harborth等,2003,Antisense Nucleic AcidsDrug Dev13:83-105;Chiu和Rana,2003,Mol Cell10:549-561;Braasch等,2003,Biochemistry42:7967-7975;Amarzguioui等,2003,Nucleic Acids Research31:589-595)。更广泛的PS修饰可与有效RNAi活性相容;然而,使用糖修饰(例如2'-O-甲基RNA)可能是较优的(Choung等,2006,Biochem Biophys Res Commun342:919-927)。
多种取代可位于核糖2'位处,此处的取代一般会增加双链体稳定性(Tm),并且可极大地提高核酸酶抗性。2'-O-甲基RNA是哺乳动物核糖体RNA和转运RNA中所见的天然修饰。已知siRNA中的2'-O-甲基修饰,但双链体内经过修饰的碱基的确切位置对于保持效力极为重要,并且用2'-O-甲基RNA完全取代RNA将使siRNA失活。例如,采用交替2'-O-甲基碱基的模式的效力可与未修饰的RNA相当,并且在血清中非常稳定(Choung等,2006,BiochemBiophys Res Commun342:919-927;Czauderna等,2003,Nucleic Acids Research31:2705-2716)。
2'-氟(2'-F)修饰也与dsRNA(例如siRNA和DsiRNA)的功能相容;这种修饰最常置于嘧啶位点(归因于试剂成本和可用性),并且能与嘌呤位置处的2'-O-甲基修饰组合;2'-F嘌呤是可利用的,并且也可以使用。此类经过大量修饰的双链体在体外可以是RNAi的有效触发剂(Allerson等,2005,J Med Chem48:901-904;Prakash等,2005,J Med Chem48:4247-4253;Kraynack和Baker,2006,RNA12:163-176),并且当在体内使用时可提高性能并延长作用持续时间(Morrissey等,2005,Hepatology41:1349-1356;Morrissey等,2005,NatBiotechnol23:1002-1007)。Allerson教导了一种包含替代性2'-F和2'-O-Me碱基的特别有效的核酸酶稳定的平端19mer双链体。在这种设计中,交替2'-O-Me残基以与Czauderna所采用的模式相同的模式定位,但其余RNA残基被转化成2'-F修饰的碱基。Morrissey所采用的特别有效的核酸酶抗性siRNA采用一种在体内特别有效的核酸酶抗性siRNA。除2'-O-MeRNA和2'-F RNA外,此双链体还包括DNA、RNA、倒转无碱基残基和3'末端PS内部核苷键。尽管广泛修饰具有某些益处,但双链体的更有限的修饰也可以提高体内性能,而且更简单且制造成本较低。Soutschek等(2004,Nature432:173-178)在体内采用一种双链体,并且主要是具有两个2'-O-Me RNA碱基和限制性3'-末端PS内部核苷键的RNA。
锁核酸(LNA)是一类不同的2'修饰,可用于使dsRNA(例如,siRNA和DsiRNA)稳定。保持效力的LNA并入模式比2'-O-甲基或2'-F碱基更具局限性,因此优选限制性修饰(Braasch等,2003,Biochemistry42:7967-7975;Grunweller等,2003,Nucleic AcidsRes31:3185-3193;Elmen等,2005,Nucleic Acids Res33:439-447)。即使是有限的并入,使用LNA修饰也能提高dsRNA的体内性能,而且还可改变或提高脱靶效应特征(Mook等,2007,Mol Cancer Ther6:833-843)。
引入细胞或活动物中的合成核酸可视为“外来的”,并能触发免疫响应。免疫刺激构成脱靶效应的一个主要类别,其可明显改变实验结果,甚至会导致细胞死亡。固有的免疫系统包括与介导这些反应的DNA和RNA特异性相互作用的受体分子集合,其中有一些位于细胞质中,而有一些则存在于核内体中(Marques和Williams,2005,Nat Biotechnol23:1399-1405;Schlee等,2006,Mol Ther14:463-470)。利用阳离子型脂质或脂质体递送siRNA会将siRNA暴露于细胞质和内体隔室,使触发体内和体外1型干扰素(IFN)反应的风险最大(Morrissey等,2005,Nat Biotechnol23:1002-1007;Sioud和Sorensen,2003,BiochemBiophys Res Commun312:1220-1225;Sioud,2005,J Mol Biol348:1079-1090;Ma等,2005,Biochem Biophys Res Commun330:755-759)。细胞内转录的RNA免疫源性较低(Robbins等,2006,Nat Biotechnol24:566-571),并且当使用基于脂质的方法递送时具有免疫源性的合成RNA在使用机械方式引入细胞中(甚至体内)时会避开免疫刺激(Heidel等,2004,NatBiotechnol22:1579-1582)。然而,基于脂质的递送方法很方便、有效并且被广泛使用。防止免疫响应的一些一般策略是必要的,尤其对于存在所有细胞类型,而且产生免疫响应的风险最高的体内应用来说。使用化学方式修饰的RNA可以解决大部分或甚至所有这些问题。
在某些实施方案中,修饰可包括在本发明的抗KRAS DsiRNA试剂中,只要这种修饰不会阻止DsiRNA试剂具有KRAS抑制活性即可。在一个实施方案中,可进行一种或多种修饰以增进DsiRNA试剂的Dicer加工(用于确定DsiRNA的Dicer加工的测定如上文所述)。在第二实施方案中,进行一种或多种修饰以引起更有效的KRAS抑制(如本文所述,DsiRNA的KRAS抑制/KRAS抑制活性可通过本领域公认的用于测定RNA水平的方法或用于测定Kras多肽水平的方法测定,这些水平的评估应代替或结合例如KRAS mRNA水平的评估)。在第三实施方案中,进行一种或多种修饰以支持更高的KRAS抑制活性(测定KRAS抑制活性的方式如上文所述)。在第四实施方案中,进行一种或多种修饰,使得欲递送到细胞中的每一DsiRNA试剂分子具有更高的KRAS抑制活性的效力(KRAS抑制活性的效力如上文所述)。可将修饰并入3'末端区域、5'末端区域、3'末端和5'末端区域,或在一些情况下并入序列内的各个位置。鉴于上文所述的限制,可将修饰的数量和组合并入DsiRNA试剂中。在存在多个修饰的情况下,这些修饰可以相同或不同。涵盖了碱基、糖部分、磷酸骨架和其组合的修饰。任一5'末端都可被磷酸化。
对于磷酸骨架预期的修饰的实例包括膦酸(包括甲基膦酸)、硫代磷酸和磷酸三酯修饰(例如烷基磷酸三酯)等。对于糖部分预期的修饰的实例包括2'-烷基嘧啶,例如2'-O-甲基、2'-氟,氨基和脱氧修饰等(参见例如,Amarzguioui等,2003,Nucleic AcidResearch31:589-595)。对于碱基预期的修饰的实例包括无碱基糖、2-O-烷基修饰的嘧啶、4-硫尿嘧啶、5-溴尿嘧啶、5-碘尿嘧啶和5-(3-氨基烯丙基)-尿嘧啶等。也可以并入锁核酸或LNA。已知许多其它修饰,并且这些修饰也可以使用,只要满足上述标准即可。修饰的实例也公开于美国专利Nos.5,684,143、5,858,988和6,291,438以及美国公开的专利申请No.2004/0203145A1中。其它修饰公开于Herdewijn(2000,Antisense Nucleic Acid DrugDev10:297-310);Eckstein(2000,Antisense Nucleic Acid Drug Dev10:117-21);Rusckowski等(2000,Antisense Nucleic Acid Drug Dev10:333-345);Stein等(2001,Antisense Nucleic Acid Drug Dev11:317-25);Vorobjev等(2001,Antisense NucleicAcid Drug Dev11:77-85)中。
所预期的一种或多种修饰可以并入任一链中。DsiRNA试剂中修饰的布置可极大地影响DsiRNA试剂的特性,包括赋予较高效力和稳定性、减小毒性、增强Dicer加工和使免疫响应减到最少。在一个实施方案中,反义链或有义链或者两条链具有一个或多个2'-O-甲基修饰的核苷酸。在另一实施方案中,反义链含有2'-O-甲基修饰的核苷酸。在另一实施方案中,反义链含有包含2'-O-甲基修饰的核苷酸的3'突出。反义链还可以包括其它2'-O-甲基修饰的核苷酸。
在本发明某些实施方案中,抗KRAS DsiRNA试剂具有以下一种或多种性质:(i)DsiRNA试剂是不对称的,例如在反义链上具有3'突出,以及(ii)DsiRNA试剂在有义链上具有经过修饰的3'端,以引导dsRNA的Dicer结合和加工而成为活性siRNA的定向。根据本实施方案,dsRNA中最长的链包含25-35个核苷酸(例如,25、26、27、28、29、30、31、32、33、34或35个核苷酸)。在某些此类实施方案中,DsiRNA试剂是不对称的,以致有义链包含25-34个核苷酸,且有义链的3’端与反义链的5’端形成平端,而反义链包含26-35个核苷酸,并在反义链3’端上形成突出。在一个实施方案中,DsiRNA试剂是不对称的,以致有义链包含25-28个核苷酸,且反义链包含25-30个核苷酸。因此,得到的dsRNA在反义链3'端上具有突出。该突出为1-4个核苷酸,例如2个核苷酸。有义链还可以具有5'磷酸。
在其它实施方案中,DsiRNA试剂的有义链被位于有义链3'端的适当修饰剂修饰,以便于Dicer加工,即,DsiRNA试剂被设计成引导Dicer结合和加工的定向。适合的修饰剂包括核苷酸,例如脱氧核糖核苷酸、双脱氧核糖核苷酸、无环核苷酸等,以及空间位阻分子,例如荧光分子等。无环核苷酸利用2-羟基乙氧基甲基取代dNMP中通常存在的2'-脱氧呋喃核糖基糖。其它核苷酸修饰剂可包括3'-脱氧腺苷(虫草素)、3'-叠氮基-3'-脱氧胸苷(AZT)、2',3'-双脱氧肌苷(ddI)、2',3'-双脱氧-3'-硫代胞苷(3TC)、2',3'-双脱氢-2',3'-双脱氧胸苷(d4T),以及3'-叠氮基-3'-脱氧胸苷(AZT)、2',3'-双脱氧-3'-硫代胞苷(3TC)和2',3'-双脱氢-2',3'-双脱氧胸苷(d4T)的单磷酸核苷酸。在一个实施方案中,使用脱氧核苷酸作为修饰剂。当利用核苷酸修饰剂时,用1-3个核苷酸修饰剂或2个核苷酸修饰剂取代有义链3'端上的核糖核苷酸。当利用空间位阻分子时,这些分子附接到反义链3'端的核糖核苷酸。因此,该链的长度不会随修饰剂的并入而改变。在另一实施方案中,本发明涵盖取代DsiRNA试剂中的两个DNA碱基,以引导反义链的Dicer加工的定向。在本发明另一实施方案中,用两个末端DNA碱基取代有义链3'端上的两个核糖核苷酸,从而在有义链3'端和反义链5'端上形成双链体的平端,并且两个核苷酸RNA突出位于反义链3'端上。这是一种在平端上具有DNA且在突出端上具有RNA碱基的不对称组合物。
本发明DsiRNA试剂的有义链与反义链是在生物条件(例如,细胞的细胞质中所见的条件)下退火。此外,DsiRNA试剂的一个序列区,尤其是反义链序列区的序列长度为至少19个核苷酸,其中这些核苷酸在邻近反义链3'端的21个核苷酸的区域中,并与由靶基因产生的RNA的核苷酸序列充分互补。
DsiRNA试剂还可以具有以下一种或多种其它性质:(a)反义链相对于典型21mer向右偏移(例如,DsiRNA包含延伸到DsiRNA内预计的Dicer裂解位点的5’端的一定长度的反义链核苷酸,且这些反义链核苷酸与延伸有义链中预计的Dicer裂解位点3’端的有义链的相应核苷酸碱基配对);(b)这些链可能不完全互补,即,这些链可能含有简单的错配碱基对(在某些实施方案中,本发明DsiRNA具有1、2、3、4或甚至5个或更多个错配碱基对,条件是具有错配碱基对的DsiRNA的KRAS抑制活性保持在充足水平(例如,与不具有错配碱基对的相应DsiRNA相比较,保持至少50%KRAS抑制活性或更高、至少60%KRAS抑制活性或更高、至少70%KRAS抑制活性或更高、至少80%KRAS抑制活性或更高、至少90%KRAS抑制活性或更高,或者至少95%KRAS抑制活性或更高。在某些实施方案中,错配碱基对存在于DsiRNA反义链与有义链之间。在一些实施方案中,错配碱基对存在于(或预期存在于)反义链与靶RNA之间。在某些实施方案中,反义链残基与靶RNA内位于预计的Ago2裂解位点的靶RNA序列中3’端的相应残基之间错配碱基对的存在保持并且可能甚至是增强本发明DsiRNA的KRAS抑制活性);以及(c)碱基修饰,例如锁核酸,可包括在有义链5'端中。“典型”的21mer siRNA是使用常规技术而设计的。在一种技术中,常常平行或在含有对同一靶具有特异性的几个不同siRNA双链体的库中测试多个位点,以期发现一种试剂是有效的(Ji等,2003,FEBS Lett552:247-252)。其它技术使用设计规则和算法以增加获得活性RNAi效应分子的可能性(Schwarz等,2003,Cell115:199-208;Khvorova等,2003,Cell115:209-216;Ui-Tei等,2004,NucleicAcid Res32:936-948;Reynolds等,2004,Nat Biotechnol22:326-330;Krol等,2004,JBiol Chem279:42230-42239;Yuan等,2004,Nucl Acids Res32(Webserver issue):W130-134;Boese等,2005,Methods Enzymol392:73-96)。也已经开发出siRNA的高通量选择(美国公开的专利申请No.2005/0042641A1)。也可以通过二级结构预测来分析潜在靶位点(Heale等,2005,Nucleic Acid Res33(3):e30)。随后使用这一21mer来设计右侧偏移以在21mer5'端上包括3-9个其它核苷酸。这些其它核苷酸的序列不受限制。在一个实施方案中,加入的核糖核苷酸基于靶基因的序列。甚至在此实施方案中,不需要靶序列与反义siRNA之间完全互补。
本发明DsiRNA试剂的第一和第二寡核苷酸无需完全互补。其只需充分互补以在生物条件下退火,并且为Dicer提供底物以产生与靶序列充分互补的siRNA。锁核酸或LNA是本领域技术人员熟知的(Elmen等,2005,Nucleic Acid Res33:439-447;Kurreck等,2002,Nucleic Acid Res30:1911-1918;Crinelli等,2002,Nucleic Acid Res30:2435-2443;Braasch and Corey,2001,Chem Biol8:1-7;Bondensgaard等,2000,Chemistry6:2687-2695;Wahlestedt等,2000,Proc Natl Acad Sci USA97:5633-5638)。在一个实施方案中,LNA在有义链5'末端被并入。在另一实施方案中,LNA在双链体中的有义链的5'末端被并入,该双链体被设计成在反义链上包括3'突出。
在某些实施方案中,本发明的DsiRNA试剂具有不对称结构,其中有义链的长度为25个碱基对,且反义链的长度是27个碱基对并具有2个碱基的3'突出。在其它实施方案中,这一具有不对称结构的DsiRNA试剂在有义链的3'端还含有2个脱氧核苷酸代替两个核糖核苷酸。
含有两个单独寡核苷酸的某些DsiRNA试剂组合物可通过第三结构连接。该第三结构不会阻断Dicer对DsiRNA试剂的活性,而且不会干扰由靶基因转录的RNA的定向破坏。在一个实施方案中,第三结构可以是化学连接基团。本领域中已知许多适合的化学连接基团,并且都可以使用。或者,第三结构可以是一种寡核苷酸,其以一定方式连接DsiRNA试剂的两个寡核苷酸,以致在构成dsRNA组合物的两个寡核苷酸退火后产生发夹结构。这一发夹结构将不会阻断Dicer对DsiRNA试剂的活性,而且不会干扰KRAS RNA的定向破坏。
在某些实施方案中,本发明的抗KRAS DsiRNA试剂具有几个增进Dicer对其的加工的性质。根据这些实施方案,DsiRNA试剂具有足够长度,以致其经过Dicer加工以产生siRNA和以下至少一种性质:(i)DsiRNA试剂是不对称的,例如在有义链上具有3'突出,以及(ii)DsiRNA试剂在反义链上具有经过修饰的3'端,以引导siRNA的Dicer结合和加工而成为活性siRNA的定向。根据这些实施方案,DsiRNA试剂中最长的链包含25-35个核苷酸。在一个实施方案中,有义链包含25-30个核苷酸,并且反义链包含25-28个核苷酸。因此,得到的dsRNA在有义链的3'端上具有突出。该突出为1-4个核苷酸,例如2个核苷酸。反义链还可以具有5'磷酸。
在某些实施方案中,DsiRNA试剂的有义链被位于有义链3'端的适当修饰剂修饰,以便于Dicer加工,即,DsiRNA试剂被设计成引导Dicer结合和加工的定向。适合的修饰剂包括核苷酸,例如脱氧核糖核苷酸、双脱氧核糖核苷酸、无环核苷酸等,以及空间位阻分子,例如荧光分子等。无环核苷酸利用2-羟基乙氧基甲基取代dNMP中通常存在的2'-脱氧呋喃核糖基糖。其它核苷酸修饰剂可包括3'-脱氧腺苷(虫草素)、3'-叠氮基-3'-脱氧胸苷(AZT)、2',3'-双脱氧肌苷(ddI)、2',3'-双脱氧-3'-硫代胞苷(3TC)、2',3'-双脱氢-2',3'-双脱氧胸苷(d4T),以及3'-叠氮基-3'-脱氧胸苷(AZT)、2',3'-双脱氧-3'-硫代胞苷(3TC)和2',3'-双脱氢-2',3'-双脱氧胸苷(d4T)的单磷酸核苷酸。在一个实施方案中,使用脱氧核苷酸作为修饰剂。当利用核苷酸修饰剂时,用1-3个核苷酸修饰剂或2个核苷酸修饰剂取代有义链3'端上的核糖核苷酸。当利用空间位阻分子时,这些分子附接到反义链3'端的核糖核苷酸。因此,该链的长度不会随修饰剂的并入而改变。在另一实施方案中,本发明预期取代dsRNA中的两个DNA碱基,以引导Dicer加工的定向。在另一发明中,两个末端DNA碱基代替两个核糖核苷酸位于有义链3'端上,从而在反义链5'端和有义链3'端上形成双链体的平端,并且两个核苷酸的RNA突出位于反义链3'端上。这是一种在平端上具有DNA且在突出端上具有RNA碱基的不对称组合物。
在某些其它实施方案中,DsiRNA试剂的反义链被位于反义链3'端的适当修饰剂修饰,以便于Dicer加工,即,DsiRNA试剂被设计成引导Dicer结合和加工的定向。适合的修饰剂包括核苷酸,例如脱氧核糖核苷酸、双脱氧核糖核苷酸、无环核苷酸等,以及空间位阻分子,例如荧光分子等。无环核苷酸利用2-羟基乙氧基甲基取代dNMP中通常存在的2'-脱氧呋喃核糖基糖。其它核苷酸修饰剂可包括3'-脱氧腺苷(虫草素)、3'-叠氮基-3'-脱氧胸苷(AZT)、2',3'-双脱氧肌苷(ddI)、2',3'-双脱氧-3'-硫代胞苷(3TC)、2',3'-双脱氢-2',3'-双脱氧胸苷(d4T),以及3'-叠氮基-3'-脱氧胸苷(AZT)、2',3'-双脱氧-3'-硫代胞苷(3TC)和2',3'-双脱氢-2',3'-双脱氧胸苷(d4T)的单磷酸核苷酸。在一个实施方案中,使用脱氧核苷酸作为修饰剂。当利用核苷酸修饰剂时,用1-3个核苷酸修饰剂或2个核苷酸修饰剂取代反义链3'端上的核糖核苷酸。当利用空间位阻分子时,这些分子附接到反义链3'端的核糖核苷酸。因此,该链的长度不会随修饰剂的并入而改变。在另一实施方案中,本发明预期取代dsRNA中的两个DNA碱基,以引导Dicer加工的定向。在另一发明中,两个末端DNA碱基代替两个核糖核苷酸位于反义链3'端上,从而在有义链5'端与反义链3'端上形成双链体的平端,并且两个核苷酸的RNA突出位于有义链3'端上。这也是一种在平端上具有DNA且在突出端上具有RNA碱基的不对称组合物。
有义链与反义链在生物条件(例如,细胞的细胞质中所见的条件)下退火。此外,dsRNA的一个序列区,尤其是反义链序列区的序列长度为至少19个核苷酸,其中这些核苷酸邻近反义链3'端,并与靶KRAS RNA的核苷酸序列充分互补。
另外,DsiRNA试剂结构可经过优化以确保由Dicer裂解产生的寡核苷酸片段将成为最有效抑制基因表达的寡核苷酸部分。例如,在本发明一个实施方案中,合成DsiRNA试剂结构的27个碱基对的寡核苷酸,其中预期将抑制基因表达的21至22个碱基对的片段位于反义链3'端上。位于反义链5'端上的其余碱基将被Dicer裂解并丢弃。这一被裂解的部分可以是同源(即,基于靶序列的序列)或非同源的,并且被加入用以延伸核酸链。
US2007/0265220公开,27mer DsiRNA在血清中显示出比相当的21mer siRNA组合物提高的稳定性,即使不存在化学修饰。DsiRNA试剂的修饰(例如在反义链中包括2'-O-甲基RNA;模式如上文详述)当与加入5’磷酸结合时,可提高DsiRNA试剂的稳定性。对合成RNA双链体中的所有链加入5'-磷酸是一种价格便宜的生理学方法以赋予某种有限程度的核酸酶稳定性。
本发明DsiRNA试剂的化学修饰模式被设计成增强这些试剂的功效。因此,这些修饰被设计成避免降低DsiRNA试剂的效力;避免干扰DsiRNA试剂的Dicer加工;提高DsiRNA试剂在生物流体中的稳定性(降低核酸酶敏感性);或者阻断或避开固有免疫系统的检测。这些修饰还被设计成避免具有毒性以及避免增加成本或影响制造本发明DsiRNA试剂的便利性。
KRAS生物学和生物化学
转化是通常通过积累影响调控细胞生长和分化的基因的表达的突变来中断对细胞生长和分化的正常控制的累积方法。
血小板源性生长因子(PDGF)系统可用作供鉴别受体酪氨酸激酶底物的原型。某些酶由PDGF受体激酶激活,包括磷脂酶C和磷脂酰肌醇3'激酶、Ras鸟苷三磷酸(GTPase)激活蛋白(GAP)和类src酪氨酸激酶。GAP通过刺激21kD Ras蛋白质的GTPase活性来调控Ras蛋白质的功能。Barbacid,56Ann.Rev.Biochem.779,1987。已显示,将致癌激活的Ras显微注射到NIH3T3细胞中以诱导DNA的合成。引起Ras的致癌激活的突变会导致结合于GTP的Ras(该分子的活性形式)的结合。这些突变阻断GAP将Ras转变成无活性形式的能力。损害Ras与GAP的相互作用的突变也阻断Ras的生物功能。
尽管存在许多涉及癌发生的Ras等位基因(N-Ras、KRAS、H-Ras),但最常与结肠和胰腺癌有关的类型是KRAS。靶向KRAS等位基因mRNA某些区域的核酸分子也证明对于N-Ras和H-Ras基因的其它等位基因mRNA的功能是抑制的。
因此,使用靶向KRAS的DsiRNA试剂将提供一类新型的治疗剂,其可单独或结合其它疗法来治疗、缓解或预防癌症和/或增生性疾病、病况或病症。
已知的KRAS基因和多肽序列包括下述:
野生型KRAS序列(SEQ ID NO:1;K-Ras4A–转录变体a;GenBank登录号NM_033360.2):
GGCCGCGGCGGCGGAGGCAGCAGCGGCGGCGGCAGTGGCGGCGGCGAAGGTGGCGGCGGCTCGGCCAGTACTCCCGGCCCCCGCCATTTCGGACTGGGAGCGAGCGCGGCGCAGGCACTGAAGGCGGCGGCGGGGCCAGAGGCTCAGCGGCTCCCAGGTGCGGGAGAGAGGCCTGCTGAAAATGACTGAATATAAACTTGTGGTAGTTGGAGCTGGTGGCGTAGGCAAGAGTGCCTTGACGATACAGCTAATTCAGAATCATTTTGTGGACGAATATGATCCAACAATAGAGGATTCCTACAGGAAGCAAGTAGTAATTGATGGAGAAACCTGTCTCTTGGATATTCTCGACACAGCAGGTCAAGAGGAGTACAGTGCAATGAGGGACCAGTACATGAGGACTGGGGAGGGCTTTCTTTGTGTATTTGCCATAAATAATACTAAATCATTTGAAGATATTCACCATTATAGAGAACAAATTAAAAGAGTTAAGGACTCTGAAGATGTACCTATGGTCCTAGTAGGAAATAAATGTGATTTGCCTTCTAGAACAGTAGACACAAAACAGGCTCAGGACTTAGCAAGAAGTTATGGAATTCCTTTTATTGAAACATCAGCAAAGACAAGACAGAGAGTGGAGGATGCTTTTTATACATTGGTGAGGGAGATCCGACAATACAGATTGAAAAAAATCAGCAAAGAAGAAAAGACTCCTGGCTGTGTGAAAATTAAAAAATGCATTATAATGTAATCTGGGTGTTGATGATGCCTTCTATACATTAGTTCGAGAAATTCGAAAACATAAAGAAAAGATGAGCAAAGATGGTAAAAAGAAGAAAAAGAAGTCAAAGACAAAGTGTGTAATTATGTAAATACAATTTGTACTTTTTTCTTAAGGCATACTAGTACAAGTGGTAATTTTTGTACATTACACTAAATTATTAGCATTTGTTTTAGCATTACCTAATTTTTTTCCTGCTCCATGCAGACTGTTAGCTTTTACCTTAAATGCTTATTTTAAAATGACAGTGGAAGTTTTTTTTTCCTCTAAGTGCCAGTATTCCCAGAGTTTTGGTTTTTGAACTAGCAATGCCTGTGAAAAAGAAACTGAATACCTAAGATTTCTGTCTTGGGGTTTTTGGTGCATGCAGTTGATTACTTCTTATTTTTCTTACCAATTGTGAATGTTGGTGTGAAACAAATTAATGAAGCTTTTGAATCATCCCTATTCTGTGTTTTATCTAGTCACATAAATGGATTAATTACTAATTTCAGTTGAGACCTTCTAATTGGTTTTTACTGAAACATTGAGGGAACACAAATTTATGGGCTTCCTGATGATGATTCTTCTAGGCATCATGTCCTATAGTTTGTCATCCCTGATGAATGTAAAGTTACACTGTTCACAAAGGTTTTGTCTCCTTTCCACTGCTATTAGTCATGGTCACTCTCCCCAAAATATTATATTTTTTCTATAAAAAGAAAAAAATGGAAAAAAATTACAAGGCAATGGAAACTATTATAAGGCCATTTCCTTTTCACATTAGATAAATTACTATAAAGACTCCTAATAGCTTTTCCTGTTAAGGCAGACCCAGTATGAAATGGGGATTATTATAGCAACCATTTTGGGGCTATATTTACATGCTACTAAATTTTTATAATAATTGAAAAGATTTTAACAAGTATAAAAAATTCTCATAGGAATTAAATGTAGTCTCCCTGTGTCAGACTGCTCTTTCATAGTATAACTTTAAATCTTTTCTTCAACTTGAGTCTTTGAAGATAGTTTTAATTCTGCTTGTGACATTAAAAGATTATTTGGGCCAGTTATAGCTTATTAGGTGTTGAAGAGACCAAGGTTGCAAGGCCAGGCCCTGTGTGAACCTTTGAGCTTTCATAGAGAGTTTCACAGCATGGACTGTGTCCCCACGGTCATCCAGTGTTGTCATGCATTGGTTAGTCAAAATGGGGAGGGACTAGGGCAGTTTGGATAGCTCAACAAGATACAATCTCACTCTGTGGTGGTCCTGCTGACAAATCAAGAGCATTGCTTTTGTTTCTTAAGAAAACAAACTCTTTTTTAAAAATTACTTTTAAATATTAACTCAAAAGTTGAGATTTTGGGGTGGTGGTGTGCCAAGACATTAATTTTTTTTTTAAACAATGAAGTGAAAAAGTTTTACAATCTCTAGGTTTGGCTAGTTCTCTTAACACTGGTTAAATTAACATTGCATAAACACTTTTCAAGTCTGATCCATATTTAATAATGCTTTAAAATAAAAATAAAAACAATCCTTTTGATAAATTTAAAATGTTACTTATTTTAAAATAAATGAAGTGAGATGGCATGGTGAGGTGAAAGTATCACTGGACTAGGAAGAAGGTGACTTAGGTTCTAGATAGGTGTCTTTTAGGACTCTGATTTTGAGGACATCACTTACTATCCATTTCTTCATGTTAAAAGAAGTCATCTCAAACTCTTAGTTTTTTTTTTTTACAACTATGTAATTTATATTCCATTTACATAAGGATACACTTATTTGTCAAGCTCAGCACAATCTGTAAATTTTTAACCTATGTTACACCATCTTCAGTGCCAGTCTTGGGCAAAATTGTGCAAGAGGTGAAGTTTATATTTGAATATCCATTCTCGTTTTAGGACTCTTCTTCCATATTAGTGTCATCTTGCCTCCCTACCTTCCACATGCCCCATGACTTGATGCAGTTTTAATACTTGTAATTCCCCTAACCATAAGATTTACTGCTGCTGTGGATATCTCCATGAAGTTTTCCCACTGAGTCACATCAGAAATGCCCTACATCTTATTTCCTCAGGGCTCAAGAGAATCTGACAGATACCATAAAGGGATTTGACCTAATCACTAATTTTCAGGTGGTGGCTGATGCTTTGAACATCTCTTTGCTGCCCAATCCATTAGCGACAGTAGGATTTTTCAAACCTGGTATGAATAGACAGAACCCTATCCAGTGGAAGGAGAATTTAATAAAGATAGTGCTGAAAGAATTCCTTAGGTAATCTATAACTAGGACTACTCCTGGTAACAGTAATACATTCCATTGTTTTAGTAACCAGAAATCTTCATGCAATGAAAAATACTTTAATTCATGAAGCTTACTTTTTTTTTTTGGTGTCAGAGTCTCGCTCTTGTCACCCAGGCTGGAATGCAGTGGCGCCATCTCAGCTCACTGCAACCTCCATCTCCCAGGTTCAAGCGATTCTCGTGCCTCGGCCTCCTGAGTAGCTGGGATTACAGGCGTGTGCCACTACACTCAACTAATTTTTGTATTTTTAGGAGAGACGGGGTTTCACCCTGTTGGCCAGGCTGGTCTCGAACTCCTGACCTCAAGTGATTCACCCACCTTGGCCTCATAAACCTGTTTTGCAGAACTCATTTATTCAGCAAATATTTATTGAGTGCCTACCAGATGCCAGTCACCGCACAAGGCACTGGGTATATGGTATCCCCAAACAAGAGACATAATCCCGGTCCTTAGGTAGTGCTAGTGTGGTCTGTAATATCTTACTAAGGCCTTTGGTATACGACCCAGAGATAACACGATGCGTATTTTAGTTTTGCAAAGAAGGGGTTTGGTCTCTGTGCCAGCTCTATAATTGTTTTGCTACGATTCCACTGAAACTCTTCGATCAAGCTACTTTATGTAAATCACTTCATTGTTTTAAAGGAATAAACTTGATTATATTGTTTTTTTATTTGGCATAACTGTGATTCTTTTAGGACAATTACTGTACACATTAAGGTGTATGTCAGATATTCATATTGACCCAAATGTGTAATATTCCAGTTTTCTCTGCATAAGTAATTAAAATATACTTAAAAATTAATAGTTTTATCTGGGTACAAATAAACAGGTGCCTGAACTAGTTCACAGACAAGGAAACTTCTATGTAAAAATCACTATGATTTCTGAATTGCTATGTGAAACTACAGATCTTTGGAACACTGTTTAGGTAGGGTGTTAAGACTTACACAGTACCTCGTTTCTACACAGAGAAAGAAATGGCCATACTTCAGGAACTGCAGTGCTTATGAGGGGATATTTAGGCCTCTTGAATTTTTGATGTAGATGGGCATTTTTTTAAGGTAGTGGTTAATTACCTTTATGTGAACTTTGAATGGTTTAACAAAAGATTTGTTTTTGTAGAGATTTTAAAGGGGGAGAATTCTAGAAATAAATGTTACCTAATTATTACAGCCTTAAAGACAAAAATCCTTGTTGAAGTTTTTTTAAAAAAAGCTAAATTACATAGACTTAGGCATTAACATGTTTGTGGAAGAATATAGCAGACGTATATTGTATCATTTGAGTGAATGTTCCCAAGTAGGCATTCTAGGCTCTATTTAACTGAGTCACACTGCATAGGAATTTAGAACCTAACTTTTATAGGTTATCAAAACTGTTGTCACCATTGCACAATTTTGTCCTAATATATACATAGAAACTTTGTGGGGCATGTTAAGTTACAGTTTGCACAAGTTCATCTCATTTGTATTCCATTGATTTTTTTTTTCTTCTAAACATTTTTTCTTCAAACAGTATATAACTTTTTTTAGGGGATTTTTTTTTAGACAGCAAAAACTATCTGAAGATTTCCATTTGTCAAAAAGTAATGATTTCTTGATAATTGTGTAGTAATGTTTTTTAGAACCCAGCAGTTACCTTAAAGCTGAATTTATATTTAGTAACTTCTGTGTTAATACTGGATAGCATGAATTCTGCATTGAGAAACTGAATAGCTGTCATAAAATGAAACTTTCTTTCTAAAGAAAGATACTCACATGAGTTCTTGAAGAATAGTCATAACTAGATTAAGATCTGTGTTTTAGTTTAATAGTTTGAAGTGCCTGTTTGGGATAATGATAGGTAATTTAGATGAATTTAGGGGAAAAAAAAGTTATCTGCAGATATGTTGAGGGCCCATCTCTCCCCCCACACCCCCACAGAGCTAACTGGGTTACAGTGTTTTATCCGAAAGTTTCCAATTCCACTGTCTTGTGTTTTCATGTTGAAAATACTTTTGCATTTTTCCTTTGAGTGCCAATTTCTTACTAGTACTATTTCTTAATGTAACATGTTTACCTGGAATGTATTTTAACTATTTTTGTATAGTGTAAACTGAAACATGCACATTTTGTACATTGTGCTTTCTTTTGTGGGACATATGCAGTGTGATCCAGTTGTTTTCCATCATTTGGTTGCGCTGACCTAGGAATGTTGGTCATATCAAACATTAAAAATGACCACTCTTTTAATTGAAATTAACTTTTAAATGTTTATAGGAGTATGTGCTGTGAAGTGATCTAAAATTTGTAATATTTTTGTCATGAACTGTACTACTCCTAATTATTGTAATGTAATAAAAATAGTTACAGTGACAAAAAAAAAAAAAAA
以上带下划线的序列对应于由本发明示例性的KRAS-355和KRAS-940DsiRNA试剂所靶向的KRAS RNA序列。上述cDNA序列内的已知SNP在364位包括A/T多态性(dbSNP登录号rs17851045);在824位包括T/C多态性(dbSNP登录号rs1137282);并且在216位包括KRASG12V突变G/T多态性,如US2005/0176045中先前所述。这三个多态性位点以粗斜体显示。
野生型KRAS氨基酸序列NP_203524.1(SEQ ID NO:2;NM_033360的翻译):
MTEYKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKCDLPSRTVDTKQAQDLARSYGIPFIETSAKTRQRVEDAFYTLVREIRQYRLKKISKEEKTPGCVKIKKCIIM
野生型KRAS序列(SEQ ID NO:3;K-Ras4b–转录变体b;GenBank登录号NM_004985.3):
GGCCGCGGCGGCGGAGGCAGCAGCGGCGGCGGCAGTGGCGGCGGCGAAGGTGGCGGCGGCTCGGCCAGTACTCCCGGCCCCCGCCATTTCGGACTGGGAGCGAGCGCGGCGCAGGCACTGAAGGCGGCGGCGGGGCCAGAGGCTCAGCGGCTCCCAGGTGCGGGAGAGAGGCCTGCTGAAAATGACTGAATATAAACTTGTGGTAGTTGGAGCTGGTGGCGTAGGCAAGAGTGCCTTGACGATACAGCTAATTCAGAATCATTTTGTGGACGAATATGATCCAACAATAGAGGATTCCTACAGGAAGCAAGTAGTAATTGATGGAGAAACCTGTCTCTTGGATATTCTCGACACAGCAGGTCAAGAGGAGTACAGTGCAATGAGGGACCAGTACATGAGGACTGGGGAGGGCTTTCTTTGTGTATTTGCCATAAATAATACTAAATCATTTGAAGATATTCACCATTATAGAGAACAAATTAAAAGAGTTAAGGACTCTGAAGATGTACCTATGGTCCTAGTAGGAAATAAATGTGATTTGCCTTCTAGAACAGTAGACACAAAACAGGCTCAGGACTTAGCAAGAAGTTATGGAATTCCTTTTATTGAAACATCAGCAAAGACAAGACAGGGTGTTGATGATGCCTTCTATACATTAGTTCGAGAAATTCGAAAACATAAAGAAAAGATGAGCAAAGATGGTAAAAAGAAGAAAAAGAAGTCAAAGACAAAGTGTGTAATTATGTAAATACAATTTGTACTTTTTTCTTAAGGCATACTAGTACAAGTGGTAATTTTTGTACATTACACTAAATTATTAGCATTTGTTTTAGCATTACCTAATTTTTTTCCTGCTCCATGCAGACTGTTAGCTTTTACCTTAAATGCTTATTTTAAAATGACAGTGGAAGTTTTTTTTTCCTCTAAGTGCCAGTATTCCCAGAGTTTTGGTTTTTGAACTAGCAATGCCTGTGAAAAAGAAACTGAATACCTAAGATTTCTGTCTTGGGGTTTTTGGTGCATGCAGTTGATTACTTCTTATTTTTCTTACCAATTGTGAATGTTGGTGTGAAACAAATTAATGAAGCTTTTGAATCATCCCTATTCTGTGTTTTATCTAGTCACATAAATGGATTAATTACTAATTTCAGTTGAGACCTTCTAATTGGTTTTTACTGAAACATTGAGGGAACACAAATTTATGGGCTTCCTGATGATGATTCTTCTAGGCATCATGTCCTATAGTTTGTCATCCCTGATGAATGTAAAGTTACACTGTTCACAAAGGTTTTGTCTCCTTTCCACTGCTATTAGTCATGGTCACTCTCCCCAAAATATTATATTTTTTCTATAAAAAGAAAAAAATGGAAAAAAATTACAAGGCAATGGAAACTATTATAAGGCCATTTCCTTTTCACATTAGATAAATTACTATAAAGACTCCTAATAGCTTTTCCTGTTAAGGCAGACCCAGTATGAAATGGGGATTATTATAGCAACCATTTTGGGGCTATATTTACATGCTACTAAATTTTTATAATAATTGAAAAGATTTTAACAAGTATAAAAAATTCTCATAGGAATTAAATGTAGTCTCCCTGTGTCAGACTGCTCTTTCATAGTATAACTTTAAATCTTTTCTTCAACTTGAGTCTTTGAAGATAGTTTTAATTCTGCTTGTGACATTAAAAGATTATTTGGGCCAGTTATAGCTTATTAGGTGTTGAAGAGACCAAGGTTGCAAGGCCAGGCCCTGTGTGAACCTTTGAGCTTTCATAGAGAGTTTCACAGCATGGACTGTGTCCCCACGGTCATCCAGTGTTGTCATGCATTGGTTAGTCAAAATGGGGAGGGACTAGGGCAGTTTGGATAGCTCAACAAGATACAATCTCACTCTGTGGTGGTCCTGCTGACAAATCAAGAGCATTGCTTTTGTTTCTTAAGAAAACAAACTCTTTTTTAAAAATTACTTTTAAATATTAACTCAAAAGTTGAGATTTTGGGGTGGTGGTGTGCCAAGACATTAATTTTTTTTTTAAACAATGAAGTGAAAAAGTTTTACAATCTCTAGGTTTGGCTAGTTCTCTTAACACTGGTTAAATTAACATTGCATAAACACTTTTCAAGTCTGATCCATATTTAATAATGCTTTAAAATAAAAATAAAAACAATCCTTTTGATAAATTTAAAATGTTACTTATTTTAAAATAAATGAAGTGAGATGGCATGGTGAGGTGAAAGTATCACTGGACTAGGAAGAAGGTGACTTAGGTTCTAGATAGGTGTCTTTTAGGACTCTGATTTTGAGGACATCACTTACTATCCATTTCTTCATGTTAAAAGAAGTCATCTCAAACTCTTAGTTTTTTTTTTTTACAACTATGTAATTTATATTCCATTTACATAAGGATACACTTATTTGTCAAGCTCAGCACAATCTGTAAATTTTTAACCTATGTTACACCATCTTCAGTGCCAGTCTTGGGCAAAATTGTGCAAGAGGTGAAGTTTATATTTGAATATCCATTCTCGTTTTAGGACTCTTCTTCCATATTAGTGTCATCTTGCCTCCCTACCTTCCACATGCCCCATGACTTGATGCAGTTTTAATACTTGTAATTCCCCTAACCATAAGATTTACTGCTGCTGTGGATATCTCCATGAAGTTTTCCCACTGAGTCACATCAGAAATGCCCTACATCTTATTTCCTCAGGGCTCAAGAGAATCTGACAGATACCATAAAGGGATTTGACCTAATCACTAATTTTCAGGTGGTGGCTGATGCTTTGAACATCTCTTTGCTGCCCAATCCATTAGCGACAGTAGGATTTTTCAAACCTGGTATGAATAGACAGAACCCTATCCAGTGGAAGGAGAATTTAATAAAGATAGTGCTGAAAGAATTCCTTAGGTAATCTATAACTAGGACTACTCCTGGTAACAGTAATACATTCCATTGTTTTAGTAACCAGAAATCTTCATGCAATGAAAAATACTTTAATTCATGAAGCTTACTTTTTTTTTTTGGTGTCAGAGTCTCGCTCTTGTCACCCAGGCTGGAATGCAGTGGCGCCATCTCAGCTCACTGCAACCTCCATCTCCCAGGTTCAAGCGATTCTCGTGCCTCGGCCTCCTGAGTAGCTGGGATTACAGGCGTGTGCCACTACACTCAACTAATTTTTGTATTTTTAGGAGAGACGGGGTTTCACCCTGTTGGCCAGGCTGGTCTCGAACTCCTGACCTCAAGTGATTCACCCACCTTGGCCTCATAAACCTGTTTTGCAGAACTCATTTATTCAGCAAATATTTATTGAGTGCCTACCAGATGCCAGTCACCGCACAAGGCACTGGGTATATGGTATCCCCAAACAAGAGACATAATCCCGGTCCTTAGGTAGTGCTAGTGTGGTCTGTAATATCTTACTAAGGCCTTTGGTATACGACCCAGAGATAACACGATGCGTATTTTAGTTTTGCAAAGAAGGGGTTTGGTCTCTGTGCCAGCTCTATAATTGTTTTGCTACGATTCCACTGAAACTCTTCGATCAAGCTACTTTATGTAAATCACTTCATTGTTTTAAAGGAATAAACTTGATTATATTGTTTTTTTATTTGGCATAACTGTGATTCTTTTAGGACAATTACTGTACACATTAAGGTGTATGTCAGATATTCATATTGACCCAAATGTGTAATATTCCAGTTTTCTCTGCATAAGTAATTAAAATATACTTAAAAATTAATAGTTTTATCTGGGTACAAATAAACAGGTGCCTGAACTAGTTCACAGACAAGGAAACTTCTATGTAAAAATCACTATGATTTCTGAATTGCTATGTGAAACTACAGATCTTTGGAACACTGTTTAGGTAGGGTGTTAAGACTTACACAGTACCTCGTTTCTACACAGAGAAAGAAATGGCCATACTTCAGGAACTGCAGTGCTTATGAGGGGATATTTAGGCCTCTTGAATTTTTGATGTAGATGGGCATTTTTTTAAGGTAGTGGTTAATTACCTTTATGTGAACTTTGAATGGTTTAACAAAAGATTTGTTTTTGTAGAGATTTTAAAGGGGGAGAATTCTAGAAATAAATGTTACCTAATTATTACAGCCTTAAAGACAAAAATCCTTGTTGAAGTTTTTTTAAAAAAAGCTAAATTACATAGACTTAGGCATTAACATGTTTGTGGAAGAATATAGCAGACGTATATTGTATCATTTGAGTGAATGTTCCCAAGTAGGCATTCTAGGCTCTATTTAACTGAGTCACACTGCATAGGAATTTAGAACCTAACTTTTATAGGTTATCAAAACTGTTGTCACCATTGCACAATTTTGTCCTAATATATACATAGAAACTTTGTGGGGCATGTTAAGTTACAGTTTGCACAAGTTCATCTCATTTGTATTCCATTGATTTTTTTTTTCTTCTAAACATTTTTTCTTCAAACAGTATATAACTTTTTTTAGGGGATTTTTTTTTAGACAGCAAAAACTATCTGAAGATTTCCATTTGTCAAAAAGTAATGATTTCTTGATAATTGTGTAGTAATGTTTTTTAGAACCCAGCAGTTACCTTAAAGCTGAATTTATATTTAGTAACTTCTGTGTTAATACTGGATAGCATGAATTCTGCATTGAGAAACTGAATAGCTGTCATAAAATGAAACTTTCTTTCTAAAGAAAGATACTCACATGAGTTCTTGAAGAATAGTCATAACTAGATTAAGATCTGTGTTTTAGTTTAATAGTTTGAAGTGCCTGTTTGGGATAATGATAGGTAATTTAGATGAATTTAGGGGAAAAAAAAGTTATCTGCAGATATGTTGAGGGCCCATCTCTCCCCCCACACCCCCACAGAGCTAACTGGGTTACAGTGTTTTATCCGAAAGTTTCCAATTCCACTGTCTTGTGTTTTCATGTTGAAAATACTTTTGCATTTTTCCTTTGAGTGCCAATTTCTTACTAGTACTATTTCTTAATGTAACATGTTTACCTGGAATGTATTTTAACTATTTTTGTATAGTGTAAACTGAAACATGCACATTTTGTACATTGTGCTTTCTTTTGTGGGACATATGCAGTGTGATCCAGTTGTTTTCCATCATTTGGTTGCGCTGACCTAGGAATGTTGGTCATATCAAACATTAAAAATGACCACTCTTTTAATTGAAATTAACTTTTAAATGTTTATAGGAGTATGTGCTGTGAAGTGATCTAAAATTTGTAATATTTTTGTCATGAACTGTACTACTCCTAATTATTGTAATGTAATAAAAATAGTTACAGTGACAAAAAAAAAAAAAAA
以上带下划线的序列对应于由本发明示例性KRAS-355和KRAS-940DsiRNA试剂所靶向的KRAS RNA序列。上述cDNA序列内的已知SNP在364位包括A/T多态性(dbSNP登录号rs17851045);在700位包括T/C多态性(dbSNP登录号rs1137282);且在216位包括KRAS G12V突变G/T多态性,如US2005/0176045中先前所述。这三个多态性位点以粗斜体显示。
野生型KRAS氨基酸序列NP_004976.2(SEQ ID NO:4;NM_004985的翻译):
MTEYKLVVVGAGGVGKSALTIQLIQNHFVDEYDPTIEDSYRKQVVIDGETCLLDILDTAGQEEYSAMRDQYMRTGEGFLCVFAINNTKSFEDIHHYREQIKRVKDSEDVPMVLVGNKCDLPSRTVDTKQAQDLARSYGIPFIETSAKTRQGVDDAFYTLVREIRKHKEKMSKDGKKKKKKSKTKCVIM
用以评估DsiRNA KRAS抑制活性的体外测定
可以使用在无细胞体系中重现(recapitulate)RNAi的体外测定来评估靶向KRASRNA序列的DsiRNA构建体,并由此评估DsiRNA的KRAS特异性基因抑制活性(本文中又称为KRAS抑制活性)。该测定包括Tuschl等,1999,Genes and Development,13,3191-3197以及Zamore等,2000,Cell,101,25-33中所述的系统,使该系统适合用于针对KRAS RNA的DsiRNA试剂。使用源自于合胞体胚层的果蝇(Drosophila)提取物在体外重建RNAi活性。靶RNA是使用T7RNA聚合酶由适合的KRAS表达质粒在体外转录产生或通过化学合成产生。有义和反义DsiRNA链(例如各20μM)通过以下方式退火:在缓冲液(例如100mM乙酸钾、30mM HEPES-KOH,pH7.4,2mM乙酸镁)中于90℃下孵育1分钟,随后在37℃下孵育1小时,接着在裂解缓冲液(例如100mM乙酸钾、30mM pH7.4的HEPES-KOH、2mM乙酸镁)中稀释。可通过在琼脂糖凝胶上于TBE缓冲液中进行凝胶电泳并用溴化乙锭染色来监测退火。使用去除卵膜并裂解的在酵母糖蜜琼脂上收集的Oregon R苍蝇的0至小时大的胚胎来制备果蝇裂解物。将该裂解物离心,并分离上清液。本测定包括含有50%裂解物[体积比]、RNA(10-50pM最终浓度)和含DsiRNA(10nM最终浓度)的10%[体积比]裂解缓冲液的反应混合物。该反应混合物还含有10mM磷酸肌酸、10μg/ml肌酸磷酸激酶、100μm GTP、100μM UTP、100μM CTP、500μM ATP、5mM DTT、0.1U/μL RNasin(Promega)和100μM各氨基酸。乙酸钾的最终浓度被调整到100mM。在冰上预先组合各反应物,并在25℃下预先孵育10分钟,之后加入RNA,接着在25℃下再孵育60分钟。用4体积1.25x被动裂解缓冲液(Promega)中止反应。借助RT-PCR分析或本领域中已知的其它方法测定靶RNA裂解,并与反应中不包含DsiRNA的对照反应相比较。
或者,通过在[α-32P]CTP存在下进行体外转录来制备供测定的内部标记的靶RNA,使其经过G50Sephadex柱进行自旋色谱分离,并且不经进一步纯化即用作靶RNA。任选地,使用T4聚核苷酸激酶在靶RNA5'端标记32P。如上文所述进行测定,并在凝胶的自体放射照片上可见由RNAi产生的特定RNA裂解产物。通过PHOSPHOR (放射自显影术)定量表示完整对照RNA或由不含DsiRNA的对照反应得到的RNA以及由本测定产生的裂解产物的谱带来测定裂解百分比。
在一个实施方案中,使用这一测定来确定KRAS RNA靶中DsiRNA介导的RNAi裂解的靶位点,其中例如通过经过标记的靶RNA的电泳或通过RNA印迹,以及通过本领域熟知的其它方法分析本测定反应,针对KRAS RNA靶的RNAi介导的裂解作用来筛选多种DsiRNA构建体。
在某些实施方案中,如果例如在体系、细胞、组织或生物体中观察到相对于适合对照物KRAS RNA水平的50%降低,那么就认为本发明的DsiRNA具有KRAS抑制活性。用于测定本发明DsiRNA的KRAS抑制活性的其它限度和界限如上文所述。
抗KRAS DsiRNA试剂的缀合和递送
在某些实施方案中,本发明涉及一种用于治疗患有KRAS相关性疾病或病症或有发生KRAS相关性疾病或病症的风险的受试者的方法。在这些实施方案中,DsiRNA可充当用于控制KRAS相关性疾病或病症的新型治疗剂。本方法包括对患者(例如,人)施用本发明的药物组合物,以降低KRAS RNA的表达、水平和/或活性。本发明的DsiRNA也可能降低由KRASRNA编码的多肽的表达、水平和/或活性,甚至在所述DsiRNA是针对KRAS转录物的非编码区(例如,靶向5’UTR或3’UTR序列)的情形。由于本发明的DsiRNA具有高度特异性,故其可任选以等位基因特异性方式(其中多态性等位基因存在于个体和/或群体内)特异性靶向细胞和组织的KRAS序列。
在治疗KRAS相关性疾病或病症时,可使DsiRNA与受试者的细胞或组织(例如,表现KRAS调控异常和/或以其它方式被靶向以降低KRAS水平的受试者的细胞或组织)接触。例如,可以使与全部或一部分KRAS RNA序列基本上相同的DsiRNA在体外或体内与此类细胞接触或引入此类细胞中。类似地,可以将与全部或一部分KRAS RNA序列基本上相同的DsiRNA直接施用于患有KRAS相关性疾病或病症或者有发生该疾病或病症风险的受试者。
本发明DsiRNA试剂的治疗用途可涉及使用DsiRNA试剂的制剂,其包含多种不同的DsiRNA试剂序列。例如,可将两种或更多、三种或更多、四种或更多、五种或更多等先前所述的试剂组合以产生例如靶向KRAS RNA的多个不同区域的制剂,或者不仅靶向靶KRASRNA,而且还靶向例如与KRAS相关性疾病或病症有关的细胞靶基因的制剂。本发明的DsiRNA试剂也可构造成以使DsiRNA试剂中每一条链独立地靶向KRAS RNA的两个或更多个区域,或者使DsiRNA试剂中的一条链靶向本领域中已知的KRAS的细胞靶基因。
使用靶向靶核酸分子中不止一个区域的多功能DsiRNA分子还可以提供对KRASRNA水平和表达的有效抑制。例如,本发明的单一多功能DsiRNA构建体可同时靶向KRAS-355和KRAS-940位点;另外和/或或者,本发明的单一或多功能试剂可被设计成对KRAS的某一剪接变体的靶向选择性高于另一种。
因此,本发明的DsiRNA试剂可单独或者组合或结合其它药物一起用于治疗、抑制、减轻或预防KRAS相关性疾病或病症。例如,在适于治疗的条件下,DsiRNA分子可单独或与一种或多种药物组合施用于受试者,或者可施用于本领域技术人员显而易见的其它适合的细胞。
DsiRNA分子还可以与其它已知的治疗组合用于治疗、抑制、减轻或预防受试者或生物体的KRAS相关性疾病或病症。例如,如本领域中所已知的,所述分子可与一种或多种已知化合物、治疗或程序组合用于治疗、抑制、减轻或预防受试者或生物体的KRAS相关性疾病或病症。
本发明DsiRNA试剂可以与另一部分(例如,非核酸部分,例如肽)、有机化合物(例如,染料、胆固醇等)缀合(例如,在其有义链或反义链的5’或3’末端)或未缀合。与相应未缀合的DsiRNA试剂相比较,按此方式修饰DsiRNA试剂可以提高细胞吸收或增强所得DsiRNA试剂衍生物的细胞靶向活性,可用于追踪细胞中的DsiRNA试剂衍生物,或与相应未缀合的DsiRNA试剂相比提高该DsiRNA试剂衍生物的稳定性。
引入核酸、载体和宿主细胞的方法
可以将本发明的DsiRNA试剂直接引入细胞(即,经细胞内)中;或在细胞外引入生物体内腔、胞间隙、循环中,经由口引入或者可以通过在含有核酸的溶液中浸浴细胞或生物体来引入。血管或血管外循环、血液或淋巴系统以及脑脊髓液都是可以引入核酸的位点。
本发明的DsiRNA试剂可以使用本领域中已知的核酸递送方法引入,包括注入含有核酸的溶液、用覆盖有核酸的粒子轰击、在核酸溶液中浸泡细胞或生物体,或者在核酸存在下对细胞膜进行电穿孔。也可以使用本领域中已知的用于将核酸引入细胞中的其它方法,例如脂质介导的载体转运、化学制品介导的转运,和阳离子型脂质体转染(例如磷酸钙)等。核酸可以与发挥以下一种或多种活性的其它组分一起引入:增强细胞对核酸的吸收,或以其它方式增加对靶KRAS RNA的抑制。
具有靶KRAS RNA的细胞可来自生殖系或体细胞、全能或多能、分裂或非分裂、实质或上皮、永生化或经过转化的细胞等。该细胞可以是干细胞或分化的细胞。分化的细胞类型包括脂肪细胞、成纤维细胞、肌细胞、心肌细胞、内皮细胞、神经元、神经胶质、血液细胞、巨核细胞、淋巴细胞、巨噬细胞、嗜中性粒细胞、嗜酸性粒细胞、嗜碱性粒细胞、肥大细胞、白细胞、粒细胞、角化细胞、软骨细胞、成骨细胞、破骨细胞、肝细胞和内分泌或外分泌腺的细胞。
取决于特定靶KRAS RNA序列和所递送的DsiRNA试剂的剂量,这一方法可引起KRAS RNA功能的部分或完全丧失。例如,使靶细胞中RNA的水平或表达(KRAS RNA表达或编码的多肽的表达)降低或损失至少50%、60%、70%、80%、90%、95%或者99%或更高。抑制KRASRNA水平或表达是指不存在(或明显降低)KRAS RNA或KRAS RNA编码的蛋白质的水平。特异性是指抑制KRAS RNA,同时对细胞中其它基因无明显影响的能力。抑制的结果可以通过检验细胞或生物体的外在性质或生物化学技术来确定,所述生物化学技术诸如RNA溶液杂交、核酸酶保护、Northern杂交、逆转录、用微阵列监测基因表达、抗体结合、酶联免疫吸附测定(ELISA)、蛋白质印迹法、放射免疫测定(RIA)、其它免疫测定和荧光激活的细胞分析法(FACS)等。也可以根据在体外或体内施用本发明的DsiRNA试剂对KRAS相关性疾病或病症(例如,肿瘤形成、生长、转移等)的发生/进展的影响,来测量DsiRNA试剂对靶KRAS RNA序列的抑制。肿瘤或癌症的治疗和/或肿瘤或癌症细胞水平的降低可包括停止肿瘤或癌症细胞生长或降低肿瘤或癌症细胞水平,或使肿瘤或癌症细胞水平降低例如10%、20%、30%、40%、50%、60%、70%、80%、90%、95%或99%或更多,并且也可以用指数术语度量,例如通过对细胞、组织或受试者施用本发明的DsiRNA试剂,可以使癌症细胞水平降低到例如1/10、1/100、1/1000、1/105、1/106、1/107
对于细胞系或全生物体中RNA介导的抑制,可以测量蛋白质产物易于测定的报告基因或药物抗性基因的表达。这些报告基因包括乙酰羟酸合成酶(AHAS)、碱性磷酸酶(AP)、β半乳糖苷酶(LacZ)、β葡糖苷酶(GUS)、氯霉素乙酰转移酶(CAT)、绿色荧光蛋白(GFP)、辣根过氧化物酶(HRP)、荧光素酶(Luc)、胭脂碱合成酶(NOS)、章鱼碱合成酶(OCS)和其衍生物。可以使用可赋予对氨苄青霉素、博莱霉素、氯霉素、庆大霉素、潮霉素、卡那霉素、林可霉素、甲氨蝶呤、草胺膦、嘌呤霉素和四环素的抗性的多种选择标记物。取决于测定,基因表达量的定量允许测定与根据本发明的未处理的细胞相比较超过10%、33%、50%、90%、95%或99%的抑制程度。
较低剂量的注射物质和施用RNA沉默试剂后的较长时间可使较少部分的细胞(例如,至少10%、20%、50%、75%、90%或95%的靶细胞)受到抑制。细胞中基因表达的定量可在靶KRAS RNA积累或靶蛋白质翻译水平下显示类似的抑制量。例如,可以通过评估细胞中基因产物的量来测定抑制效率;可以用具有在用于抑制性DsiRNA的区域外部的核苷酸序列的杂交探针检测RNA,或可以用针对该区域的多肽序列产生的抗体检测翻译的多肽。
引入的DsiRNA试剂的量应使每一细胞递送至少一个拷贝。较高的物质剂量(例如,每一细胞至少5、10、100、500或1000个拷贝)可产生更有效的抑制;较低剂量也可用于特定应用。
药物组合物
在某些实施方案中,本发明提供一种药物组合物,其包含本发明的DsiRNA试剂。DsiRNA试剂样品可通过使足够部分的样品进入细胞中以诱导基因沉默(如果发生的话)的任何方式来适当地配制并引入细胞环境中。本领域中已知许多dsRNA制剂,并且都可以使用,只要该dsRNA能够进入靶细胞中以便其发挥作用即可。参见例如,美国公开的专利申请No.2004/0203145A1和No.2005/0054598A1。例如,本发明的DsiRNA试剂可在缓冲溶液(例如磷酸盐缓冲的生理盐水溶液)、脂质体、微胞结构和衣壳中配制。具有阳离子脂质的DsiRNA试剂的制剂可有助于将DsiRNA试剂转染到细胞中。例如,可以使用阳离子脂质,例如lipofectin(美国专利No.5,705,188);阳离子丙三醇衍生物;和聚阳离子分子,例如聚赖氨酸(公开的PCT国际申请WO97/30731)。适合的脂质包括Oligofectamine、Lipofectamine(Life Technologies)、NC388(Ribozyme Pharmaceuticals,Inc.,Boulder,Colo.)或FuGene6(Roche),所有这些脂质都可以根据制造商的说明使用。
这类组合物通常包含核酸分子和药学上可接受的载体。本文中使用的表述“药学上可接受的载体”包括生理盐水、溶剂、分散介质、包衣、抗细菌剂和抗真菌剂、等渗剂和吸收延迟剂等,这些都与药物的施用相适应。补充的活性化合物也可以并入组合物中。
配制药物组合物应与其预定的施用途径相适应。施用途径的实例包括肠胃外(例如,静脉内)、皮内、皮下、口服(例如,吸入)、透皮(局部)、透粘膜和直肠施用。用于肠胃外、皮内或皮下应用的溶液或悬浮剂可包含以下组分:无菌稀释剂,例如注射用水、生理盐水溶液、非挥发性油、聚乙二醇、丙三醇、丙二醇或其它合成溶剂;抗细菌剂,例如苯甲醇或对羟基苯甲酸甲酯;抗氧化剂,例如抗坏血酸或亚硫酸氢钠;螯合剂,例如乙二胺四乙酸;缓冲剂,例如乙酸盐、柠檬酸盐或磷酸盐;以及用于调整紧张性的试剂,例如氯化钠或右旋糖。pH值可以用酸或碱调整,例如用盐酸或氢氧化钠调整。肠胃外制剂可封闭在玻璃或塑料制的安瓿、一次性注射器或多剂量小瓶中。
适于注射使用的药物组合物包括无菌水溶液(在水溶性情况下)或分散液,以及用于临时制备无菌可注射溶液或分散液的无菌粉末。对于静脉内施用,适合的载体包括生理盐水、抑菌水、Cremophor EL.TM.(BASF,Parsippany,N.J.)或磷酸盐缓冲的生理盐水(PBS)。在所有情况下,组合物都必须是无菌的,并且应该是液体以便于注射。其应在制造和储存条件下稳定,并且必须保藏免受微生物(例如细菌和真菌)的污染作用。载体可以是含有例如水、乙醇、多元醇(例如丙三醇、丙二醇和液体聚乙二醇等)和其适合的混合物的溶剂或分散介质。例如,通过使用包衣(如卵磷脂)、在分散液情况下通过保持所需粒径以及通过使用表面活性剂,可以保持适宜的流动性。防止微生物的作用可通过各种抗细菌剂和抗真菌剂实现,例如对羟基苯甲酸酯、氯丁醇、苯酚、抗坏血酸、硫柳汞等。在许多情况下,其优选在组合物中包含等渗剂,例如糖、多元醇(例如甘露醇、山梨醇)、氯化钠。通过在组合物中包含延迟吸收的试剂,例如单硬脂酸铝和明胶,可以延长可注射组合物的吸收。
无菌可注射溶液可以通过将所需量的活性化合物与(必要时)上文所列成分中的一种或成分的组合并入适当的溶剂中,随后进行过滤灭菌来制备。一般说来,分散液是通过将活性化合物并入无菌媒介物中来制备,该无菌媒介物含有基础分散介质和选自上文所列成分的所需其它成分。在用于制备无菌可注射溶液的无菌粉末的情况下,优选的制备方法是真空干燥法和冷冻干燥法,该方法得到含有活性成分与来自其先前无菌过滤的溶液的任何其它所需成分的粉末。
口服组合物一般包含惰性稀释剂或可食用的载体。出于口服治疗施用的目的,活性化合物可与赋形剂合并,并以片剂、锭剂或胶囊(例如,明胶胶囊)的形式使用。口服组合物也可以使用流体载体制备,以用作洗口药。可包含药学上相容的粘合剂和/或佐剂材料作为组合物的一部分。片剂、丸剂、胶囊、锭剂等可含有以下具有类似性质的成分或化合物中任一种:粘合剂,例如微晶纤维素、黄芪胶或明胶;赋形剂,例如淀粉或乳糖;崩解剂,例如海藻酸、Primogel或玉米淀粉;润滑剂,例如硬脂酸镁或Sterotes;助流剂,例如胶状二氧化硅;甜味剂,例如蔗糖或糖精;或调味剂,例如薄荷、水杨酸甲酯或橙味调味剂。
对于通过吸入施用,化合物是以气雾剂喷雾形式递送,该气雾剂来自压力容器或含有适合推进剂(例如,气体,如二氧化碳)分配器,或喷雾器。这些方法包括美国专利No.6,468,798中所述的那些。
全身性施用也可以通过透粘膜或透皮方式实现。对于透粘膜或透皮施用,在制剂中可以使用适于穿透屏障的渗透剂。这类渗透剂是本领域中一般已知的,并且包括例如适于透粘膜施用的清洁剂、胆汁盐和梭链孢酸衍生物。透粘膜施用可以通过使用鼻喷雾或栓剂实现。对于透皮施用,活性化合物被配制成本领域中一般已知的药膏、软膏、凝胶或乳膏。
化合物也可以被制备成栓剂(例如,利用常规的栓剂基质,例如可可脂和其它甘油酯)或保留灌肠剂形式供直肠递送。
化合物还可以通过使用本领域中已知的方法转染或感染施用,所述方法包括但不限于McCaffrey等(2002),Nature,418(6893),38-9(水动力学转染);Xia等(2002),Nature Biotechnol.,20(10),1006-10(病毒介导的递送);或Putnam(1996),Am.J.HealthSyst.Pharm.53(2),151-160,Am.J.Health Syst.Pharm.勘误表53(3),325(1996)中所述的方法。
化合物也可以通过适于施用核酸试剂(例如DNA疫苗)的方法施用。这些方法包括基因枪、生物注射器(bio injector)和皮肤贴片,以及无针方法,例如美国专利No.6,194,389中公开的微粒DNA疫苗技术,和美国专利No.6,168,587中公开的利用粉末形式疫苗的哺乳动物透皮无针疫苗接种技术。另外,鼻内递送也是可能的,尤其是如Hamajima等(1998),Clin.Immunol.Immunopathol.,88(2),205-10等中所述。还可以使用脂质体(例如,如美国专利No.6,472,375中所述)和微胶囊包封技术。也可以使用生物可降解的可靶向微粒递送系统(例如,如美国专利No.6,471,996中所述)。
在一个实施方案中,活性化合物是用保护化合物免于从身体迅速消除的载体制备,例如控制释放制剂,包括植入物和微胶囊包封的递送系统。可以使用生物可降解、生物相容性聚合物,例如乙烯乙酸乙烯酯、聚酸酐、聚乙醇酸、胶原蛋白、聚原酸酯和聚乳酸。这类制剂可以使用标准技术制备。这些物质也可以从Alza Corporation和NovaPharmaceuticals,Inc商购。脂质体悬浮液(包括带有针对病毒抗原的单克隆抗体的靶向受感染细胞的脂质体)也可以用作药学上可接受的载体。这些都可以根据本领域技术人员已知的方法,例如美国专利No.4,522,811中所述的方法制备。
这些化合物的毒性和治疗功效可以在细胞培养物或实验动物中借助标准医药程序测定,例如测定LD50(对50%群体致死的剂量)和ED50(对50%群体治疗有效的剂量)。毒性与治疗作用的剂量比率就是治疗指数,而且它可以表示为比率LD50/ED50。优选表现高治疗指数的化合物。虽然可以使用表现毒副作用的化合物,但应小心设计使这些化合物靶向受影响组织的部位的递送系统,以便使对未受感染的细胞的潜在损害减到最小,并由此降低副作用。
从细胞培养测定和动物研究得到的数据可用于配制用于人的剂量范围。这类化合物的剂量优选处于包括ED50同时具有极小或无毒性的循环浓度的范围内。剂量可以取决于所用剂型和所用施用途径而在此范围内变动。对于本发明方法中使用的化合物,治疗有效剂量最初可由细胞培养测定估计。可以在动物模型中配制剂量,以达到包括如在细胞培养物中所测定的IC50(即,测试化合物的浓度应达到症状的半数最大抑制)的循环血浆浓度范围。这类信息可用于更精确地确定适用于人的剂量。血浆水平可以例如通过高效液相色谱法测定。
如本文所定义,核酸分子的治疗有效量(即,有效剂量)取决于所选核酸。例如,如果选择编码DsiRNA试剂的质粒,那么可以施用范围在约1pg至1000mg的单一剂量;在一些实施方案中,可以施用10pg、30pg、100pg或1000pg,或者10ng、30ng、100ng或1000ng,或者10μg、30μg、100μg或1000μg,或者10mg、30mg、100mg或1000mg。在一些实施方案中,可施用1-5g组合物。组合物可以每天施用一次或多次到每周施用一次或多次;包括每隔一天一次。本领域技术人员应理解,某些因素会影响有效治疗受试者所需的剂量和时程,这些因素包括但不限于,疾病或病症的严重程度、先前的治疗、受试者的一般健康状况和/或年龄,以及存在的其它疾病。此外,用治疗有效量的蛋白质、多肽或抗体治疗受试者可包括单次治疗,或优选可包括一系列治疗。
本发明的核酸分子可使用本领域中已知的方法(包括Xia等,(2002),同上文中所述的那些方法)插入表达构建体中,例如病毒载体、逆转录病毒载体、表达盒或质粒病毒载体。表达构建体可通过例如吸入、口服、静脉内注射、局部施用(参见美国专利No.5,328,470)或通过定位注射(参见例如,Chen等(1994),Proc.Natl.Acad.Sci.USA,91,3054-3057)递送给受试者。递送载体的药物制剂可包括溶于可接受的稀释剂中的载体,或者可包含其中包埋有递送媒介物的缓慢释放基质。或者,在由重组细胞完整产生整个递送载体(例如,逆转录病毒载体)的情况下,药物制剂可包含一个或多个产生基因递送系统的细胞。
表达构建体可以是用于适当表达系统的构建体,并且包括但不限于,逆转录病毒载体、线性表达盒、质粒和病毒或病毒源性载体,如本领域中所已知。这类表达构建体可包含一个或多个诱导性启动子、RNA Pol III启动子系统(例如U6snRNA启动子或H1RNA聚合酶III启动子)或本领域中已知的其它启动子。构建体可包括siRNA的一条或两条链。表达两条链的表达构建体也可以包括连接两条链的环结构,或者每一条链可在相同构建体内由单独启动子单独转录。每一条链还可以由单独表达构建体转录,例如Tuschl(2002,NatureBiotechnol20:500-505)。
应理解,将DsiRNA试剂引入细胞环境中的方法将取决于细胞类型和其环境组成。例如,当在液体内发现细胞时,一种优选的制剂是例如在lipofectamine中与脂质制剂一起的制剂,并且可以将DsiRNA试剂直接加入细胞的液体环境中。脂质制剂也可以例如通过静脉内、肌肉内或腹腔内注射,或口服,或者通过吸入或本领域中已知的其它方法施用于动物。当制剂适于施用于动物,例如哺乳动物且更具体为人时,制剂也是药学上可接受的。用于施用寡核苷酸的药学上可接受的制剂是已知的并且可以使用。在一些情况下,优选在缓冲液或生理盐水溶液中配制DsiRNA试剂,并将配制好的DsiRNA试剂直接注射到细胞中,如利用卵母细胞进行的研究中的那样。也可以直接注射DsiRNA试剂双链体。有关引入dsRNA(例如,DsiRNA试剂)的适当方法,参见美国公开的专利申请No.2004/0203145A1。
须引入适量的DsiRNA试剂,而且这些量可以使用标准方法凭经验确定。通常,在细胞环境中,个别DsiRNA试剂种类的有效浓度将为50纳摩尔或更低、10纳摩尔或更低,或者可以使用1纳摩尔或更低浓度的组合物。在另一实施方案中,可以在许多情况下使用利用200皮摩尔或更低、100皮摩尔浓或更低、50皮摩尔或更低、20皮摩尔或更低浓度且甚至10皮摩尔或更低、5皮摩尔或更低、2皮摩尔或更低或1皮摩尔或更低浓度的方法。
所述方法可以通过将DsiRNA试剂组合物加到可使细胞存活的细胞外基质中来进行,条件是配制DsiRNA试剂组合物以使足量的DsiRNA试剂可进入细胞以发挥其作用。例如,所述方法适用于液体(例如液体培养物或细胞生长培养基)中、组织外植体中或全生物体(包括动物,例如哺乳动物,尤其是人)中存在的细胞。
KRAS RNA的水平或活性可通过本领域中现已知的或将来将开发的适合方法测定。应了解,用于测量靶RNA和/或靶RNA表达的方法可以取决于靶RNA的性质。例如,在靶KRAS RNA序列编码蛋白质的情况下,术语“表达”可指源自于KRAS基因(基因组或外源来源)的蛋白质或KRAS RNA/转录物。在这些情况下,可以通过直接测量KRAS RNA/转录物的量或通过测量KRas蛋白质的量来测定靶KRAS RNA的表达。蛋白质可以在蛋白质测定中测量,例如通过染色或免疫印迹法测量,或者如果蛋白质催化可测量的反应,那么可以通过测量反应速率来进行测量。所有这些方法都是本领域中已知的并且都可以使用。在打算测量靶KRAS RNA水平的情况下,可以使用本领域公认的用于检测RNA水平的方法(例如,RT-PCR、RNA印迹等)。在利用本发明的DsiRNA试剂靶向KRAS RNA时,预期也可以通过在体外或体内或者细胞提取物中测量DsiRNA试剂降低受试者、组织、细胞中KRAS RNA或蛋白质水平的功效来确定KRAS相关性表型(例如,疾病或病症,例如,癌症或肿瘤形成、生长、转移、扩散)减少的程度。上述测量法可针对细胞、细胞提取物、组织、组织提取物或其它适合的源材料进行。
KRAS RNA的表达是否降低可以通过能可靠地检测RNA水平改变的适合方法来确定。通常,通过将未消化的DsiRNA引入细胞环境中,以致该DsiRNA试剂的至少一部分进入细胞质中,并随后测量靶RNA的水平来确定。对同样的未经过处理的细胞进行相同测量,并比较由各测量获得的结果。
DsiRNA试剂可以配制成药物组合物形式,该药物组合物包含药理学有效量的DsiRNA试剂和药学上可接受的载体。药理学或治疗有效量是指有效产生预期药理学、治疗或预防结果的DsiRNA试剂的量。短语“药理学有效量”或“治疗有效量”或简单地“有效量”是指有效产生预期药理学、治疗或预防结果的RNA的量。例如,如果当可测量的疾病或病症相关性参数降低至少20%时,认为给定的临床治疗是有效的,那么用于治疗该疾病或病症的药物的治疗有效量是实现该参数至少20%降低所需的量。
适当配制的本发明的药物组合物可借助本领域中已知的方式施用,例如通过肠胃外途径,包括静脉内、肌肉内、腹膜内、皮下,透皮、气道(气雾剂)、直肠、阴道和局部(包括口腔和舌下)施用。在一些实施方案中,药物组合物是通过静脉内或肠胃内(intraparenteral)输注或注射施用。
一般说来,dsRNA的适当剂量单位将在每天每公斤接受者体重0.001至0.25毫克的范围内,或在每天每公斤体重0.01至20微克的范围内,或在每天每公斤体重0.01至10微克的范围内,或在每天每公斤体重0.10至5微克的范围内,或在每天每公斤体重0.1至2.5微克的范围内。包含dsRNA的药物组合物可每天施用一次。然而,治疗剂也可以用含有2、3、4、5、6或更多亚剂量的剂量单位在一天中按适宜的时间间隔给药。在此情况下,每一亚剂量中所含的dsRNA必须相应地降低,以便达到总日剂量单位。剂量单位也可以混配用于单次剂量,经数天例如使用常规持续释放制剂施用,该持续释放制剂将使dsRNA在数天时间段内持续且一致地释放。本领域中熟知持续释放制剂。在这一实施方案中,剂量单位含有相应的多个日剂量。不管制剂如何,药物组合物中所含dsRNA的量都必须足以抑制所治疗的动物或人体内中靶基因表达的量。组合物的混配方式应使多个单位的dsRNA的总和一起含有足够剂量。
可以从细胞培养物测定和动物研究获得数据,以便制定适于人的剂量范围。本发明组合物的剂量应在包括ED50(通过已知方法测定)同时具有极小或无毒性的循环浓度的范围内。剂量可以根据所用剂型和所用施用途径而在此范围内变动。对于本发明方法中使用的化合物,治疗有效剂量最初可由细胞培养测定来估计。可以在动物模型中制定剂量,以达到包括如在细胞培养中测定的IC50(即,达到半数最大抑制的测试化合物的浓度)的化合物的循环血浆浓度范围。这些信息可用于更精确地确定适用于人的剂量。血浆中dsRNA的水平可以通过标准方法测量,例如高效液相色谱法。
药物组合物可以与施用说明一起被包含在试剂盒、容器、包装或分配器中。
治疗方法
本发明提供治疗有患全部或部分由KRAS(例如,KRAS转录物和/或KRas蛋白质水平的错误调控和/或升高)引起或可通过选择性靶向KRAS治疗的疾病或病症的风险(或易患该疾病或病症)的受试者的预防和治疗方法。
本文中使用的“治疗(treatment)”或“治疗(treating)”定义为对患有疾病或病症、具有疾病或病症的症状或者有发展疾病或病症倾向的患者应用或施用治疗剂(例如,DsiRNA试剂或载体或者编码其的转基因),或者对来自该患者的分离的组织或细胞系应用或施用治疗剂,以达到治疗、治愈、减轻、缓解、改变、补救、改善、改进或影响该疾病或病症、该疾病或病症的症状或患病倾向的目的。
一方面,本发明提供一种通过对受试者施用治疗剂(例如,DsiRNA试剂或载体或者编码其的转基因)来预防受试者的上述疾病或病症(包括例如通过抑制KRAS表达预防受试者体内转化事件的开始)的方法。有患疾病的风险的受试者可以例如通过本文所述诊断或预测测定中的一种或其组合来鉴别。预防剂可以在检测到受试者的(例如)癌症或者疾病或病症的症状特性表现之前施用,以预防该疾病或病症,或者延缓其发展。
本发明另一方面涉及治疗性治疗受试者的方法,即,改变疾病或病症的症状发作的方法。这些方法可以在体外(例如,通过将细胞与DsiRNA试剂一起培养)或在体内(例如,通过对受试者施用DsiRNA试剂)进行。
对于预防和治疗性治疗方法,这些治疗可以根据从药物基因组学领域获得的知识特别定制或修改的。本文中使用的“药物基因组学”是指应用基因组技术,例如对临床研究中和市场上的药物进行基因测序、统计遗传学和基因表达分析。更具体说来,该术语是指有关患者的基因如何确定其对药物的反应(例如,患者的“药物反应表型”或“药物反应基因型”)的研究。因此,本发明另一方面提供根据个体的药物反应基因型利用本发明的靶KRASRNA分子或靶KRAS RNA调节剂定制个体的预防性或治疗性治疗的方法。药物基因组学使得临床医生或医师能够将预防性或治疗性治疗靶向能从该治疗获得最大益处的患者,并且避免治疗将经历药物相关毒副作用的患者。
治疗剂可以在适当的动物模型中进行测试。例如,可以在动物模型中使用本文所述的DsiRNA试剂(或表达载体或编码其的转基因),以确定利用该药剂治疗的功效、毒性或副作用。或者,可以在动物模型中使用某一试剂(例如,治疗剂)以确定该试剂的作用机制。
用于评估KRAS mRNA水平和表达下调的模型
细胞培养
Kita等,1999,Int.J.Cancer,80,553-558描述了通过对突变KRAS基因特异的反义寡核苷酸抑制人胰腺癌细胞系生长。使用脂质体将反义寡核苷酸转染到经过转化的细胞。细胞增殖、KRAS mRNA表达和KRas蛋白质合成都评估为终点。Sato等,2000,CancerLett.,155,153-161描述了另一人胰腺癌细胞系HOR-P1,其以高血管生成活性和转移潜力为特征。对这一细胞系的遗传学和分子分析揭露出端粒酶活性增加和KRAS癌基因突变。
可以例如使用以下程序来测试本发明DsiRNA试剂的体内裂解活性。KRAScDNA内被本发明DsiRNA试剂靶向的核苷酸序列显示于上述KRAS序列中。
本发明的DsiRNA试剂可以使用HeLa细胞或其它哺乳动物细胞在细胞培养物中测试,以确定KRAS RNA和KRas蛋白质抑制的程度。选出针对本文所述KRAS靶的DsiRNA试剂(例如,参见图1和图4,以及上述结构)。在递送这些试剂后,通过适于例如培养的HeLa细胞或者其它转化或未转化的哺乳动物细胞的转染剂在培养物中测量KRAS RNA抑制。使用实时PCR扩增监测(例如ABI7700)相对于肌动蛋白或其它适当的对照物来测量靶KRASRNA的相对量。与针对不相关的靶,或针对具有相同总长度和化学结构但在每一位置随机取代的随机化DsiRNA对照物,或简单地针对适当的媒介物处理或未处理的对照物的寡核苷酸序列混合物进行比较。选出针对靶的初次和二次主导试剂,并进行优化。在选出最佳转染剂浓度后,利用主导DsiRNA分子进行RNA抑制过程。
mRNA的(实时PCR扩增监测)和Lightcycler定量
在递送DsiRNA后,例如使用用于大规模提取的Ambion Rnaqueous4-PCR纯化试剂盒或用于96孔测定的Ambion Rnaqueous-96纯化试剂盒,从细胞制备总RNA。对于Taqman分析,用例如在5'端共价连接的报告基团染料FAM或VIC和缀合至3'端的淬灭剂染料TAMARA合成双重标记的探针。在例如ABI PRISM7700序列检测器上,使用由10μL总RNA、100nM正向引物、100mM反向引物、100nM探针、1xTaqMan PCR反应缓冲液(PE-Applied Biosystems)、5.5mM MgCl2、各100μM的dATP、dCTP、dGTP和dTTP、0.2U RNase抑制剂(Promega)、0.025UAmpliTaq Gold(PE-Applied Biosystems)和0.2U M-MLV逆转录酶(Promega)组成的50μL反应物,进行一步RT-PCR扩增。热循环条件可由48℃下30分钟、95℃下10分钟,随后40个在95℃下15秒和60℃下1分钟的循环组成。靶KRAS mRNA水平的定量是相对于标准物而测定,该标准物由连续稀释的总细胞RNA(300、100、30、10ng/rxn)产生并针对例如在平行或相同管TaqMan反应中的36B4mRNA归一化的标准物测定。
蛋白质印迹
可以使用标准显微制备技术制备核提取物(参见例如,Andrews和Faller,1991,Nucleic Acids Research,19,2499)。来自上清液的蛋白质提取物是例如使用TCA沉淀法制备。将等体积的20%TCA加入细胞上清液中,在冰上孵育1小时,并通过离心5分钟使其沉淀。在丙酮中洗涤沉淀,干燥并再悬浮于水中。在10%Bis-Tris NuPage(核提取物)或4-12%Tris-甘氨酸(上清液提取物)聚丙烯酰胺凝胶上使细胞蛋白质提取物跑胶,并将其转移到硝化纤维素膜上。可以例如通过与5%脱脂乳孵育1小时,随后在4℃下与一抗孵育16小时来阻断非特异性结合。洗涤后,在室温下,应用(1:10,000稀释)二抗孵育例如1小时,并用SuperSignal试剂(Pierce)检测信号。
在几个细胞培养系统中,经显示,阳离子型脂质可增加培养物中细胞对寡核苷酸的生物利用率(Bennet,等,1992,Mol.Pharmacology,41,1023-1033)。在一个实施方案中,本发明的DsiRNA分子与阳离子型脂质形成复合物以用于细胞培养实验。DsiRNA和阳离子脂质混合物是在即将加入细胞之前于无血清DMEM中制备。使DMEM加添加物升温到室温(约20-25℃),并加入阳离子脂质达到最终所需浓度,且使溶液短时间涡旋。加入DsiRNA分子达到最终所需浓度,再次使溶液短时间涡旋,并在室温下孵育10分钟。在剂量反应实验中,在10分钟孵育后,RNA/脂质复合物被连续稀释于DMEM中。
动物模型
在动物模型中评估抗KRAS DsiRNA试剂的功效是进行人临床试验的重要前提。可使本领域中已知的癌症和/或增生性疾病、病况或病症的各种动物模型都适用于临床前评估本发明DsiRNA组合物对于治疗应用耳调节KRAS基因表达的功效。
与细胞培养物模型中的一样,最具Ras敏感性的小鼠肿瘤异种移植物是源自于表达突变Ras蛋白质的癌症细胞的异种移植物。携带有H-Ras转化的膀胱癌细胞异种移植物的裸小鼠对抗Ras反义核酸敏感,引起在31天治疗期后肿瘤生长的80%抑制(Wickstrom,2001,Mol.Biotechnol.,18,35-35)。Zhang等,2000,Gene Ther.,7,2041描述了靶向KRAS突变体(KRAS密码子12GGT变为GTT;分别为H441和H1725细胞)的抗KRAS核糖酶腺病毒载体(KRbz-ADV)。在裸小鼠异种移植物中使用表达突变KRas蛋白质的非小细胞肺癌细胞(NSCLC H441和H1725细胞),并与缺乏相关突变的NSCLC H1650细胞相比较。用KRbz-ADV预先治疗将完全消除H441和H1725细胞移植物,并与接受未治疗的肿瘤细胞或对照载体的动物中100%移植物和肿瘤生长形成对比。也已经描述了KRAS错误调控/突变的其它小鼠模型(例如,Kim等Cell121:823-835,其鉴别了KRAS在促进肺腺癌方面的作用)。上述研究证实,抗Ras试剂对Ras表达(例如,KRAS表达)的抑制引起动物中肿瘤生长的抑制。
因此,这些模型可用于评估本发明DsiRNA分子抑制KRAS水平、表达、肿瘤/癌症形成、生长、扩散、其它KRAS相关性表型、疾病或病症的发生等的功效。这些模型和其它模型可类似地用于在临床前环境中评估本发明DsiRNA分子的安全性/毒性和功效。
用于评估本发明的KRAS靶向性DsiRNA的动物模型系统的具体实例包括野生型小鼠、常位HCC异种移植物肿瘤模型小鼠(例如,Hep3B和HepG2)和弥散性黑色素瘤模型小鼠。在示例性体内实验中,以1至10mg/kg的剂量将本发明DsiRNA通过尾静脉注射到这些小鼠模型,或者以单剂量IC50水平施用重复剂量,并在施用最后一次剂量后24小时,采集器官(例如,肝、肾、肺、胰腺、结肠、皮肤、脾、骨髓、淋巴结、乳房脂肪垫等)。随后根据所用模型,评估这些器官中小鼠和/或人KRAS水平。也可以在最后一次施用DsiRNA后例如1、4、7、14、21或更多天检验作用持续时间。
除非另作指示,否则本发明的实践采用化学、分子生物学、微生物学、重组DNA、遗传学、免疫学、细胞生物学、细胞培养和转基因生物学常规技术,这些技术都在本领域技能范围内。参见例如,Maniatis等,1982,Molecular Cloning(Cold Spring HarborLaboratory Press,Cold Spring Harbor,N.Y.);Sambrook等,1989,Molecular Cloning,第2版(Cold Spring Harbor Laboratory Press,Cold Spring Harbor,N.Y.);Sambrook和Russell,2001,Molecular Cloning,第3版(Cold Spring Harbor Laboratory Press,ColdSpring Harbor,N.Y.);Ausubel等,1992),Current Protocols in Molecular Biology(John Wiley&Sons,包括定期更新);Glover,1985,DNA Cloning(IRL Press,Oxford);Anand,1992;Guthrie和Fink,1991;Harlow和Lane,1988,Antibodies,(Cold SpringHarbor Laboratory Press,Cold Spring Harbor,N.Y.);Jakoby和Pastan,1979;NucleicAcid Hybridization(B.D.Hames和S.J.Higgins编著,1984);Transcription AndTranslation(B.D.Hames和S.J.Higgins编著,1984);Culture Of Animal Cells(R.I.Freshney,Alan R.Liss,Inc.,1987);Immobilized Cells And Enzymes(IRL Press,1986);B.Perbal,A Practical Guide To Molecular Cloning(1984);Methods InEnzymology(Academic Press,Inc.,N.Y.);Gene Transfer Vectors For Mammaliancells(J.H.Miller和M.P.Calos编著,1987,Cold Spring Harbor Laboratory);MethodsIn Enzymology,第154和155卷(Wu等编著),Immunochemical Methods In Cell AndMolecular Biology(Mayer和Walker编著,Academic Press,London,1987);Handbook OfExperimental Immunology,第I-IV卷(D.M.Weir和C.C.Blackwell编著,1986);Riott,Essential Immunology,第6版,Blackwell Scientific Publications,Oxford,1988;Hogan等,Manipulating the Mouse Embryo,(Cold Spring Harbor Laboratory Press,Cold Spring Harbor,N.Y.,1986);Westerfield,M.,The zebrafish book.A guide forthe laboratory use of zebrafish(Danio rerio),(第4版,Univ.of Oregon Press,Eugene,2000)。
除非另作定义,否则本文中使用的所有科技术语都具有与本发明所属领域普通技术人员通常所了解的相同的含义。尽管与本文所述类似或相当的方法和材料可用于实行或测试本发明,但下文将描述适合的方法和物质。本文提到的所有出版物、专利申请、专利和其它参考文献的全文都以引用方式并入本文中。在出现矛盾的情况下,以本说明书(包括定义)为准。此外,这些材料、方法和实施例仅是说明性的,并不旨在限制。
实施例
本发明将参照以下实施例进行描述,这些实施例只是通过说明而提供,而不旨在以任何方式限制本发明。将利用本领域中熟知的标准技术或下文具体描述的技术。
实施例1:抗KRAS DsiRNA的设计
优选的抗KRAS DsiRNA试剂选自预先筛选的DsiRNA群。DsiRNA的设计可任选地涉及使用预测评分算法,这些算法执行跨序列区域的许多可能DsiRNA的预计活性/功效的计算机(in silico)评估。
实施例2:双链RNA寡核苷酸的制备
寡核苷酸的合成和纯化
DsiRNA分子可设计成与RNA信使(例如,本文所述RNA序列内的靶序列)中各个位点相互作用。在目前的示例性试剂中,选出两个靶KRAS序列。DsiRNA分子一条链的序列与上述靶KRAS位点序列互补。使用本文所述的方法化学合成DsiRNA分子。一般说来,使用关于19-23mer siRNA所述的固相寡核苷酸合成法来合成DsiRNA构建体(参见例如Usman等,美国专利No.5,804,683;No.5,831,071;No.5,998,203;No.6,117,657;No.6,353,098;No.6,362,323;No.6,437,117;No.6,469,158;Scaringe等,美国专利No.6,111,086;No.6,008,400;No.6,111,086)。
根据标准方法合成个别RNA链并借助HPLC纯化(Integrated DNA Technologies,Coralville,Iowa)。例如,使用固相亚磷胺化学法合成RNA寡核苷酸,使用标准技术去保护并在NAP-5柱(Amersham Pharmacia Biotech,Piscataway,N.J.)上脱盐(Damha和Olgivie,1993,Methods Mol Biol20:81-114;Wincott等,1995,Nucleic Acids Res23:2677-84)。使用离子交换高效液相色谱法(IE-HPLC),在Amersham Source15Q柱(1.0cm×25cm;AmershamPharmacia Biotech,Piscataway,N.J.)上使用15分钟的分级线性梯度纯化寡聚物。该梯度由90:10的缓冲液A:B变为52:48的缓冲液A:B,其中缓冲液A是100mM Tris pH8.5,且缓冲液B是100mM Tris pH8.5、1M NaCl。在260nm下监测样品,并收集对应于全长寡核苷酸种类的峰,汇集,在NAP-5柱上脱盐,并冻干。
通过毛细管电泳(CE),在Beckman PACE5000(Beckman Coulter,Inc.,Fullerton,Calif.)上测定每种寡聚物的纯度。CE毛细管的内径为100μm,并含有ssDNA100R凝胶(Beckman-Coulter)。通常,将约0.6nmol寡核苷酸注入毛细管中,在444V/cm电场下进行电泳,并在260nm下检测UV吸光度。变性Tris-硼酸盐-7M尿素电泳缓冲液是购自Beckman-Coulter。得到经CE测定纯度为至少90%的寡核糖核苷酸,以供用于下述实验中。根据制造商推荐的方案,在Voyager DE.TM Biospectometry Work Station(Applied Biosystems,Foster City,Calif.)上,通过基质辅助激光解吸电离飞行时间(MALDI-TOF)质谱法验证化合物的身份。获得所有寡聚物的相对分子质量,通常与预期分子质量的差异在0.2%范围内。
双链体的制备
将单链RNA(ssRNA)寡聚物以例如100μM的浓度再悬浮于由100mM乙酸钾、30mMHEPES(pH7.5)组成的双链体缓冲液中。以等摩尔量混合互补的有义链和反义链,以产生例如50μM双链体的最终溶液。在RNA缓冲液(IDT)中将样品加热到100℃,保持5分钟,并将其冷却到室温待用。在-20℃下储存双链RNA(dsRNA)寡聚物。将单链RNA寡聚物冻干储存或储存于-80℃的不含核酸酶的水中。
命名法
为保持一致,本说明书中采用以下命名法。提供给双链体的名称指示寡聚物的长度和突出的存在与否。“25/27”是具有25个碱基的有义链和27个碱基的反义链以及2个碱基的3'突出的不对称双链体。“27/25”是具有27个碱基的有义链和25个碱基的反义链的不对称双链体。
细胞培养和RNA转染
HeLa细胞是从ATCC获得,并在37℃和5%CO2下,维持在补充有10%胎牛血清(HyClone)的杜贝卡氏改良型伊格氏培养基(Dulbecco’s modified Eagle medium)(HyClone)中。对于RNA转染,使用LipofectamineTMRNAiMAX(Invitrogen)并遵循制造商的说明,用最终浓度为1nM或0.1nM的所述DsiRNA转染HeLa细胞。简言之,将2.5μL的0.2μM或0.02μMDsiRNA的储备液与46.5μL Opti-MEM I(Invitrogen)和1μL LipofectamineTMRNAiMAX混合。将得到的50μL混合物加入12孔板的各个孔中,并在室温下孵育20分钟,以形成DsiRNA:LipofectamineTMRNAiMAX复合物。同时,用胰蛋白酶水处理HeLa细胞,并以将其以367个细胞/μL的最终浓度再悬浮于培养基中。最后,将450μL细胞悬浮液加入各孔中(最终体积500μL),并将板放入培养箱中,培养24小时。
KRAS抑制的评估
通过qRT-PCR测定KRAS靶基因敲低,同时针对仅包括LipofectamineTMRNAiMAX(媒介物对照)的HPRT表达对照处理组或未处理组将值归一化。
RNA的分离和分析
用2mL PBS洗涤细胞一次,并使用RNeasy Mini KitTM(Qiagen)提取总RNA,并且洗脱得到30μL最终体积。遵循制造商的说明,使用Transcriptor1st Strand cDNA KitTM(Roche)和随机六聚物逆转录1μg的总RNA。将1/13的所得cDNA(0.66μL)与5μL IQMultiplex Powermix(Bio-Rad)以及3.33μL H2O和1μL3μM含有对人基因HPRT-1(登录号NM_000194)和KRAS靶序列特异的引物和探针的混合物混合。
定量RT-PCR
使用利用C1000热循环仪(Bio-Rad)的CFX96实时系统进行扩增反应。PCR条件是:95℃,保持3分钟;随后在95℃下10秒;在55℃下1分钟,循环40个循环。每一样品都以三个重复测试。将相对HPRT mRNA水平针对KRASmRNA水平归一化,并与在仅用转染试剂处理的对照样品或未处理样品中获得的mRNA水平相比较。使用Bio-Rad CFX Manager1.0版软件分析数据。
实施例3:靶向KRAS-355的DsiRNA对KRAS的抑制
如上文所述设计和合成靶向KRAS的DsiRNA分子,并在HeLa细胞中测试抑制功效。与相应针对KRAS靶序列的21mer siRNA相比较评估具有不同末端结构但都针对相同KRAScDNA靶序列(5’-AGCAGGTCAAGAGGAGTACAGTGCAAT-3’(SEQ ID NO:147))的DsiRNA试剂抑制KRAS表达的能力(有关所测试的抗KRAS试剂结构参看图1)。为进行这些实验,在转染前约24小时,将HeLa细胞以5,000-7,500个细胞/孔(100μl/孔)接种到96孔板中,因此在转染时,细胞达到70-90%汇合。对于转染,将退火的DsiRNA与转染试剂(LipofectamineTMRNAiMAX,Invitrogen)混合,体积为50μl/孔,并在室温下孵育20分钟。将DsiRNA转染混合物加入细胞,以达到1nM(图2)或100pM(图3)的最终DsiRNA浓度,体积为150μl。将各DsiRNA转染混合物加到3个孔中用于DsiRNA处理的三个重复。37℃下,在DsiRNA转染混合物持续存在下,将细胞孵育24小时。24小时时,由每一处理细胞的孔来制备RNA。首先取出含有转染混合物的上清液,并丢弃,然后裂解细胞,并由每一孔制备RNA。处理后,利用qRT-PCR针对KRAS靶基因评估靶KRAS RNA水平,并将值针对所得到的媒介物处理的对照物的值归一化。取三次重复数据的平均值,并测定每一处理的标准偏差。将归一化的数据绘图,并相比siRNA和媒介物或未处理的对照物确定活性DsiRNA使靶mRNA降低的倍数。
如图2所示,测试的25/27mer DsiRNA试剂(DP1148P/DP1151G)在1nM浓度下显示的KRAS抑制功效明显高于优化的21mer siRNA(DP1158P/DP1159GsiRNA),该优化的21mersiRNA(DP1158P/DP1159G siRNA)针对相同KRAS靶序列并在靶KRAS转录序列内共有与图1中测试的所有其它试剂相同的预计的Ago2裂解位点(所述Ago2裂解位点比对针对变异而标准化,这些变异可能以其它方式归因于RISC活性水平的改变)。值得注意的是,预计测试的25/27mer DsiRNA的Dicer酶裂解产生与所测试的“优化的”21mer完全相同的“优化的”21mersiRNA,且所得到的结果强调,DsiRNA试剂具有优于相应siRNA试剂的特殊功效/效力优势。与具有平端/平端和平端/断裂末端结构且类似地针对KRAS-355序列的21mer siRNA相比较,针对KRAS-355序列的27mer平端/平端和27mer平端/断裂的DsiRNA试剂在1nM浓度时观察到类似的明显结果。因此,与同时测试的相应21mer试剂相比较,测试的25/27mer和27merDsiRNA可重现地显示出增强的针对靶KRAS转录物的抑制功效。事实上,测试的所有25/27mer和27mer DsiRNA在1nM浓度下都意外地优于相同浓度的测试的所有21mer siRNA。
100pM浓度时抗KRAS-355DsiRNA试剂也观察到稳固的抑制功效(图3)。测试的25/27mer DsiRNA试剂(DP1148P/DP1151G)在100pM浓度时的KRAS抑制功效明显高于针对相同KRAS-355靶序列的优化的21mer siRNA(DP1158P/DP1159G siRNA)。与具有平端/断裂的末端结构的相应21mer siRNA相比较,针对KRAS-355序列的27mer平端/断裂的DsiRNA试剂在100pM浓度时观察到类似的明显结果。27mer平端/平端试剂与测试的相应21mer平端/平端试剂至少同样有效,即使27mer平端/平端试剂的功效相对于21mer平端/平端试剂的功效的明显增强在100pM浓度时不具有统计学显著性。因此,在100pM下,测试的25/27mer和27mer平端/断裂的DsiRNA可重现地表现相比同时测试的相应21mer siRNA试剂有所增强的针对靶KRAS转录物的抑制功效。
实施例4:靶向KRAS-940的DsiRNA对KRAS的抑制
如上文所述设计和合成靶向KRAS的DsiRNA分子,并如实施例3中所述在HeLa细胞中测试抑制功效。与相应针对KRAS靶序列的21mer siRNA相比较评估具有不同末端结构但都针对相同KRAS cDNA靶序列(5’-TATTAGCATTTGTTTTAGCATTACCTA-3’(SEQ ID NO:179))的DsiRNA试剂抑制KRAS表达的能力(有关所测试的抗KRAS试剂结构参看图4)。如图5所示,测试的25/27mer DsiRNA试剂(DP1136P/DP1139G)在1nM浓度时显示的KRAS抑制功效明显高于的优化的21mer siRNA(DP1146P/DP1147G siRNA),该优化的21mer siRNA(DP1146P/DP1147G siRNA)针对相同KRAS靶序列并在靶KRAS转录序列内共有与图4中测试的所有其它试剂相同的预计的Ago2裂解位点(所述Ago2裂解位点比对针对变异而标准化,这些变异可能以其它方式归因于RISC活性水平的改变)。值得注意的是,预计测试的25/27mer DsiRNA的Dicer酶裂解产生与所测试的“优化的”21mer完全相同的“优化的”21mer siRNA,且所得到的结果强调,DsiRNA试剂具有优于相应siRNA试剂的特殊功效/效力优势。与具有平端/平端和平端/断裂末端结构且类似地针对KRAS-940序列的21mer siRNA相比较,针对KRAS-940序列的27mer平端/平端和27mer平端/断裂的DsiRNA试剂在1nM浓度时观察到类似的明显结果。因此,与同时测试的相应21mer试剂相比较,测试的25/27mer和27mer DsiRNA可重现地显示出增强的针对靶KRAS转录物的抑制功效。事实上,测试的所有25/27mer和27merDsiRNA在1nM浓度时都意外地优于相同浓度的测试的所有21mer siRNA。
100pM浓度时的抗KRAS-940DsiRNA试剂也观察到稳固的抑制功效(图6)。测试的25/27mer DsiRNA试剂(DP1136P/DP1139G)在100pM浓度时显示KRAS抑制功效明显高于针对相同KRAS-940靶序列的优化的21mer siRNA(DP1146P/DP1147G siRNA)。与具有平端/断裂的末端结构的相应21mer siRNA相比较,针对KRAS-940序列的27mer平端/断裂的DsiRNA试剂在100pM浓度时观察到类似的明显结果。因此,在100pM时,与同时测试的相应21mersiRNA试剂相比较,测试的25/27mer和27mer平端/断裂的DsiRNA可重现地表现增强的针对靶KRAS转录物的抑制功效。事实上,测试的所有抗KRAS-94025/27mer和27mer DsiRNA在100pM浓度时都意外地优于相同浓度的测试的所有21mer siRNA。
实施例5:其它DsiRNA对KRAS的抑制
如上文所述设计和合成表3中所示具有反义链SEQ ID NO:11-50并靶向KRAS野生型序列的40个DsiRNA分子(未测试表3中靶向替代性/多态性序列的DsiRNA),并如上文实施例3中所述在HeLa细胞中测试抑制功效。与相应针对KRAS靶序列的21mer siRNA相比较评估这些DsiRNA试剂抑制KRAS表达的能力(有关测试的相应抗KRAS21mer试剂反义链,参看表2;且有关实验的示意图参看图7)。所有DsiRNA试剂都显示作为KRAS抑制剂的功效,其中测试的40种DsiRNA试剂中有35种显示KRAS靶降低超过50%。如图8中所示,对于每5个测试的DsiRNA同源性siRNA对中的4对,DsiRNA试剂在降低KRAS靶水平方面表现显著优于同源siRNA试剂的优越的功效。利用1nM和5nM测试浓度,在施用后24小时和48小时都检验这种抑制作用的持续时间。对于40个DsiRNA同源性siRNA对中的26对,在所有测试浓度和持续时间下,DsiRNA试剂显示出比相应同源siRNA试剂在统计学显著增强的KRAS靶抑制作用水平(图9)。这一结果与40种中仅6种其中同源siRNA试剂优于DsiRNA试剂的情形形成鲜明对比(图9)。因此,DsiRNA与相配的同源siRNA(具有对准的预计Ago2裂解位点)对于KRAS靶RNA的抑制作用存在统计学显著差异。在很大程度上,DsiRNA明显且意外地优于同源siRNA。重要的是,这些结果证实,DsiRNA的活性与siRNA活性不直接相关,也不是保持相反。因此,上述结果证实,DsiRNA和siRNA以不同方式结合RNA干扰机构,并且DsiRNA和siRNA尽管都包含双链RNA,但事实上是不同的药物。
如图10和图11所示,测定这40种KRAS靶向性不对称DsiRNA中29种的IC50值。很明显,这29种不对称DsiRNA中有5种的IC50值低于10pM,进一步证明这些DsiRNA的明显效力。
实施例6:243种所选KRAS靶向性DsiRNA的KRAS抑制的测定
在本实施例中,构造243种不对称DsiRNA(此处,如上文所述测试的DsiRNA具有25/27mer结构),并在1nM浓度这些DsiRNA存在下孵育的人HeLa细胞和小鼠Hepa1-6细胞中测试KRAS抑制功效。测试的243种不对称DsiRNA包括选自上表2-5的一小组DsiRNA,以及设计成靶向人KRAS、小鼠KRAS或二者内的特定序列的另一组不对称DsiRNA。这243种不对称DsiRNA的序列和结构显示于表8中。
表8:在人HeLa细胞和小鼠Hepa1-6细胞中测试的其它抗KRAS不对称(25/27mer)DsiRNA试剂的结构
5'-GAGGCCUGCUGAAAAUGACUGAAta-3'(SEQ ID NO:4650)
3'-CUCUCCGGACGACUUUUACUGACUUAU-5'(SEQ ID NO:4407)
KRAS-166靶:5'-GAGAGGCCTGCTGAAAATGACTGAATA-3'(SEQ ID NO:4893)
5'-AGGCCUGCUGAAAAUGACUGAAUat-3'(SEQ ID NO:4651)
3'-UCUCCGGACGACUUUUACUGACUUAUA-5'(SEQ ID NO:4408)
KRAS-167靶:5'-AGAGGCCTGCTGAAAATGACTGAATAT-3'(SEQ ID NO:4894)
5'-GGCCUGCUGAAAAUGACUGAAUAta-3'(SEQ ID NO:4652)
3'-CUCCGGACGACUUUUACUGACUUAUAU-5'(SEQ ID NO:4409)
KRAS-168靶:5'-GAGGCCTGCTGAAAATGACTGAATATA-3'(SEQ ID NO:4895)
5'-GCCUGCUGAAAAUGACUGAAUAUaa-3'(SEQ ID NO:4653)
3'-UCCGGACGACUUUUACUGACUUAUAUU-5'(SEQ ID NO:4410)
KRAS-169靶:5'-AGGCCTGCTGAAAATGACTGAATATAA-3'(SEQ ID NO:4896)
5'-GUUGGAGCUGGUGGCGUAGGCAAga-3'(SEQ ID NO:4654)
3'-AUCAACCUCGACCACCGCAUCCGUUCU-5'(SEQ ID NO:4411)
KRAS-204靶:5'-TAGTTGGAGCTGGTGGCGTAGGCAAGA-3'(SEQ ID NO:4897)
5'-UUGGAGCUGGUGGCGUAGGCAAGag-3'(SEQ ID NO:4655)
3'-UCAACCUCGACCACCGCAUCCGUUCUC-5'(SEQ ID NO:4412)
KRAS-205靶:5'-AGTTGGAGCTGGTGGCGTAGGCAAGAG-3'(SEQ ID NO:4898)
5'-UGGAGCUGGUGGCGUAGGCAAGAgt-3'(SEQ ID NO:4656)
3'-CAACCUCGACCACCGCAUCCGUUCUCA-5'(SEQ ID NO:4413)
KRAS-206靶:5'-GTTGGAGCTGGTGGCGTAGGCAAGAGT-3'(SEQ ID NO:4899)
5'-GGAGCUGGUGGCGUAGGCAAGAGtg-3'(SEQ ID NO:4657)
3'-AACCUCGACCACCGCAUCCGUUCUCAC-5'(SEQ ID NO:4414)
KRAS-207靶:5'-TTGGAGCTGGTGGCGTAGGCAAGAGTG-3'(SEQ ID NO:4900)
5'-GAGCUGGUGGCGUAGGCAAGAGUgc-3'(SEQ ID NO:4658)
3'-ACCUCGACCACCGCAUCCGUUCUCACG-5'(SEQ ID NO:4415)
KRAS-208靶:5'-TGGAGCTGGTGGCGTAGGCAAGAGTGC-3'(SEQ ID NO:4901)
5'-AGCUGGUGGCGUAGGCAAGAGUGcc-3'(SEQ ID NO:4659)
3'-CCUCGACCACCGCAUCCGUUCUCACGG-5'(SEQ ID NO:4416)
KRAS-209靶:5'-GGAGCTGGTGGCGTAGGCAAGAGTGCC-3'(SEQ ID NO:4902)
5'-GCUGGUGGCGUAGGCAAGAGUGCct-3'(SEQ ID NO:4660)
3'-CUCGACCACCGCAUCCGUUCUCACGGA-5'(SEQ ID NO:4417)
KRAS-210靶:5'-GAGCTGGTGGCGTAGGCAAGAGTGCCT-3'(SEQ ID NO:4903)
5'-UACAGCUAAUUCAGAAUCAUUUUgt-3'(SEQ ID NO:4661)
3'-CUAUGUCGAUUAAGUCUUAGUAAAACA-5'(SEQ ID NO:4418)
KRAS-241靶:5'-GATACAGCTAATTCAGAATCATTTTGT-3'(SEQ ID NO:4904)
5'-UAAUUGAUGGAGAAACCUGUCUCtt-3'(SEQ ID NO:4662)
3'-UCAUUAACUACCUCUUUGGACAGAGAA-5'(SEQ ID NO:4419)
KRAS-313靶:5'-AGTAATTGATGGAGAAACCTGTCTCTT-3'(SEQ ID NO:4905)
5'-AAUUGAUGGAGAAACCUGUCUCUtg-3'(SEQ ID NO:4663)
3'-CAUUAACUACCUCUUUGGACAGAGAAC-5'(SEQ ID NO:4420)
KRAS-314靶:5'-GTAATTGATGGAGAAACCTGTCTCTTG-3'(SEQ ID NO:4906)
5'-GAUGGAGAAACCUGUCUCUUGGAta-3'(SEQ ID NO:4664)
3'-AACUACCUCUUUGGACAGAGAACCUAU-5'(SEQ ID NO:4421)
KRAS-318靶:5'-TTGATGGAGAAACCTGTCTCTTGGATA-3'(SEQ ID NO:4907)
5'-CCUGUCUCUUGGAUAUUCUCGACac-3'(SEQ ID NO:4665)
3'-UUGGACAGAGAACCUAUAAGAGCUGUG-5'(SEQ ID NO:4422)
KRAS-328靶:5'-AACCTGTCTCTTGGATATTCTCGACAC-3'(SEQ ID NO:4908)
5'-UGUCUCUUGGAUAUUCUCGACACag-3'(SEQ ID NO:4666)
3'-GGACAGAGAACCUAUAAGAGCUGUGUC-5'(SEQ ID NO:4423)
KRAS-330靶:5'-CCTGTCTCTTGGATATTCTCGACACAG-3'(SEQ ID NO:4909)
5'-GUCUCUUGGAUAUUCUCGACACAgc-3'(SEQ ID NO:4667)
3'-GACAGAGAACCUAUAAGAGCUGUGUCG-5'(SEQ ID NO:4424)
KRAS-331靶:5'-CTGTCTCTTGGATATTCTCGACACAGC-3'(SEQ ID NO:4910)
5'-UCUCUUGGAUAUUCUCGACACAGca-3'(SEQ ID NO:4668)
3'-ACAGAGAACCUAUAAGAGCUGUGUCGU-5'(SEQ ID NO:4425)
KRAS-332靶:5'-TGTCTCTTGGATATTCTCGACACAGCA-3'(SEQ ID NO:4911)
5'-CUCUUGGAUAUUCUCGACACAGCag-3'(SEQ ID NO:4669)
3'-CAGAGAACCUAUAAGAGCUGUGUCGUC-5'(SEQ ID NO:4426)
KRAS-333靶:5'-GTCTCTTGGATATTCTCGACACAGCAG-3'(SEQ ID NO:4912)
5'-UCUUGGAUAUUCUCGACACAGCAgg-3'(SEQ ID NO:4670)
3'-AGAGAACCUAUAAGAGCUGUGUCGUCC-5'(SEQ ID NO:4427)
KRAS-334靶:5'-TCTCTTGGATATTCTCGACACAGCAGG-3'(SEQ ID NO:4913)
5'-CUUGGAUAUUCUCGACACAGCAGgt-3'(SEQ ID NO:4671)
3'-GAGAACCUAUAAGAGCUGUGUCGUCCA-5'(SEQ ID NO:4428)
KRAS-335靶:5'-CTCTTGGATATTCTCGACACAGCAGGT-3'(SEQ ID NO:4914)
5'-UUGGAUAUUCUCGACACAGCAGGtc-3'(SEQ ID NO:4672)
3'-AGAACCUAUAAGAGCUGUGUCGUCCAG-5'(SEQ ID NO:4429)
KRAS-336靶:5'-TCTTGGATATTCTCGACACAGCAGGTC-3'(SEQ ID NO:4915)
5'-CAGCAGGUCAAGAGGAGUACAGUgc-3'(SEQ ID NO:4673)
3'-GUGUCGUCCAGUUCUCCUCAUGUCACG-5'(SEQ ID NO:4430)
KRAS-352靶:5'-CACAGCAGGTCAAGAGGAGTACAGTGC-3'(SEQ ID NO:4916)
5'-AGCAGGUCAAGAGGAGUACAGUGca-3'(SEQ ID NO:4674)
3'-UGUCGUCCAGUUCUCCUCAUGUCACGU-5'(SEQ ID NO:4431)
KRAS-353靶:5'-ACAGCAGGTCAAGAGGAGTACAGTGCA-3'(SEQ ID NO:4917)
5'-GCAGGUCAAGAGGAGUACAGUGCaa-3'(SEQ ID NO:4675)
3'-GUCGUCCAGUUCUCCUCAUGUCACGUU-5'(SEQ ID NO:4432)
KRAS-354靶:5'-CAGCAGGTCAAGAGGAGTACAGTGCAA-3'(SEQ ID NO:4918)
5'-AGGAGUACAGUGCAAUGAGGGACca-3'(SEQ ID NO:4676)
3'-UCUCCUCAUGUCACGUUACUCCCUGGU-5'(SEQ ID NO:4433)
KRAS-364靶:5'-AGAGGAGTACAGTGCAATGAGGGACCA-3'(SEQ ID NO:4919)
5'-GGAGUACAGUGCAAUGAGGGACCag-3'(SEQ ID NO:4677)
3'-CUCCUCAUGUCACGUUACUCCCUGGUC-5'(SEQ ID NO:4434)
KRAS-365靶:5'-GAGGAGTACAGTGCAATGAGGGACCAG-3'(SEQ ID NO:4920)
5'-GAGUACAGUGCAAUGAGGGACCAgt-3'(SEQ ID NO:4678)
3'-UCCUCAUGUCACGUUACUCCCUGGUCA-5'(SEQ ID NO:4435)
KRAS-366靶:5'-AGGAGTACAGTGCAATGAGGGACCAGT-3'(SEQ ID NO:4921)
5'-AGUACAGUGCAAUGAGGGACCAGta-3'(SEQ ID NO:4679)
3'-CCUCAUGUCACGUUACUCCCUGGUCAU-5'(SEQ ID NO:4436)
KRAS-367靶:5'-GGAGTACAGTGCAATGAGGGACCAGTA-3'(SEQ ID NO:4922)
5'-GUACAGUGCAAUGAGGGACCAGUac-3'(SEQ ID NO:4680)
3'-CUCAUGUCACGUUACUCCCUGGUCAUG-5'(SEQ ID NO:4437)
KRAS-368靶:5'-GAGTACAGTGCAATGAGGGACCAGTAC-3'(SEQ ID NO:4923)
5'-UACAGUGCAAUGAGGGACCAGUAca-3'(SEQ ID NO:4681)
3'-UCAUGUCACGUUACUCCCUGGUCAUGU-5'(SEQ ID NO:4438)
KRAS-369靶:5'-AGTACAGTGCAATGAGGGACCAGTACA-3'(SEQ ID NO:4924)
5'-ACAGUGCAAUGAGGGACCAGUACat-3'(SEQ ID NO:4682)
3'-CAUGUCACGUUACUCCCUGGUCAUGUA-5'(SEQ ID NO:4439)
KRAS-370靶:5'-GTACAGTGCAATGAGGGACCAGTACAT-3'(SEQ ID NO:4925)
5'-CAGUGCAAUGAGGGACCAGUACAtg-3'(SEQ ID NO:4683)
3'-AUGUCACGUUACUCCCUGGUCAUGUAC-5'(SEQ ID NO:4440)
KRAS-371靶:5'-TACAGTGCAATGAGGGACCAGTACATG-3'(SEQ ID NO:4926)
5'-AGUGCAAUGAGGGACCAGUACAUga-3'(SEQ ID NO:4684)
3'-UGUCACGUUACUCCCUGGUCAUGUACU-5'(SEQ ID NO:4441)
KRAS-372靶:5'-ACAGTGCAATGAGGGACCAGTACATGA-3'(SEQ ID NO:4927)
5'-GUAUUUGCCAUAAAUAAUACUAAat-3'(SEQ ID NO:4685)
3'-CACAUAAACGGUAUUUAUUAUGAUUUA-5'(SEQ ID NO:4442)
KRAS-420靶:5'-GTGTATTTGCCATAAATAATACTAAAT-3'(SEQ ID NO:4928)
5'-UAUUUGCCAUAAAUAAUACUAAAtc-3'(SEQ ID NO:4686)
3'-ACAUAAACGGUAUUUAUUAUGAUUUAG-5'(SEQ ID NO:4443)
KRAS-421靶:5'-TGTATTTGCCATAAATAATACTAAATC-3'(SEQ ID NO:4929)
5'-AUUUGCCAUAAAUAAUACUAAAUca-3'(SEQ ID NO:4687)
3'-CAUAAACGGUAUUUAUUAUGAUUUAGU-5'(SEQ ID NO:4444)
KRAS-422靶:5'-GTATTTGCCATAAATAATACTAAATCA-3'(SEQ ID NO:4930)
5'-UUUGCCAUAAAUAAUACUAAAUCat-3'(SEQ ID NO:4688)
3'-AUAAACGGUAUUUAUUAUGAUUUAGUA-5'(SEQ ID NO:4445)
KRAS-423靶:5'-TATTTGCCATAAATAATACTAAATCAT-3'(SEQ ID NO:4931)
5'-UUGCCAUAAAUAAUACUAAAUCAtt-3'(SEQ ID NO:4689)
3'-UAAACGGUAUUUAUUAUGAUUUAGUAA-5'(SEQ ID NO:4446)
KRAS-424靶:5'-ATTTGCCATAAATAATACTAAATCATT-3'(SEQ ID NO:4932)
5'-UGCCAUAAAUAAUACUAAAUCAUtt-3'(SEQ ID NO:4690)
3'-AAACGGUAUUUAUUAUGAUUUAGUAAA-5'(SEQ ID NO:4447)
KRAS-425靶:5'-TTTGCCATAAATAATACTAAATCATTT-3'(SEQ ID NO:4933)
5'-GCCAUAAAUAAUACUAAAUCAUUtg-3'(SEQ ID NO:4691)
3'-AACGGUAUUUAUUAUGAUUUAGUAAAC-5'(SEQ ID NO:4448)
KRAS-426靶:5'-TTGCCATAAATAATACTAAATCATTTG-3'(SEQ ID NO:4934)
5'-AUACUAAAUCAUUUGAAGAUAUUca-3'(SEQ ID NO:4692)
3'-AUUAUGAUUUAGUAAACUUCUAUAAGU-5'(SEQ ID NO:4449)
KRAS-436靶:5'-TAATACTAAATCATTTGAAGATATTCA-3'(SEQ ID NO:4935)
5'-UACUAAAUCAUUUGAAGAUAUUCac-3'(SEQ ID NO:4693)
3'-UUAUGAUUUAGUAAACUUCUAUAAGUG-5'(SEQ ID NO:4450)
KRAS-437靶:5'-AATACTAAATCATTTGAAGATATTCAC-3'(SEQ ID NO:4936)
5'-ACUAAAUCAUUUGAAGAUAUUCAcc-3'(SEQ ID NO:4694)
3'-UAUGAUUUAGUAAACUUCUAUAAGUGG-5'(SEQ ID NO:4451)
KRAS-438靶:5'-ATACTAAATCATTTGAAGATATTCACC-3'(SEQ ID NO:4937)
5'-CUAAAUCAUUUGAAGAUAUUCACca-3'(SEQ ID NO:4695)
3'-AUGAUUUAGUAAACUUCUAUAAGUGGU-5'(SEQ ID NO:4452)
KRAS-439靶:5'-TACTAAATCATTTGAAGATATTCACCA-3'(SEQ ID NO:4938)
5'-UAAAUCAUUUGAAGAUAUUCACCat-3'(SEQ ID NO:4696)
3'-UGAUUUAGUAAACUUCUAUAAGUGGUA-5'(SEQ ID NO:4453)
KRAS-440靶:5'-ACTAAATCATTTGAAGATATTCACCAT-3'(SEQ ID NO:4939)
5'-AAAUCAUUUGAAGAUAUUCACCAtt-3'(SEQ ID NO:4697)
3'-GAUUUAGUAAACUUCUAUAAGUGGUAA-5'(SEQ ID NO:4454)
KRAS-441靶:5'-CTAAATCATTTGAAGATATTCACCATT-3'(SEQ ID NO:4940)
5'-AAUCAUUUGAAGAUAUUCACCAUta-3'(SEQ ID NO:4698)
3'-AUUUAGUAAACUUCUAUAAGUGGUAAU-5'(SEQ ID NO:4455)
KRAS-442靶:5'-TAAATCATTTGAAGATATTCACCATTA-3'(SEQ ID NO:4941)
5'-AUCAUUUGAAGAUAUUCACCAUUat-3'(SEQ ID NO:4699)
3'-UUUAGUAAACUUCUAUAAGUGGUAAUA-5'(SEQ ID NO:4456)
KRAS-443靶:5'-AAATCATTTGAAGATATTCACCATTAT-3'(SEQ ID NO:4942)
5'-UCAUUUGAAGAUAUUCACCAUUAta-3'(SEQ ID NO:4700)
3'-UUAGUAAACUUCUAUAAGUGGUAAUAU-5'(SEQ ID NO:4457)
KRAS-444靶:5'-AATCATTTGAAGATATTCACCATTATA-3'(SEQ ID NO:4943)
5'-AUAUUCACCAUUAUAGAGAACAAat-3'(SEQ ID NO:4701)
3'-UCUAUAAGUGGUAAUAUCUCUUGUUUA-5'(SEQ ID NO:4458)
KRAS-454靶:5'-AGATATTCACCATTATAGAGAACAAAT-3'(SEQ ID NO:4944)
5'-UAUUCACCAUUAUAGAGAACAAAtt-3'(SEQ ID NO:4702)
3'-CUAUAAGUGGUAAUAUCUCUUGUUUAA-5'(SEQ ID NO:4459)
KRAS-455靶:5'-GATATTCACCATTATAGAGAACAAATT-3'(SEQ ID NO:4945)
5'-AUUCACCAUUAUAGAGAACAAAUta-3'(SEQ ID NO:4703)
3'-UAUAAGUGGUAAUAUCUCUUGUUUAAU-5'(SEQ ID NO:4460)
KRAS-456靶:5'-ATATTCACCATTATAGAGAACAAATTA-3'(SEQ ID NO:4946)
5'-UUCACCAUUAUAGAGAACAAAUUaa-3'(SEQ ID NO:4704)
3'-AUAAGUGGUAAUAUCUCUUGUUUAAUU-5'(SEQ ID NO:4461)
KRAS-457靶:5'-TATTCACCATTATAGAGAACAAATTAA-3'(SEQ ID NO:4947)
5'-UCACCAUUAUAGAGAACAAAUUAaa-3'(SEQ ID NO:4705)
3'-UAAGUGGUAAUAUCUCUUGUUUAAUUU-5'(SEQ ID NO:4462)
KRAS-458靶:5'-ATTCACCATTATAGAGAACAAATTAAA-3'(SEQ ID NO:4948)
5'-CACCAUUAUAGAGAACAAAUUAAaa-3'(SEQ ID NO:4706)
3'-AAGUGGUAAUAUCUCUUGUUUAAUUUU-5'(SEQ ID NO:4463)
KRAS-459靶:5'-TTCACCATTATAGAGAACAAATTAAAA-3'(SEQ ID NO:4949)
5'-ACCAUUAUAGAGAACAAAUUAAAag-3'(SEQ ID NO:4707)
3'-AGUGGUAAUAUCUCUUGUUUAAUUUUC-5'(SEQ ID NO:4464)
KRAS-460靶:5'-TCACCATTATAGAGAACAAATTAAAAG-3'(SEQ ID NO:4950)
5'-CCAUUAUAGAGAACAAAUUAAAAga-3'(SEQ ID NO:4708)
3'-GUGGUAAUAUCUCUUGUUUAAUUUUCU-5'(SEQ ID NO:4465)
KRAS-461靶:5'-CACCATTATAGAGAACAAATTAAAAGA-3'(SEQ ID NO:4951)
5'-CAUUAUAGAGAACAAAUUAAAAGag-3'(SEQ ID NO:4709)
3'-UGGUAAUAUCUCUUGUUUAAUUUUCUC-5'(SEQ ID NO:4466)
KRAS-462靶:5'-ACCATTATAGAGAACAAATTAAAAGAG-3'(SEQ ID NO:4952)
5'-CUAUGGUCCUAGUAGGAAAUAAAtg-3'(SEQ ID NO:4710)
3'-UGGAUACCAGGAUCAUCCUUUAUUUAC-5'(SEQ ID NO:4467)
KRAS-508靶:5'-ACCTATGGTCCTAGTAGGAAATAAATG-3'(SEQ ID NO:4953)
5'-UGUGAUUUGCCUUCUAGAACAGUag-3'(SEQ ID NO:4711)
3'-UUACACUAAACGGAAGAUCUUGUCAUC-5'(SEQ ID NO:4468)
KRAS-531靶:5'-AATGTGATTTGCCTTCTAGAACAGTAG-3'(SEQ ID NO:4954)
5'-GUGAUUUGCCUUCUAGAACAGUAga-3'(SEQ ID NO:4712)
3'-UACACUAAACGGAAGAUCUUGUCAUCU-5'(SEQ ID NO:4469)
KRAS-532靶:5'-ATGTGATTTGCCTTCTAGAACAGTAGA-3'(SEQ ID NO:4955)
5'-GAUUUGCCUUCUAGAACAGUAGAca-3'(SEQ ID NO:4713)
3'-CACUAAACGGAAGAUCUUGUCAUCUGU-5'(SEQ ID NO:4470)
KRAS-534靶:5'-GTGATTTGCCTTCTAGAACAGTAGACA-3'(SEQ ID NO:4956)
5'-GUUAUGGAAUUCCUUUUAUUGAAac-3'(SEQ ID NO:4714)
3'-UUCAAUACCUUAAGGAAAAUAACUUUG-5'(SEQ ID NO:4471)
KRAS-586靶:5'-AAGTTATGGAATTCCTTTTATTGAAAC-3'(SEQ ID NO:4957)
5'-UUAUGGAAUUCCUUUUAUUGAAAca-3'(SEQ ID NO:4715)
3'-UCAAUACCUUAAGGAAAAUAACUUUGU-5'(SEQ ID NO:4472)
KRAS-587靶:5'-AGTTATGGAATTCCTTTTATTGAAACA-3'(SEQ ID NO:4958)
5'-UAUGGAAUUCCUUUUAUUGAAACat-3'(SEQ ID NO:4716)
3'-CAAUACCUUAAGGAAAAUAACUUUGUA-5'(SEQ ID NO:4473)
KRAS-588靶:5'-GTTATGGAATTCCTTTTATTGAAACAT-3'(SEQ ID NO:4959)
5'-GAUGCCUUCUAUACAUUAGUUCGag-3'(SEQ ID NO:4717)
3'-UACUACGGAAGAUAUGUAAUCAAGCUC-5'(SEQ ID NO:4474)
KRAS-763靶:5'-ATGATGCCTTCTATACATTAGTTCGAG-3'(SEQ ID NO:4960)
5'-AUGCCUUCUAUACAUUAGUUCGAga-3'(SEQ ID NO:4718)
3'-ACUACGGAAGAUAUGUAAUCAAGCUCU-5'(SEQ ID NO:4475)
KRAS-764靶:5'-TGATGCCTTCTATACATTAGTTCGAGA-3'(SEQ ID NO:4961)
5'-CGAGAAAUUCGAAAACAUAAAGAaa-3'(SEQ ID NO:4719)
3'-AAGCUCUUUAAGCUUUUGUAUUUCUUU-5'(SEQ ID NO:4476)
KRAS-784靶:5'-TTCGAGAAATTCGAAAACATAAAGAAA-3'(SEQ ID NO:4962)
5'-GAAAACAUAAAGAAAAGAUGAGCaa-3'(SEQ ID NO:4720)
3'-AGCUUUUGUAUUUCUUUUCUACUCGUU-5'(SEQ ID NO:4477)
KRAS-794靶:5'-TCGAAAACATAAAGAAAAGATGAGCAA-3'(SEQ ID NO:4963)
5'-AAAACAUAAAGAAAAGAUGAGCAaa-3'(SEQ ID NO:4721)
3'-GCUUUUGUAUUUCUUUUCUACUCGUUU-5'(SEQ ID NO:4478)
KRAS-795靶:5'-CGAAAACATAAAGAAAAGATGAGCAAA-3'(SEQ ID NO:4964)
5'-AAACAUAAAGAAAAGAUGAGCAAag-3'(SEQ ID NO:4722)
3'-CUUUUGUAUUUCUUUUCUACUCGUUUC-5'(SEQ ID NO:4479)
KRAS-796靶:5'-GAAAACATAAAGAAAAGATGAGCAAAG-3'(SEQ ID NO:4965)
5'-AACAUAAAGAAAAGAUGAGCAAAga-3'(SEQ ID NO:4723)
3'-UUUUGUAUUUCUUUUCUACUCGUUUCU-5'(SEQ ID NO:4480)
KRAS-797靶:5'-AAAACATAAAGAAAAGATGAGCAAAGA-3'(SEQ ID NO:4966)
5'-ACAUAAAGAAAAGAUGAGCAAAGat-3'(SEQ ID NO:4724)
3'-UUUGUAUUUCUUUUCUACUCGUUUCUA-5'(SEQ ID NO:4481)
KRAS-798靶:5'-AAACATAAAGAAAAGATGAGCAAAGAT-3'(SEQ ID NO:4967)
5'-CAUAAAGAAAAGAUGAGCAAAGAtg-3'(SEQ ID NO:4725)
3'-UUGUAUUUCUUUUCUACUCGUUUCUAC-5'(SEQ ID NO:4482)
KRAS-799靶:5'-AACATAAAGAAAAGATGAGCAAAGATG-3'(SEQ ID NO:4968)
5'-AUAAAGAAAAGAUGAGCAAAGAUgg-3'(SEQ ID NO:4726)
3'-UGUAUUUCUUUUCUACUCGUUUCUACC-5'(SEQ ID NO:4483)
KRAS-800靶:5'-ACATAAAGAAAAGATGAGCAAAGATGG-3'(SEQ ID NO:4969)
5'-UAAAGAAAAGAUGAGCAAAGAUGgt-3'(SEQ ID NO:4727)
3'-GUAUUUCUUUUCUACUCGUUUCUACCA-5'(SEQ ID NO:4484)
KRAS-801靶:5'-CATAAAGAAAAGATGAGCAAAGATGGT-3'(SEQ ID NO:4970)
5'-AAAGAAAAGAUGAGCAAAGAUGGta-3'(SEQ ID NO:4728)
3'-UAUUUCUUUUCUACUCGUUUCUACCAU-5'(SEQ ID NO:4485)
KRAS-802靶:5'-ATAAAGAAAAGATGAGCAAAGATGGTA-3'(SEQ ID NO:4971)
5'-AAGUGGUAAUUUUUGUACAUUACac-3'(SEQ ID NO:4729)
3'-UGUUCACCAUUAAAAACAUGUAAUGUG-5'(SEQ ID NO:4486)
KRAS-908靶:5'-ACAAGTGGTAATTTTTGTACATTACAC-3'(SEQ ID NO:4972)
5'-AGUGGUAAUUUUUGUACAUUACAct-3'(SEQ ID NO:4730)
3'-GUUCACCAUUAAAAACAUGUAAUGUGA-5'(SEQ ID NO:4487)
KRAS-909靶:5'-CAAGTGGTAATTTTTGTACATTACACT-3'(SEQ ID NO:4973)
5'-UUGUACAUUACACUAAAUUAUUAgc-3'(SEQ ID NO:4731)
3'-AAAACAUGUAAUGUGAUUUAAUAAUCG-5'(SEQ ID NO:4488)
KRAS-920靶:5'-TTTTGTACATTACACTAAATTATTAGC-3'(SEQ ID NO:4974)
5'-UGUACAUUACACUAAAUUAUUAGca-3'(SEQ ID NO:4732)
3'-AAACAUGUAAUGUGAUUUAAUAAUCGU-5'(SEQ ID NO:4489)
KRAS-921靶:5'-TTTGTACATTACACTAAATTATTAGCA-3'(SEQ ID NO:4975)
5'-GUACAUUACACUAAAUUAUUAGCat-3'(SEQ ID NO:4733)
3'-AACAUGUAAUGUGAUUUAAUAAUCGUA-5'(SEQ ID NO:4490)
KRAS-922靶:5'-TTGTACATTACACTAAATTATTAGCAT-3'(SEQ ID NO:4976)
5'-UACAUUACACUAAAUUAUUAGCAtt-3'(SEQ ID NO:4734)
3'-ACAUGUAAUGUGAUUUAAUAAUCGUAA-5'(SEQ ID NO:4491)
KRAS-923靶:5'-TGTACATTACACTAAATTATTAGCATT-3'(SEQ ID NO:4977)
5'-ACAUUACACUAAAUUAUUAGCAUtt-3'(SEQ ID NO:4735)
3'-CAUGUAAUGUGAUUUAAUAAUCGUAAA-5'(SEQ ID NO:4492)
KRAS-924靶:5'-GTACATTACACTAAATTATTAGCATTT-3'(SEQ ID NO:4978)
5'-CAUUACACUAAAUUAUUAGCAUUtg-3'(SEQ ID NO:4736)
3'-AUGUAAUGUGAUUUAAUAAUCGUAAAC-5'(SEQ ID NO:4493)
KRAS-925靶:5'-TACATTACACTAAATTATTAGCATTTG-3'(SEQ ID NO:4979)
5'-AUUACACUAAAUUAUUAGCAUUUgt-3'(SEQ ID NO:4737)
3'-UGUAAUGUGAUUUAAUAAUCGUAAACA-5'(SEQ ID NO:4494)
KRAS-926靶:5'-ACATTACACTAAATTATTAGCATTTGT-3'(SEQ ID NO:4980)
5'-UUACACUAAAUUAUUAGCAUUUGtt-3'(SEQ ID NO:4738)
3'-GUAAUGUGAUUUAAUAAUCGUAAACAA-5'(SEQ ID NO:4495)
KRAS-927靶:5'-CATTACACTAAATTATTAGCATTTGTT-3'(SEQ ID NO:4981)
5'-UACACUAAAUUAUUAGCAUUUGUtt-3'(SEQ ID NO:4739)
3'-UAAUGUGAUUUAAUAAUCGUAAACAAA-5'(SEQ ID NO:4496)
KRAS-928靶:5'-ATTACACTAAATTATTAGCATTTGTTT-3'(SEQ ID NO:4982)
5'-UAUUAGCAUUUGUUUUAGCAUUAcc-3'(SEQ ID NO:4740)
3'-UAAUAAUCGUAAACAAAAUCGUAAUGG-5'(SEQ ID NO:4497)
KRAS-938靶:5'-ATTATTAGCATTTGTTTTAGCATTACC-3'(SEQ ID NO:4983)
5'-AUUAGCAUUUGUUUUAGCAUUACct-3'(SEQ ID NO:4741)
3'-AAUAAUCGUAAACAAAAUCGUAAUGGA-5'(SEQ ID NO:4498)
KRAS-939靶:5'-TTATTAGCATTTGTTTTAGCATTACCT-3'(SEQ ID NO:4984)
5'-UUAGCAUUUGUUUUAGCAUUACCta-3'(SEQ ID NO:4742)
3'-AUAAUCGUAAACAAAAUCGUAAUGGAU-5'(SEQ ID NO:4499)
KRAS-940靶:5'-TATTAGCATTTGTTTTAGCATTACCTA-3'(SEQ ID NO:4985)
5'-UAGCAUUUGUUUUAGCAUUACCUaa-3'(SEQ ID NO:4743)
3'-UAAUCGUAAACAAAAUCGUAAUGGAUU-5'(SEQ ID NO:4500)
KRAS-941靶:5'-ATTAGCATTTGTTTTAGCATTACCTAA-3'(SEQ ID NO:4986)
5'-AGCAUUUGUUUUAGCAUUACCUAat-3'(SEQ ID NO:4744)
3'-AAUCGUAAACAAAAUCGUAAUGGAUUA-5'(SEQ ID NO:4501)
KRAS-942靶:5'-TTAGCATTTGTTTTAGCATTACCTAAT-3'(SEQ ID NO:4987)
5'-GCAUUUGUUUUAGCAUUACCUAAtt-3'(SEQ ID NO:4745)
3'-AUCGUAAACAAAAUCGUAAUGGAUUAA-5'(SEQ ID NO:4502)
KRAS-943靶:5'-TAGCATTTGTTTTAGCATTACCTAATT-3'(SEQ ID NO:4988)
5'-CAUUUGUUUUAGCAUUACCUAAUtt-3'(SEQ ID NO:4746)
3'-UCGUAAACAAAAUCGUAAUGGAUUAAA-5'(SEQ ID NO:4503)
KRAS-944靶:5'-AGCATTTGTTTTAGCATTACCTAATTT-3'(SEQ ID NO:4989)
5'-AUUUGUUUUAGCAUUACCUAAUUtt-3'(SEQ ID NO:4747)
3'-CGUAAACAAAAUCGUAAUGGAUUAAAA-5'(SEQ ID NO:4504)
KRAS-945靶:5'-GCATTTGTTTTAGCATTACCTAATTTT-3'(SEQ ID NO:4990)
5'-UUUGUUUUAGCAUUACCUAAUUUtt-3'(SEQ ID NO:4748)
3'-GUAAACAAAAUCGUAAUGGAUUAAAAA-5'(SEQ ID NO:4505)
KRAS-946靶:5'-CATTTGTTTTAGCATTACCTAATTTTT-3'(SEQ ID NO:4991)
5'-CUUAUUUUAAAAUGACAGUGGAAgt-3'(SEQ ID NO:4749)
3'-ACGAAUAAAAUUUUACUGUCACCUUCA-5'(SEQ ID NO:4506)
KRAS-1010靶:5'-TGCTTATTTTAAAATGACAGTGGAAGT-3'(SEQ ID NO:4992)
5'-UAUUUUAAAAUGACAGUGGAAGUtt-3'(SEQ ID NO:4750)
3'-GAAUAAAAUUUUACUGUCACCUUCAAA-5'(SEQ ID NO:4507)
KRAS-1012靶:5'-CTTATTTTAAAATGACAGTGGAAGTTT-3'(SEQ ID NO:4993)
5'-UCUAAGUGCCAGUAUUCCCAGAGtt-3'(SEQ ID NO:4751)
3'-GGAGAUUCACGGUCAUAAGGGUCUCAA-5'(SEQ ID NO:4508)
KRAS-1045靶:5'-CCTCTAAGTGCCAGTATTCCCAGAGTT-3'(SEQ ID NO:4994)
5'-CAAAUUAAUGAAGCUUUUGAAUCat-3'(SEQ ID NO:4752)
3'-UUGUUUAAUUACUUCGAAAACUUAGUA-5'(SEQ ID NO:4509)
KRAS-1197靶:5'-AACAAATTAATGAAGCTTTTGAATCAT-3'(SEQ ID NO:4995)
5'-AAAUUAAUGAAGCUUUUGAAUCAtc-3'(SEQ ID NO:4753)
3'-UGUUUAAUUACUUCGAAAACUUAGUAG-5'(SEQ ID NO:4510)
KRAS-1198靶:5'-ACAAATTAATGAAGCTTTTGAATCATC-3'(SEQ ID NO:4996)
5'-UGUGUUUUAUCUAGUCACAUAAAtg-3'(SEQ ID NO:4754)
3'-AGACACAAAAUAGAUCAGUGUAUUUAC-5'(SEQ ID NO:4511)
KRAS-1230靶:5'-TCTGTGTTTTATCTAGTCACATAAATG-3'(SEQ ID NO:4997)
5'-GUGUUUUAUCUAGUCACAUAAAUgg-3'(SEQ ID NO:4755)
3'-GACACAAAAUAGAUCAGUGUAUUUACC-5'(SEQ ID NO:4512)
KRAS-1231靶:5'-CTGTGTTTTATCTAGTCACATAAATGG-3'(SEQ ID NO:4998)
5'-UUUUAUCUAGUCACAUAAAUGGAtt-3'(SEQ ID NO:4756)
3'-ACAAAAUAGAUCAGUGUAUUUACCUAA-5'(SEQ ID NO:4513)
KRAS-1234靶:5'-TGTTTTATCTAGTCACATAAATGGATT-3'(SEQ ID NO:4999)
5'-UAAAUGGAUUAAUUACUAAUUUCag-3'(SEQ ID NO:4757)
3'-GUAUUUACCUAAUUAAUGAUUAAAGUC-5'(SEQ ID NO:4514)
KRAS-1249靶:5'-CATAAATGGATTAATTACTAATTTCAG-3'(SEQ ID NO:5000)
5'-AAAUGGAUUAAUUACUAAUUUCAgt-3'(SEQ ID NO:4758)
3'-UAUUUACCUAAUUAAUGAUUAAAGUCA-5'(SEQ ID NO:4515)
KRAS-1250靶:5'-ATAAATGGATTAATTACTAATTTCAGT-3'(SEQ ID NO:5001)
5'-AUUGGUUUUUACUGAAACAUUGAgg-3'(SEQ ID NO:4759)
3'-AUUAACCAAAAAUGACUUUGUAACUCC-5'(SEQ ID NO:4516)
KRAS-1287靶:5'-TAATTGGTTTTTACTGAAACATTGAGG-3'(SEQ ID NO:5002)
5'-CAUUUCCUUUUCACAUUAGAUAAat-3'(SEQ ID NO:4760)
3'-CGGUAAAGGAAAAGUGUAAUCUAUUUA-5'(SEQ ID NO:4517)
KRAS-1527靶:5'-GCCATTTCCTTTTCACATTAGATAAAT-3'(SEQ ID NO:5003)
5'-CUUUUCACAUUAGAUAAAUUACUat-3'(SEQ ID NO:4761)
3'-AGGAAAAGUGUAAUCUAUUUAAUGAUA-5'(SEQ ID NO:4518)
KRAS-1533靶:5'-TCCTTTTCACATTAGATAAATTACTAT-3'(SEQ ID NO:5004)
5'-CAUUAGAUAAAUUACUAUAAAGAct-3'(SEQ ID NO:4762)
3'-GUGUAAUCUAUUUAAUGAUAUUUCUGA-5'(SEQ ID NO:4519)
KRAS-1540靶:5'-CACATTAGATAAATTACTATAAAGACT-3'(SEQ ID NO:5005)
5'-AUUAGAUAAAUUACUAUAAAGACtc-3'(SEQ ID NO:4763)
3'-UGUAAUCUAUUUAAUGAUAUUUCUGAG-5'(SEQ ID NO:4520)
KRAS-1541靶:5'-ACATTAGATAAATTACTATAAAGACTC-3'(SEQ ID NO:5006)
5'-UUAGAUAAAUUACUAUAAAGACUcc-3'(SEQ ID NO:4764)
3'-GUAAUCUAUUUAAUGAUAUUUCUGAGG-5'(SEQ ID NO:4521)
KRAS-1542靶:5'-CATTAGATAAATTACTATAAAGACTCC-3'(SEQ ID NO:5007)
5'-UAAGGCAGACCCAGUAUGAAAUGgg-3'(SEQ ID NO:4765)
3'-CAAUUCCGUCUGGGUCAUACUUUACCC-5'(SEQ ID NO:4522)
KRAS-1583靶:5'-GTTAAGGCAGACCCAGTATGAAATGGG-3'(SEQ ID NO:5008)
5'-AAGGCAGACCCAGUAUGAAAUGGgg-3'(SEQ ID NO:4766)
3'-AAUUCCGUCUGGGUCAUACUUUACCCC-5'(SEQ ID NO:4523)
KRAS-1584靶:5'-TTAAGGCAGACCCAGTATGAAATGGGG-3'(SEQ ID NO:5009)
5'-AGGCAGACCCAGUAUGAAAUGGGga-3'(SEQ ID NO:4767)
3'-AUUCCGUCUGGGUCAUACUUUACCCCU-5'(SEQ ID NO:4524)
KRAS-1585靶:5'-TAAGGCAGACCCAGTATGAAATGGGGA-3'(SEQ ID NO:5010)
5'-GGCAGACCCAGUAUGAAAUGGGGat-3'(SEQ ID NO:4768)
3'-UUCCGUCUGGGUCAUACUUUACCCCUA-5'(SEQ ID NO:4525)
KRAS-1586靶:5'-AAGGCAGACCCAGTATGAAATGGGGAT-3'(SEQ ID NO:5011)
5'-UAUGAAAUGGGGAUUAUUAUAGCaa-3'(SEQ ID NO:4769)
3'-UCAUACUUUACCCCUAAUAAUAUCGUU-5'(SEQ ID NO:4526)
KRAS-1597靶:5'-AGTATGAAATGGGGATTATTATAGCAA-3'(SEQ ID NO:5012)
5'-GGGAUUAUUAUAGCAACCAUUUUgg-3'(SEQ ID NO:4770)
3'-ACCCCUAAUAAUAUCGUUGGUAAAACC-5'(SEQ ID NO:4527)
KRAS-1606靶:5'-TGGGGATTATTATAGCAACCATTTTGG-3'(SEQ ID NO:5013)
5'-GGGCUAUAUUUACAUGCUACUAAat-3'(SEQ ID NO:4771)
3'-ACCCCGAUAUAAAUGUACGAUGAUUUA-5'(SEQ ID NO:4528)
KRAS-1630靶:5'-TGGGGCTATATTTACATGCTACTAAAT-3'(SEQ ID NO:5014)
5'-GGCUAUAUUUACAUGCUACUAAAtt-3'(SEQ ID NO:4772)
3'-CCCCGAUAUAAAUGUACGAUGAUUUAA-5'(SEQ ID NO:4529)
KRAS-1631靶:5'-GGGGCTATATTTACATGCTACTAAATT-3'(SEQ ID NO:5015)
5'-GCUAUAUUUACAUGCUACUAAAUtt-3'(SEQ ID NO:4773)
3'-CCCGAUAUAAAUGUACGAUGAUUUAAA-5'(SEQ ID NO:4530)
KRAS-1632靶:5'-GGGCTATATTTACATGCTACTAAATTT-3'(SEQ ID NO:5016)
5'-CUAUAUUUACAUGCUACUAAAUUtt-3'(SEQ ID NO:4774)
3'-CCGAUAUAAAUGUACGAUGAUUUAAAA-5'(SEQ ID NO:4531)
KRAS-1633靶:5'-GGCTATATTTACATGCTACTAAATTTT-3'(SEQ ID NO:5017)
5'-UAUAUUUACAUGCUACUAAAUUUtt-3'(SEQ ID NO:4775)
3'-CGAUAUAAAUGUACGAUGAUUUAAAAA-5'(SEQ ID NO:4532)
KRAS-1634靶:5'-GCTATATTTACATGCTACTAAATTTTT-3'(SEQ ID NO:5018)
5'-AUAUUUACAUGCUACUAAAUUUUta-3'(SEQ ID NO:4776)
3'-GAUAUAAAUGUACGAUGAUUUAAAAAU-5'(SEQ ID NO:4533)
KRAS-1635靶:5'-CTATATTTACATGCTACTAAATTTTTA-3'(SEQ ID NO:5019)
5'-UAUUUACAUGCUACUAAAUUUUUat-3'(SEQ ID NO:4777)
3'-AUAUAAAUGUACGAUGAUUUAAAAAUA-5'(SEQ ID NO:4534)
KRAS-1636靶:5'-TATATTTACATGCTACTAAATTTTTAT-3'(SEQ ID NO:5020)
5'-AUUUACAUGCUACUAAAUUUUUAta-3'(SEQ ID NO:4778)
3'-UAUAAAUGUACGAUGAUUUAAAAAUAU-5'(SEQ ID NO:4535)
KRAS-1637靶:5'-ATATTTACATGCTACTAAATTTTTATA-3'(SEQ ID NO:5021)
5'-UUUACAUGCUACUAAAUUUUUAUaa-3'(SEQ ID NO:4779)
3'-AUAAAUGUACGAUGAUUUAAAAAUAUU-5'(SEQ ID NO:4536)
KRAS-1638靶:5'-TATTTACATGCTACTAAATTTTTATAA-3'(SEQ ID NO:5022)
5'-UUACAUGCUACUAAAUUUUUAUAat-3'(SEQ ID NO:4780)
3'-UAAAUGUACGAUGAUUUAAAAAUAUUA-5'(SEQ ID NO:4537)
KRAS-1639靶:5'-ATTTACATGCTACTAAATTTTTATAAT-3'(SEQ ID NO:5023)
5'-UACAUGCUACUAAAUUUUUAUAAta-3'(SEQ ID NO:4781)
3'-AAAUGUACGAUGAUUUAAAAAUAUUAU-5'(SEQ ID NO:4538)
KRAS-1640靶:5'-TTTACATGCTACTAAATTTTTATAATA-3'(SEQ ID NO:5024)
5'-CUUUCAUAGUAUAACUUUAAAUCtt-3'(SEQ ID NO:4782)
3'-GAGAAAGUAUCAUAUUGAAAUUUAGAA-5'(SEQ ID NO:4539)
KRAS-1736靶:5'-CTCTTTCATAGTATAACTTTAAATCTT-3'(SEQ ID NO:5025)
5'-AUAGUAUAACUUUAAAUCUUUUCtt-3'(SEQ ID NO:4783)
3'-AGUAUCAUAUUGAAAUUUAGAAAAGAA-5'(SEQ ID NO:4540)
KRAS-1741靶:5'-TCATAGTATAACTTTAAATCTTTTCTT-3'(SEQ ID NO:5026)
5'-UAGUAUAACUUUAAAUCUUUUCUtc-3'(SEQ ID NO:4784)
3'-GUAUCAUAUUGAAAUUUAGAAAAGAAG-5'(SEQ ID NO:4541)
KRAS-1742靶:5'-CATAGTATAACTTTAAATCTTTTCTTC-3'(SEQ ID NO:5027)
5'-UAAAUCUUUUCUUCAACUUGAGUct-3'(SEQ ID NO:4785)
3'-AAAUUUAGAAAAGAAGUUGAACUCAGA-5'(SEQ ID NO:4542)
KRAS-1753靶:5'-TTTAAATCTTTTCTTCAACTTGAGTCT-3'(SEQ ID NO:5028)
5'-AAAUCUUUUCUUCAACUUGAGUCtt-3'(SEQ ID NO:4786)
3'-AAUUUAGAAAAGAAGUUGAACUCAGAA-5'(SEQ ID NO:4543)
KRAS-1754靶:5'-TTAAATCTTTTCTTCAACTTGAGTCTT-3'(SEQ ID NO:5029)
5'-CUUGAGUCUUUGAAGAUAGUUUUaa-3'(SEQ ID NO:4787)
3'-UUGAACUCAGAAACUUCUAUCAAAAUU-5'(SEQ ID NO:4544)
KRAS-1769靶:5'-AACTTGAGTCTTTGAAGATAGTTTTAA-3'(SEQ ID NO:5030)
5'-UGAGUCUUUGAAGAUAGUUUUAAtt-3'(SEQ ID NO:4788)
3'-GAACUCAGAAACUUCUAUCAAAAUUAA-5'(SEQ ID NO:4545)
KRAS-1771靶:5'-CTTGAGTCTTTGAAGATAGTTTTAATT-3'(SEQ ID NO:5031)
5'-GAGUCUUUGAAGAUAGUUUUAAUtc-3'(SEQ ID NO:4789)
3'-AACUCAGAAACUUCUAUCAAAAUUAAG-5'(SEQ ID NO:4546)
KRAS-1772靶:5'-TTGAGTCTTTGAAGATAGTTTTAATTC-3'(SEQ ID NO:5032)
5'-GAUAGUUUUAAUUCUGCUUGUGAca-3'(SEQ ID NO:4790)
3'-UUCUAUCAAAAUUAAGACGAACACUGU-5'(SEQ ID NO:4547)
KRAS-1783靶:5'-AAGATAGTTTTAATTCTGCTTGTGACA-3'(SEQ ID NO:5033)
5'-AUAGUUUUAAUUCUGCUUGUGACat-3'(SEQ ID NO:4791)
3'-UCUAUCAAAAUUAAGACGAACACUGUA-5'(SEQ ID NO:4548)
KRAS-1784靶:5'-AGATAGTTTTAATTCTGCTTGTGACAT-3'(SEQ ID NO:5034)
5'-UAGUUUUAAUUCUGCUUGUGACAtt-3'(SEQ ID NO:4792)
3'-CUAUCAAAAUUAAGACGAACACUGUAA-5'(SEQ ID NO:4549)
KRAS-1785靶:5'-GATAGTTTTAATTCTGCTTGTGACATT-3'(SEQ ID NO:5035)
5'-CUUGUGACAUUAAAAGAUUAUUUgg-3'(SEQ ID NO:4793)
3'-ACGAACACUGUAAUUUUCUAAUAAACC-5'(SEQ ID NO:4550)
KRAS-1799靶:5'-TGCTTGTGACATTAAAAGATTATTTGG-3'(SEQ ID NO:5036)
5'-UAUUAACUCAAAAGUUGAGAUUUtg-3'(SEQ ID NO:4794)
3'-UUAUAAUUGAGUUUUCAACUCUAAAAC-5'(SEQ ID NO:4551)
KRAS-2100靶:5'-AATATTAACTCAAAAGTTGAGATTTTG-3'(SEQ ID NO:5037)
5'-UGUGCCAAGACAUUAAUUUUUUUtt-3'(SEQ ID NO:4795)
3'-CCACACGGUUCUGUAAUUAAAAAAAAA-5'(SEQ ID NO:4552)
KRAS-2134靶:5'-GGTGTGCCAAGACATTAATTTTTTTTT-3'(SEQ ID NO:5038)
5'-UGGUUAAAUUAACAUUGCAUAAAca-3'(SEQ ID NO:4796)
3'-UGACCAAUUUAAUUGUAACGUAUUUGU-5'(SEQ ID NO:4553)
KRAS-2216靶:5'-ACTGGTTAAATTAACATTGCATAAACA-3'(SEQ ID NO:5039)
5'-GGUUAAAUUAACAUUGCAUAAACac-3'(SEQ ID NO:4797)
3'-GACCAAUUUAAUUGUAACGUAUUUGUG-5'(SEQ ID NO:4554)
KRAS-2217靶:5'-CTGGTTAAATTAACATTGCATAAACAC-3'(SEQ ID NO:5040)
5'-GUUAAAUUAACAUUGCAUAAACAct-3'(SEQ ID NO:4798)
3'-ACCAAUUUAAUUGUAACGUAUUUGUGA-5'(SEQ ID NO:4555)
KRAS-2218靶:5'-TGGTTAAATTAACATTGCATAAACACT-3'(SEQ ID NO:5041)
5'-AUUGCAUAAACACUUUUCAAGUCtg-3'(SEQ ID NO:4799)
3'-UGUAACGUAUUUGUGAAAAGUUCAGAC-5'(SEQ ID NO:4556)
KRAS-2229靶:5'-ACATTGCATAAACACTTTTCAAGTCTG-3'(SEQ ID NO:5042)
5'-AAGUCUGAUCCAUAUUUAAUAAUgc-3'(SEQ ID NO:4800)
3'-AGUUCAGACUAGGUAUAAAUUAUUACG-5'(SEQ ID NO:4557)
KRAS-2247靶:5'-TCAAGTCTGATCCATATTTAATAATGC-3'(SEQ ID NO:5043)
5'-UAAAAUAAAUGAAGUGAGAUGGCat-3'(SEQ ID NO:4801)
3'-AAAUUUUAUUUACUUCACUCUACCGUA-5'(SEQ ID NO:4558)
KRAS-2326靶:5'-TTTAAAATAAATGAAGTGAGATGGCAT-3'(SEQ ID NO:5044)
5'-AAAAUAAAUGAAGUGAGAUGGCAtg-3'(SEQ ID NO:4802)
3'-AAUUUUAUUUACUUCACUCUACCGUAC-5'(SEQ ID NO:4559)
KRAS-2327靶:5'-TTAAAATAAATGAAGTGAGATGGCATG-3'(SEQ ID NO:5045)
5'-AAGCUCAGCACAAUCUGUAAAUUtt-3'(SEQ ID NO:4803)
3'-AGUUCGAGUCGUGUUAGACAUUUAAAA-5'(SEQ ID NO:4560)
KRAS-2547靶:5'-TCAAGCTCAGCACAATCTGTAAATTTT-3'(SEQ ID NO:5046)
5'-AGCUCAGCACAAUCUGUAAAUUUtt-3'(SEQ ID NO:4804)
3'-GUUCGAGUCGUGUUAGACAUUUAAAAA-5'(SEQ ID NO:4561)
KRAS-2548靶:5'-CAAGCTCAGCACAATCTGTAAATTTTT-3'(SEQ ID NO:5047)
5'-AUAACUGUGAUUCUUUUAGGACAat-3'(SEQ ID NO:4805)
3'-CGUAUUGACACUAAGAAAAUCCUGUUA-5'(SEQ ID NO:4562)
KRAS-3741靶:5'-GCATAACTGTGATTCTTTTAGGACAAT-3'(SEQ ID NO:5048)
5'-UGUGAUUCUUUUAGGACAAUUACtg-3'(SEQ ID NO:4806)
3'-UGACACUAAGAAAAUCCUGUUAAUGAC-5'(SEQ ID NO:4563)
KRAS-3746靶:5'-ACTGTGATTCTTTTAGGACAATTACTG-3'(SEQ ID NO:5049)
5'-GUGAUUCUUUUAGGACAAUUACUgt-3'(SEQ ID NO:4807)
3'-GACACUAAGAAAAUCCUGUUAAUGACA-5'(SEQ ID NO:4564)
KRAS-3747靶:5'-CTGTGATTCTTTTAGGACAATTACTGT-3'(SEQ ID NO:5050)
5'-UGUAUGUCAGAUAUUCAUAUUGAcc-3'(SEQ ID NO:4808)
3'-CCACAUACAGUCUAUAAGUAUAACUGG-5'(SEQ ID NO:4565)
KRAS-3783靶:5'-GGTGTATGTCAGATATTCATATTGACC-3'(SEQ ID NO:5051)
5'-GUAUGUCAGAUAUUCAUAUUGACcc-3'(SEQ ID NO:4809)
3'-CACAUACAGUCUAUAAGUAUAACUGGG-5'(SEQ ID NO:4566)
KRAS-3784靶:5'-GTGTATGTCAGATATTCATATTGACCC-3'(SEQ ID NO:5052)
5'-AAUGUGUAAUAUUCCAGUUUUCUct-3'(SEQ ID NO:4810)
3'-GUUUACACAUUAUAAGGUCAAAAGAGA-5'(SEQ ID NO:4567)
KRAS-3810靶:5'-CAAATGTGTAATATTCCAGTTTTCTCT-3'(SEQ ID NO:5053)
5'-CACUGCAUAGGAAUUUAGAACCUaa-3'(SEQ ID NO:4811)
3'-GUGUGACGUAUCCUUAAAUCUUGGAUU-5'(SEQ ID NO:4568)
KRAS-4396靶:5'-CACACTGCATAGGAATTTAGAACCTAA-3'(SEQ ID NO:5054)
5'-CACCAUUGCACAAUUUUGUCCUAat-3'(SEQ ID NO:4812)
3'-CAGUGGUAACGUGUUAAAACAGGAUUA-5'(SEQ ID NO:4569)
KRAS-4447靶:5'-GTCACCATTGCACAATTTTGTCCTAAT-3'(SEQ ID NO:5055)
5'-ACCAUUGCACAAUUUUGUCCUAAta-3'(SEQ ID NO:4813)
3'-AGUGGUAACGUGUUAAAACAGGAUUAU-5'(SEQ ID NO:4570)
KRAS-4448靶:5'-TCACCATTGCACAATTTTGTCCTAATA-3'(SEQ ID NO:5056)
5'-CCAUUGCACAAUUUUGUCCUAAUat-3'(SEQ ID NO:4814)
3'-GUGGUAACGUGUUAAAACAGGAUUAUA-5'(SEQ ID NO:4571)
KRAS-4449靶:5'-CACCATTGCACAATTTTGTCCTAATAT-3'(SEQ ID NO:5057)
5'-CAUUGCACAAUUUUGUCCUAAUAta-3'(SEQ ID NO:4815)
3'-UGGUAACGUGUUAAAACAGGAUUAUAU-5'(SEQ ID NO:4572)
KRAS-4450靶:5'-ACCATTGCACAATTTTGTCCTAATATA-3'(SEQ ID NO:5058)
5'-AUUGCACAAUUUUGUCCUAAUAUat-3'(SEQ ID NO:4816)
3'-GGUAACGUGUUAAAACAGGAUUAUAUA-5'(SEQ ID NO:4573)
KRAS-4451靶:5'-CCATTGCACAATTTTGTCCTAATATAT-3'(SEQ ID NO:5059)
5'-UUGCACAAUUUUGUCCUAAUAUAta-3'(SEQ ID NO:4817)
3'-GUAACGUGUUAAAACAGGAUUAUAUAU-5'(SEQ ID NO:4574)
KRAS-4452靶:5'-CATTGCACAATTTTGTCCTAATATATA-3'(SEQ ID NO:5060)
5'-UAGCAUGAAUUCUGCAUUGAGAAac-3'(SEQ ID NO:4818)
3'-CUAUCGUACUUAAGACGUAACUCUUUG-5'(SEQ ID NO:4575)
KRAS-4748靶:5'-GATAGCATGAATTCTGCATTGAGAAAC-3'(SEQ ID NO:5061)
5'-AGCAUGAAUUCUGCAUUGAGAAAct-3'(SEQ ID NO:4819)
3'-UAUCGUACUUAAGACGUAACUCUUUGA-5'(SEQ ID NO:4576)
KRAS-4749靶:5'-ATAGCATGAATTCTGCATTGAGAAACT-3'(SEQ ID NO:5062)
5'-UUUGAAGUGCCUGUUUGGGAUAAtg-3'(SEQ ID NO:4820)
3'-UCAAACUUCACGGACAAACCCUAUUAC-5'(SEQ ID NO:4577)
KRAS-4878靶:5'-AGTTTGAAGTGCCTGTTTGGGATAATG-3'(SEQ ID NO:5063)
5'-UUGAAGUGCCUGUUUGGGAUAAUga-3'(SEQ ID NO:4821)
3'-CAAACUUCACGGACAAACCCUAUUACU-5'(SEQ ID NO:4578)
KRAS-4879靶:5'-GTTTGAAGTGCCTGTTTGGGATAATGA-3'(SEQ ID NO:5064)
5'-UGAAGUGCCUGUUUGGGAUAAUGat-3'(SEQ ID NO:4822)
3'-AAACUUCACGGACAAACCCUAUUACUA-5'(SEQ ID NO:4579)
KRAS-4880靶:5'-TTTGAAGTGCCTGTTTGGGATAATGAT-3'(SEQ ID NO:5065)
5'-UUUGAGUGCCAAUUUCUUACUAGta-3'(SEQ ID NO:4823)
3'-GGAAACUCACGGUUAAAGAAUGAUCAU-5'(SEQ ID NO:4580)
KRAS-5073靶:5'-CCTTTGAGTGCCAATTTCTTACTAGTA-3'(SEQ ID NO:5066)
5'-UUGAGUGCCAAUUUCUUACUAGUac-3'(SEQ ID NO:4824)
3'-GAAACUCACGGUUAAAGAAUGAUCAUG-5'(SEQ ID NO:4581)
KRAS-5074靶:5'-CTTTGAGTGCCAATTTCTTACTAGTAC-3'(SEQ ID NO:5067)
5'-UGAGUGCCAAUUUCUUACUAGUAct-3'(SEQ ID NO:4825)
3'-AAACUCACGGUUAAAGAAUGAUCAUGA-5'(SEQ ID NO:4582)
KRAS-5075靶:5'-TTTGAGTGCCAATTTCTTACTAGTACT-3'(SEQ ID NO:5068)
5'-GAGUGCCAAUUUCUUACUAGUACta-3'(SEQ ID NO:4826)
3'-AACUCACGGUUAAAGAAUGAUCAUGAU-5'(SEQ ID NO:4583)
KRAS-5076靶:5'-TTGAGTGCCAATTTCTTACTAGTACTA-3'(SEQ ID NO:5069)
5'-AGUGCCAAUUUCUUACUAGUACUat-3'(SEQ ID NO:4827)
3'-ACUCACGGUUAAAGAAUGAUCAUGAUA-5'(SEQ ID NO:4584)
KRAS-5077靶:5'-TGAGTGCCAATTTCTTACTAGTACTAT-3'(SEQ ID NO:5070)
5'-GUGCCAAUUUCUUACUAGUACUAtt-3'(SEQ ID NO:4828)
3'-CUCACGGUUAAAGAAUGAUCAUGAUAA-5'(SEQ ID NO:4585)
KRAS-5078靶:5'-GAGTGCCAATTTCTTACTAGTACTATT-3'(SEQ ID NO:5071)
5'-AUGUAUUUUAACUAUUUUUGUAUag-3'(SEQ ID NO:4829)
3'-CUUACAUAAAAUUGAUAAAAACAUAUC-5'(SEQ ID NO:4586)
KRAS-5128靶:5'-GAATGTATTTTAACTATTTTTGTATAG-3'(SEQ ID NO:5072)
5'-UGUAUUUUAACUAUUUUUGUAUAgt-3'(SEQ ID NO:4830)
3'-UUACAUAAAAUUGAUAAAAACAUAUCA-5'(SEQ ID NO:4587)
KRAS-5129靶:5'-AATGTATTTTAACTATTTTTGTATAGT-3'(SEQ ID NO:5073)
5'-ACUAUUUUUGUAUAGUGUAAACUga-3'(SEQ ID NO:4831)
3'-AUUGAUAAAAACAUAUCACAUUUGACU-5'(SEQ ID NO:4588)
KRAS-5138靶:5'-TAACTATTTTTGTATAGTGTAAACTGA-3'(SEQ ID NO:5074)
5'-CUAUUUUUGUAUAGUGUAAACUGaa-3'(SEQ ID NO:4832)
3'-UUGAUAAAAACAUAUCACAUUUGACUU-5'(SEQ ID NO:4589)
KRAS-5139靶:5'-AACTATTTTTGTATAGTGTAAACTGAA-3'(SEQ ID NO:5075)
5'-UAUUUUUGUAUAGUGUAAACUGAaa-3'(SEQ ID NO:4833)
3'-UGAUAAAAACAUAUCACAUUUGACUUU-5'(SEQ ID NO:4590)
KRAS-5140靶:5'-ACTATTTTTGTATAGTGTAAACTGAAA-3'(SEQ ID NO:5076)
5'-AUUUUUGUAUAGUGUAAACUGAAac-3'(SEQ ID NO:4834)
3'-GAUAAAAACAUAUCACAUUUGACUUUG-5'(SEQ ID NO:4591)
KRAS-5141靶:5'-CTATTTTTGTATAGTGTAAACTGAAAC-3'(SEQ ID NO:5077)
5'-UUUUUGUAUAGUGUAAACUGAAAca-3'(SEQ ID NO:4835)
3'-AUAAAAACAUAUCACAUUUGACUUUGU-5'(SEQ ID NO:4592)
KRAS-5142靶:5'-TATTTTTGTATAGTGTAAACTGAAACA-3'(SEQ ID NO:5078)
5'-UUUUGUAUAGUGUAAACUGAAACat-3'(SEQ ID NO:4836)
3'-UAAAAACAUAUCACAUUUGACUUUGUA-5'(SEQ ID NO:4593)
KRAS-5143靶:5'-ATTTTTGTATAGTGTAAACTGAAACAT-3'(SEQ ID NO:5079)
5'-AACAUGCACAUUUUGUACAUUGUgc-3'(SEQ ID NO:4837)
3'-CUUUGUACGUGUAAAACAUGUAACACG-5'(SEQ ID NO:4594)
KRAS-5163靶:5'-GAAACATGCACATTTTGTACATTGTGC-3'(SEQ ID NO:5080)
5'-ACAUGCACAUUUUGUACAUUGUGct-3'(SEQ ID NO:4838)
3'-UUUGUACGUGUAAAACAUGUAACACGA-5'(SEQ ID NO:4595)
KRAS-5164靶:5'-AAACATGCACATTTTGTACATTGTGCT-3'(SEQ ID NO:5081)
5'-UGCACAUUUUGUACAUUGUGCUUtc-3'(SEQ ID NO:4839)
3'-GUACGUGUAAAACAUGUAACACGAAAG-5'(SEQ ID NO:4596)
KRAS-5167靶:5'-CATGCACATTTTGTACATTGTGCTTTC-3'(SEQ ID NO:5082)
5'-GCACAUUUUGUACAUUGUGCUUUct-3'(SEQ ID NO:4840)
3'-UACGUGUAAAACAUGUAACACGAAAGA-5'(SEQ ID NO:4597)
KRAS-5168靶:5'-ATGCACATTTTGTACATTGTGCTTTCT-3'(SEQ ID NO:5083)
5'-CACAUUUUGUACAUUGUGCUUUCtt-3'(SEQ ID NO:4841)
3'-ACGUGUAAAACAUGUAACACGAAAGAA-5'(SEQ ID NO:4598)
KRAS-5169靶:5'-TGCACATTTTGTACATTGTGCTTTCTT-3'(SEQ ID NO:5084)
5'-ACAUUUUGUACAUUGUGCUUUCUtt-3'(SEQ ID NO:4842)
3'-CGUGUAAAACAUGUAACACGAAAGAAA-5'(SEQ ID NO:4599)
KRAS-5170靶:5'-GCACATTTTGTACATTGTGCTTTCTTT-3'(SEQ ID NO:5085)
5'-CAUUUUGUACAUUGUGCUUUCUUtt-3'(SEQ ID NO:4843)
3'-GUGUAAAACAUGUAACACGAAAGAAAA-5'(SEQ ID NO:4600)
KRAS-5171靶:5'-CACATTTTGTACATTGTGCTTTCTTTT-3'(SEQ ID NO:5086)
5'-AUUUUGUACAUUGUGCUUUCUUUtg-3'(SEQ ID NO:4844)
3'-UGUAAAACAUGUAACACGAAAGAAAAC-5'(SEQ ID NO:4601)
KRAS-5172靶:5'-ACATTTTGTACATTGTGCTTTCTTTTG-3'(SEQ ID NO:5087)
5'-UUUUGUACAUUGUGCUUUCUUUUgt-3'(SEQ ID NO:4845)
3'-GUAAAACAUGUAACACGAAAGAAAACA-5'(SEQ ID NO:4602)
KRAS-5173靶:5'-CATTTTGTACATTGTGCTTTCTTTTGT-3'(SEQ ID NO:5088)
5'-UGGGACAUAUGCAGUGUGAUCCAgt-3'(SEQ ID NO:4846)
3'-ACACCCUGUAUACGUCACACUAGGUCA-5'(SEQ ID NO:4603)
KRAS-5197靶:5'-TGTGGGACATATGCAGTGTGATCCAGT-3'(SEQ ID NO:5089)
5'-GGGACAUAUGCAGUGUGAUCCAGtt-3'(SEQ ID NO:4847)
3'-CACCCUGUAUACGUCACACUAGGUCAA-5'(SEQ ID NO:4604)
KRAS-5198靶:5'-GTGGGACATATGCAGTGTGATCCAGTT-3'(SEQ ID NO:5090)
5'-GGACAUAUGCAGUGUGAUCCAGUtg-3'(SEQ ID NO:4848)
3'-ACCCUGUAUACGUCACACUAGGUCAAC-5'(SEQ ID NO:4605)
KRAS-5199靶:5'-TGGGACATATGCAGTGTGATCCAGTTG-3'(SEQ ID NO:5091)
5'-GACAUAUGCAGUGUGAUCCAGUUgt-3'(SEQ ID NO:4849)
3'-CCCUGUAUACGUCACACUAGGUCAACA-5'(SEQ ID NO:4606)
KRAS-5200靶:5'-GGGACATATGCAGTGTGATCCAGTTGT-3'(SEQ ID NO:5092)
5'-ACAUAUGCAGUGUGAUCCAGUUGtt-3'(SEQ ID NO:4850)
3'-CCUGUAUACGUCACACUAGGUCAACAA-5'(SEQ ID NO:4607)
KRAS-5201靶:5'-GGACATATGCAGTGTGATCCAGTTGTT-3'(SEQ ID NO:5093)
5'-CAUAUGCAGUGUGAUCCAGUUGUtt-3'(SEQ ID NO:4851)
3'-CUGUAUACGUCACACUAGGUCAACAAA-5'(SEQ ID NO:4608)
KRAS-5202靶:5'-GACATATGCAGTGTGATCCAGTTGTTT-3'(SEQ ID NO:5094)
5'-AUAUGCAGUGUGAUCCAGUUGUUtt-3'(SEQ ID NO:4852)
3'-UGUAUACGUCACACUAGGUCAACAAAA-5'(SEQ ID NO:4609)
KRAS-5203靶:5'-ACATATGCAGTGTGATCCAGTTGTTTT-3'(SEQ ID NO:5095)
5'-UAUGCAGUGUGAUCCAGUUGUUUtc-3'(SEQ ID NO:4853)
3'-GUAUACGUCACACUAGGUCAACAAAAG-5'(SEQ ID NO:4610)
KRAS-5204靶:5'-CATATGCAGTGTGATCCAGTTGTTTTC-3'(SEQ ID NO:5096)
5'-AUGCAGUGUGAUCCAGUUGUUUUcc-3'(SEQ ID NO:4854)
3'-UAUACGUCACACUAGGUCAACAAAAGG-5'(SEQ ID NO:4611)
KRAS-5205靶:5'-ATATGCAGTGTGATCCAGTTGTTTTCC-3'(SEQ ID NO:5097)
5'-AGUGUGAUCCAGUUGUUUUCCAUca-3'(SEQ ID NO:4855)
3'-CGUCACACUAGGUCAACAAAAGGUAGU-5'(SEQ ID NO:4612)
KRAS-5209靶:5'-GCAGTGTGATCCAGTTGTTTTCCATCA-3'(SEQ ID NO:5098)
5'-GUGUGAUCCAGUUGUUUUCCAUCat-3'(SEQ ID NO:4856)
3'-GUCACACUAGGUCAACAAAAGGUAGUA-5'(SEQ ID NO:4613)
KRAS-5210靶:5'-CAGTGTGATCCAGTTGTTTTCCATCAT-3'(SEQ ID NO:5099)
5'-UGUGAUCCAGUUGUUUUCCAUCAtt-3'(SEQ ID NO:4857)
3'-UCACACUAGGUCAACAAAAGGUAGUAA-5'(SEQ ID NO:4614)
KRAS-5211靶:5'-AGTGTGATCCAGTTGTTTTCCATCATT-3'(SEQ ID NO:5100)
5'-GUGAUCCAGUUGUUUUCCAUCAUtt-3'(SEQ ID NO:4858)
3'-CACACUAGGUCAACAAAAGGUAGUAAA-5'(SEQ ID NO:4615)
KRAS-5212靶:5'-GTGTGATCCAGTTGTTTTCCATCATTT-3'(SEQ ID NO:5101)
5'-UGAUCCAGUUGUUUUCCAUCAUUtg-3'(SEQ ID NO:4859)
3'-ACACUAGGUCAACAAAAGGUAGUAAAC-5'(SEQ ID NO:4616)
KRAS-5213靶:5'-TGTGATCCAGTTGTTTTCCATCATTTG-3'(SEQ ID NO:5102)
5'-GAUCCAGUUGUUUUCCAUCAUUUgg-3'(SEQ ID NO:4860)
3'-CACUAGGUCAACAAAAGGUAGUAAACC-5'(SEQ ID NO:4617)
KRAS-5214靶:5'-GTGATCCAGTTGTTTTCCATCATTTGG-3'(SEQ ID NO:5103)
5'-UUUGGUUGCGCUGACCUAGGAAUgt-3'(SEQ ID NO:4861)
3'-GUAAACCAACGCGACUGGAUCCUUACA-5'(SEQ ID NO:4618)
KRAS-5234靶:5'-CATTTGGTTGCGCTGACCTAGGAATGT-3'(SEQ ID NO:5104)
5'-UUGGUUGCGCUGACCUAGGAAUGtt-3'(SEQ ID NO:4862)
3'-UAAACCAACGCGACUGGAUCCUUACAA-5'(SEQ ID NO:4619)
KRAS-5235靶:5'-ATTTGGTTGCGCTGACCTAGGAATGTT-3'(SEQ ID NO:5105)
5'-GGAAUGUUGGUCAUAUCAAACAUta-3'(SEQ ID NO:4863)
3'-AUCCUUACAACCAGUAUAGUUUGUAAU-5'(SEQ ID NO:4620)
KRAS-5252靶:5'-TAGGAATGTTGGTCATATCAAACATTA-3'(SEQ ID NO:5106)
5'-GAAUGUUGGUCAUAUCAAACAUUaa-3'(SEQ ID NO:4864)
3'-UCCUUACAACCAGUAUAGUUUGUAAUU-5'(SEQ ID NO:4621)
KRAS-5253靶:5'-AGGAATGTTGGTCATATCAAACATTAA-3'(SEQ ID NO:5107)
5'-AAUGUUGGUCAUAUCAAACAUUAaa-3'(SEQ ID NO:4865)
3'-CCUUACAACCAGUAUAGUUUGUAAUUU-5'(SEQ ID NO:4622)
KRAS-5254靶:5'-GGAATGTTGGTCATATCAAACATTAAA-3'(SEQ ID NO:5108)
5'-AUGUUGGUCAUAUCAAACAUUAAaa-3'(SEQ ID NO:4866)
3'-CUUACAACCAGUAUAGUUUGUAAUUUU-5'(SEQ ID NO:4623)
KRAS-5255靶:5'-GAATGTTGGTCATATCAAACATTAAAA-3'(SEQ ID NO:5109)
5'-UGUUGGUCAUAUCAAACAUUAAAaa-3'(SEQ ID NO:4867)
3'-UUACAACCAGUAUAGUUUGUAAUUUUU-5'(SEQ ID NO:4624)
KRAS-5256靶:5'-AATGTTGGTCATATCAAACATTAAAAA-3'(SEQ ID NO:5110)
5'-GUUGGUCAUAUCAAACAUUAAAAat-3'(SEQ ID NO:4868)
3'-UACAACCAGUAUAGUUUGUAAUUUUUA-5'(SEQ ID NO:4625)
KRAS-5257靶:5'-ATGTTGGTCATATCAAACATTAAAAAT-3'(SEQ ID NO:5111)
5'-UUGGUCAUAUCAAACAUUAAAAAtg-3'(SEQ ID NO:4869)
3'-ACAACCAGUAUAGUUUGUAAUUUUUAC-5'(SEQ ID NO:4626)
KRAS-5258靶:5'-TGTTGGTCATATCAAACATTAAAAATG-3'(SEQ ID NO:5112)
5'-UGGUCAUAUCAAACAUUAAAAAUga-3'(SEQ ID NO:4870)
3'-CAACCAGUAUAGUUUGUAAUUUUUACU-5'(SEQ ID NO:4627)
KRAS-5259靶:5'-GTTGGTCATATCAAACATTAAAAATGA-3'(SEQ ID NO:5113)
5'-GGUCAUAUCAAACAUUAAAAAUGac-3'(SEQ ID NO:4871)
3'-AACCAGUAUAGUUUGUAAUUUUUACUG-5'(SEQ ID NO:4628)
KRAS-5260靶:5'-TTGGTCATATCAAACATTAAAAATGAC-3'(SEQ ID NO:5114)
5'-AAAUUAACUUUUAAAUGUUUAUAgg-3'(SEQ ID NO:4872)
3'-ACUUUAAUUGAAAAUUUACAAAUAUCC-5'(SEQ ID NO:4629)
KRAS-5299靶:5'-TGAAATTAACTTTTAAATGTTTATAGG-3'(SEQ ID NO:5115)
5'-AAUUAACUUUUAAAUGUUUAUAGga-3'(SEQ ID NO:4873)
3'-CUUUAAUUGAAAAUUUACAAAUAUCCU-5'(SEQ ID NO:4630)
KRAS-5300靶:5'-GAAATTAACTTTTAAATGTTTATAGGA-3'(SEQ ID NO:5116)
5'-AACUUUUAAAUGUUUAUAGGAGUat-3'(SEQ ID NO:4874)
3'-AAUUGAAAAUUUACAAAUAUCCUCAUA-5'(SEQ ID NO:4631)
KRAS-5304靶:5'-TTAACTTTTAAATGTTTATAGGAGTAT-3'(SEQ ID NO:5117)
5'-ACUUUUAAAUGUUUAUAGGAGUAtg-3'(SEQ ID NO:4875)
3'-AUUGAAAAUUUACAAAUAUCCUCAUAC-5'(SEQ ID NO:4632)
KRAS-5305靶:5'-TAACTTTTAAATGTTTATAGGAGTATG-3'(SEQ ID NO:5118)
5'-CUUUUAAAUGUUUAUAGGAGUAUgt-3'(SEQ ID NO:4876)
3'-UUGAAAAUUUACAAAUAUCCUCAUACA-5'(SEQ ID NO:4633)
KRAS-5306靶:5'-AACTTTTAAATGTTTATAGGAGTATGT-3'(SEQ ID NO:5119)
5'-UUUUAAAUGUUUAUAGGAGUAUGtg-3'(SEQ ID NO:4877)
3'-UGAAAAUUUACAAAUAUCCUCAUACAC-5'(SEQ ID NO:4634)
KRAS-5307靶:5'-ACTTTTAAATGTTTATAGGAGTATGTG-3'(SEQ ID NO:5120)
5'-UUUAAAUGUUUAUAGGAGUAUGUgc-3'(SEQ ID NO:4878)
3'-GAAAAUUUACAAAUAUCCUCAUACACG-5'(SEQ ID NO:4635)
KRAS-5308靶:5'-CTTTTAAATGTTTATAGGAGTATGTGC-3'(SEQ ID NO:5121)
5'-UUAAAUGUUUAUAGGAGUAUGUGct-3'(SEQ ID NO:4879)
3'-AAAAUUUACAAAUAUCCUCAUACACGA-5'(SEQ ID NO:4636)
KRAS-5309靶:5'-TTTTAAATGTTTATAGGAGTATGTGCT-3'(SEQ ID NO:5122)
5'-AAAUUUGUAAUAUUUUUGUCAUGaa-3'(SEQ ID NO:4880)
3'-AUUUUAAACAUUAUAAAAACAGUACUU-5'(SEQ ID NO:4637)
KRAS-5347靶:5'-TAAAATTTGTAATATTTTTGTCATGAA-3'(SEQ ID NO:5123)
5'-AAUUUGUAAUAUUUUUGUCAUGAac-3'(SEQ ID NO:4881)
3'-UUUUAAACAUUAUAAAAACAGUACUUG-5'(SEQ ID NO:4638)
KRAS-5348靶:5'-AAAATTTGTAATATTTTTGTCATGAAC-3'(SEQ ID NO:5124)
5'-AUUUGUAAUAUUUUUGUCAUGAAct-3'(SEQ ID NO:4882)
3'-UUUAAACAUUAUAAAAACAGUACUUGA-5'(SEQ ID NO:4639)
KRAS-5349靶:5'-AAATTTGTAATATTTTTGTCATGAACT-3'(SEQ ID NO:5125)
5'-UUUGUAAUAUUUUUGUCAUGAACtg-3'(SEQ ID NO:4883)
3'-UUAAACAUUAUAAAAACAGUACUUGAC-5'(SEQ ID NO:4640)
KRAS-5350靶:5'-AATTTGTAATATTTTTGTCATGAACTG-3'(SEQ ID NO:5126)
5'-UUGUAAUAUUUUUGUCAUGAACUgt-3'(SEQ ID NO:4884)
3'-UAAACAUUAUAAAAACAGUACUUGACA-5'(SEQ ID NO:4641)
KRAS-5351靶:5'-ATTTGTAATATTTTTGTCATGAACTGT-3'(SEQ ID NO:5127)
5'-UGUAAUAUUUUUGUCAUGAACUGta-3'(SEQ ID NO:4885)
3'-AAACAUUAUAAAAACAGUACUUGACAU-5'(SEQ ID NO:4642)
KRAS-5352靶:5'-TTTGTAATATTTTTGTCATGAACTGTA-3'(SEQ ID NO:5128)
5'-GUAAUAUUUUUGUCAUGAACUGUac-3'(SEQ ID NO:4886)
3'-AACAUUAUAAAAACAGUACUUGACAUG-5'(SEQ ID NO:4643)
KRAS-5353靶:5'-TTGTAATATTTTTGTCATGAACTGTAC-3'(SEQ ID NO:5129)
5'-UAAUAUUUUUGUCAUGAACUGUAct-3'(SEQ ID NO:4887)
3'-ACAUUAUAAAAACAGUACUUGACAUGA-5'(SEQ ID NO:4644)
KRAS-5354靶:5'-TGTAATATTTTTGTCATGAACTGTACT-3'(SEQ ID NO:5130)
5'-AUUGUAAUGUAAUAAAAAUAGUUac-3'(SEQ ID NO:4888)
3'-AAUAACAUUACAUUAUUUUUAUCAAUG-5'(SEQ ID NO:4645)
KRAS-5389靶:5'-TTATTGTAATGTAATAAAAATAGTTAC-3'(SEQ ID NO:5131)
5'-UUGUAAUGUAAUAAAAAUAGUUAca-3'(SEQ ID NO:4889)
3'-AUAACAUUACAUUAUUUUUAUCAAUGU-5'(SEQ ID NO:4646)
KRAS-5390靶:5'-TATTGTAATGTAATAAAAATAGTTACA-3'(SEQ ID NO:5132)
5'-UGUAAUGUAAUAAAAAUAGUUACag-3'(SEQ ID NO:4890)
3'-UAACAUUACAUUAUUUUUAUCAAUGUC-5'(SEQ ID NO:4647)
KRAS-5391靶:5'-ATTGTAATGTAATAAAAATAGTTACAG-3'(SEQ ID NO:5133)
5'-GUAAUGUAAUAAAAAUAGUUACAgt-3'(SEQ ID NO:4891)
3'-AACAUUACAUUAUUUUUAUCAAUGUCA-5'(SEQ ID NO:4648)
KRAS-5392靶:5'-TTGTAATGTAATAAAAATAGTTACAGT-3'(SEQ ID NO:5134)
5'-UAAUGUAAUAAAAAUAGUUACAGtg-3'(SEQ ID NO:4892)
3'-ACAUUACAUUAUUUUUAUCAAUGUCAC-5'(SEQ ID NO:4649)
KRAS-5393靶:5'-TGTAATGTAATAAAAATAGTTACAGTG-3'(SEQ ID NO:5135)
与上表2-5中一样,上表8中带下划线的核苷酸残基表示2’-O-甲基修饰的残基;核糖核苷酸残基以大写字母显示,而脱氧核糖核苷酸残基以小写字母显示。
在人HeLa细胞和小鼠Hepa1-6细胞中以1nM进行的以上243种KRAS靶向性DsiRNA的测定揭露下表9中提供的KRAS抑制功效。使用定位于KRAS转录物内不同位置处的成对qPCR测定来测定KRAS水平(对于HeLa细胞实验,qPCR测定指示为“Hs KRAS268-385(MAX)”和“Hs KRAS3393-3516(FAM)”;对于Hepa1-6细胞实验,这种测定指示为“Mm KRAS279-390(MAX)”和“Mm KRAS1064-1161(FAM)”)。
如表9中所示,在用于测定人KRAS水平的两种qPCR测定中,所检验的243种不对称DsiRNA中有103种在1nM时在HeLa细胞中显示人KRAS水平降低超过70%。在这103种DsiRNA中,有37种在用于测定人KRAS水平的两种qPCR测定中在1nM时于HeLa细胞中表现超过80%的人KRAS水平降低。在这些测定中,还鉴定出很多也能够在1nM时于小鼠Hepa1-6细胞的细胞环境中抑制小鼠KRAS水平的不对称DsiRNA。
随后在二次测定(“第2阶段”)中检验上述实验的120种不对称DsiRNA,其中将这些测定的结果呈现于图12-31的柱形图中。具体而言,在人HeLa细胞环境中,评估从以上测试的243种不对称DsiRNA中选出的120种不对称DsiRNA在1nM、0.1nM和0.1nM时对人KRAS的抑制作用(0.1nM以两个重复进行,对每一靶向KRAS的不对称DsiRNA用单独的测定)(图12-21)。另外,还在小鼠Hepa1-6细胞环境中,评估这120种不对称DsiRNA在1nM、0.1nM和0.1nM时对小鼠KRAS的抑制作用(0.1nM也是以两个重复进行,对每一靶向KRAS的不对称DsiRNA用单独的测定)(图22-31)。如图12-21所示,当在HeLa细胞环境中测定时,相当数量的不对称DsiRNA在100pM时可重现地呈现稳固的人KRAS抑制功效。此外,如图22-31中所示,当在小鼠Hepa1-6细胞环境中测定时,这些不对称DsiRNA中有很多也在1nM和100pM时显示出稳固的小鼠KRAS抑制功效。(同时,还鉴定出人KRAS特异性抑制性不对称DsiRNA。)
实施例7:利用其它优选的DsiRNA抑制KRAS
如上文所述,设计并合成表4-5中所示的具有所示有义链和反义链序列并且靶向KRAS野生型序列(且适当时,靶向变体序列)的其余DsiRNA分子,并且如上文实施例3和实施例6中所述在HeLa细胞(且任选在小鼠Hepa1-6细胞)中测试其抑制功效。与相应的针对KRAS靶序列的21mer siRNA相比较任选地评估这些DsiRNA试剂抑制KRAS表达的能力(与用于表2的siRNA序列相同的21mer siRNA鉴别方法可应用于表4-6的DsiRNA)。预期表4-6中的其余所选DsiRNA试剂可显示作为KRAS抑制剂的功效,其中预期相当数量的测试的DsiRNA试剂在1nM和100pM时表现超过50%的KRAS靶降低。如从表2-3的DsiRNA试剂可以看出,预期绝大部分的DsiRNA优于同源siRNA对,如通过测量相对于同源siRNA试剂在降低KRAS靶水平方面的功效来确定。另外,在以0.1nM、1nM和5nM测试浓度施用后24小时和48小时,检验这些抑制作用的持续时间。如上文所述,如通过测量效力和作用持续时间可以确定,预期绝大多数DsiRNA都优于其同源siRNA对。
实施例8:适应症
目前在KRAS研究方面的知识体系指示需要用于测定KRAS活性的方法以及能够调控KRAS表达以供研究、诊断和治疗用途的化合物。如本文所述,本发明的核酸分子可用于多种测定中以诊断与KRAS水平有关的疾病状态。此外可以使用核酸分子来治疗与KRAS错误调控、水平等有关的疾病状态。
与KRAS表达调节相关的特定病症和疾病包括但不限于,癌症和/或增生性疾病、病况或病症,以及与细胞或组织中KRAS水平有关或将对细胞或组织中KRAS水平反应的其它疾病、病况或病症,都可用单独本发明的核酸分子或结合其它疗法治疗。与KRAS表达调节相关的特定退化和疾病状态包括但不限于,例如肺癌、结肠直肠癌、膀胱癌、胰腺癌、乳腺癌和前列腺癌。
吉西他滨(Gemcytabine)和环磷酰胺是可组合或结合本发明的核酸分子(例如DsiRNA分子)使用的化疗剂的非限制性实例。本领域技术人员将认识到,其它药物(如抗癌化合物和疗法)易于以类似方式与本发明的核酸分子(例如,DsiRNA分子)组合,并因此在本发明的范围内。本领域中熟知这些化合物和疗法(参见例如,Cancer:Principles andPractice of Oncology,第1和2卷,Devita,V.T.,Hellman,S.和Rosenberg,S.A.编著,J.B.Lippincott Company,Philadelphia,USA),并且包括但不限于:抗叶酸剂;氟嘧啶;阿糖胞苷;嘌呤类似物;腺苷类似物类;安吖啶;拓扑异构酶I抑制剂;蒽吡唑(anthrapyrazoles);类视黄醇;抗生素,例如博莱霉素、蒽环霉素(anthacyclins)、丝裂霉素C、放线菌素(dactinomycin)和光神霉素(mithramycin);六甲密胺(hexamethylmelamine);达卡巴嗪(dacarbazine);1-天冬酰胺酶;铂类似物类;烷基化剂,例如氮芥(nitrogen mustard)、美法兰(melphalan)、苯丁酸氮芥(chlorambucil)、白消安(busulfan)、异环磷酰胺(ifosfamide)、4-氢过氧环磷酰胺、亚硝基脲、噻替派(thiotepa);植物源性化合物,例如长春花生物碱类、表鬼臼毒素(epipodophyllotoxins)、紫杉酚;它莫西芬(Tamoxifen);辐射疗法;手术;营养补充;基因疗法;放射疗法,例如3D-CRT;免疫毒素疗法,例如蓖麻毒素、单克隆抗体Herceptin等。对于组合疗法,本发明的核酸是以两种方式中的一种制备。第一,在制备核酸和化疗剂时,以物理方式组合各试剂,例如供静脉内施用的囊封在脂质体中的本发明核酸与溶于溶液中的异环磷酰胺的混合物,其中两种试剂都以治疗有效的浓度提供(例如,溶于溶液中的异环磷酰胺是按1000-1250mg/m2/天递送,且溶于相同溶液中的脂质体缔合的本发明核酸按0.1-100mg/kg/天递送)。或者,各试剂各自按其有效剂量(例如,1000-1250mg/m2/d异环磷酰胺和0.1至100mg/kg/天本发明的核酸)单独但同时施用。
本领域技术人员将认识到,用于治疗本文所述疾病和病况的其它化合物和疗法可按类似方式与本发明的核酸分子(例如,siNA分子)组合,并因此都在本发明的范围内。
实施例9:DsiRNA的血清稳定性
通过在37℃下,于50%胎牛血清中孵育DsiRNA试剂多个时间段(最多24小时),来评估DsiRNA试剂的血清稳定性。提取血清,并在20%非变性PAGE上分离核酸,且通过Gelstar染色进行观察。评估保护DsiRNA(任选存在和不存在修饰)免受核酸酶降解的相对水平。
实施例10:使用其它细胞培养模型来评估KRAS基因表达的下调
在细胞培养模型中,已经使用了多种终点来研究用抗Ras试剂处理后Ras介导的作用。表型终点包括细胞增殖、RNA表达的抑制以及Ras蛋白质表达的降低。由于KRAS癌基因突变与某些肿瘤细胞增殖增加直接相关,故优选使用增殖终点作为细胞培养测定的初次筛选。有几种方法可以测量这一终点。在用DsiRNA处理细胞后,使细胞生长(通常5天),随后测量细胞活力、细胞DNA中[3H]胸苷的并入和/或细胞密度。细胞密度的测定可以在96孔格式中使用商购获得的荧光核酸染色剂(例如)进行。可以使用KRas特异性ELISA评估DsiRNA介导的KRas蛋白质表达水平降低作为第二确定性终点。
实施例11:KRAS错误调控的小鼠模型中抗KRAS DsiRNA功效的评估
从体外测定中选择的抗KRAS DsiRNA可以在小鼠模型(包括例如异种移植物和上文所述其它动物模型)中进一步测试。在一个实施例中,通过水动力尾静脉注射对具有错误调控的(例如,升高的)KRAS水平的小鼠施用本发明的DsiRNA试剂。对每组3-4只小鼠(根据测试的特定DsiRNA试剂分组)注射50μg或200μg DsiRNA。使用RT-qPCR评估KRAS RNA水平。另外或或者,可以使用本领域公认的方法来评估KRas水平(例如,KRas蛋白质水平和/或癌细胞/肿瘤形成、生长或扩散),或者监测与KRAS错误调控有关的表型(例如,肿瘤形成、生长、转移等)(任选作为测量KRAS转录物或KRas蛋白质水平的代表)。随后,还可以在这些动物模型中测试活性DsiRNA与标准化疗的组合。
实施例12:诊断用途
本发明的DsiRNA分子可以用于多种诊断应用中,例如,在如临床、工业、环境、农业和/或研究环境等多种应用中鉴别分子靶(例如,RNA)。DsiRNA分子的这些诊断用途涉及利用重建的RNAi系统,例如,使用细胞裂解物或部分纯化的细胞裂解物。本发明的DsiRNA分子可用作诊断工具,以检验患病细胞内的遗传漂变和突变。DsiRNA活性与靶KRAS RNA结构之间的密切关系使得能检测KRAS分子区域中的突变,此改变靶KRAS RNA的碱基配对和三维结构。通过使用多种本发明中所述的DsiRNA分子,技术人员将能够在体外以及细胞和组织中标示出对RNA结构和功能至关重要的核苷酸改变。可以通过用DsiRNA分子裂解靶KRASRNA来抑制基因表达,并确定特定基因产物在KRAS相关性疾病或病症进展方面的作用。按此方式,也可以将其它遗传靶确定为该疾病的重要介体。这些实验通过提供组合疗法的可能性(例如,多种靶向不同基因的DsiRNA分子、与已知的小分子抑制剂结合的DsiRNA分子,或用DsiRNA分子组合进行的间歇性治疗,和/或其它化学或生物分子),将引起对疾病进展的更好治疗。本领域中熟知本发明DsiRNA分子的其它体外用途,并且这些用途包括检测与某一疾病或相关病况有关的RNA的存在。可以在用DsiRNA治疗后,通过使用如荧光共振放射转移(FRET)等标准方法测定裂解产物的存在,来检测该RNA。
在一个特定实施例中,将只裂解野生型或者突变型或多态性靶KRAS RNA的DsiRNA分子用于测定。第一种DsiRNA分子(即,只裂解野生型靶KRAS RNA的DsiRNA分子)用于鉴定样品中存在的野生型KRAS RNA,而第二种DsiRNA分子(即,只裂解突变型或多态性靶RNA的DsiRNA分子)用于鉴定样品中的突变型或多态性KRAS RNA。用两种DsiRNA分子裂解野生型和突变型或多态性KRAS RNA的合成底物作为反应对照,以说明在“非靶”KRAS RNA种类裂解反应和不存在下的相对DsiRNA功效。由合成底物得到的裂解产物也用于产生供分析样品群中野生型和突变型KRAS RNA的尺寸标记物。因此,每一分析都需要两种DsiRNA分子、两种底物和一种未知样品,由此组合成六个反应。裂解产物的存在是使用RNase保护测定所确定,因此可以在聚丙烯酰胺凝胶的一个泳道中分析各KRAS RNA的全长和裂解片段。未必完全需要定量这些结果以了解靶细胞中突变型或多态性KRAS RNA的表达以及KRAS相关性表型改变的假定风险。蛋白质产物涉及到表型(即,疾病相关的/有关的)的发展的KRAS mRNA的表达足以确定风险。如果使用对两种转录物具有相当的比活性的探针,那么KRAS RNA水平的定性比较足够,并且可以降低初始诊断的成本。较高的突变型或多态性与野生型比率与定性还是定量比较KRAS RNA水平的较高风险有关。
本说明书中提到的所有专利和出版物都指示本发明所属领域技术人员的技术水平。本公开中引用的所有参考文献都以引用的方式并入本文中,引用的程度如同将各参考文献独立地以引用的方式整体并入本文中。
本领域技术人员将易于了解,本发明可较好地适于达到所提及的目的并获得所提及的以及其中固有的结果和益处。作为当前优选实施方案的代表的本文所述的方法和组合物是示例性的,并且不旨在限制本发明的范围。本领域技术人员可想到这些方法和组合物的改变和其它用途,这些都涵盖在由权利要求的范围所界定的本发明的精神范围内。
对本领域中的技术人员显而易见的是,在不背离本发明的范围和精神的情况下,可对本文公开的发明进行不同取代和修改。因此,这些其它实施方案也在本发明和所附权利要求的范围内。本发明教导本领域中的技术人员测试本文所述化学修饰的各种组合和/或取代,以产生具有改进的介导RNAi活性的核酸构建体。该改进的活性可包含改进的稳定性、改进的生物利用率和/或改进的介导RNAi的细胞反应的激活作用。因此,本文所述的具体实施方案不是限制性的,并且本领域中的技术人员可容易地了解到,无需过多实验,就能测试本文所述修饰的特定组合,从而鉴别出具有改进的RNAi活性的DsiRNA分子。
本文中说明性描述的本发明宜在不存在本文中未特别公开的任何一种或多种要素、一种或多种限制的情况下实施。因此,例如,在本文各情形中,术语“包含”、“实质上由……组成”和“由……组成”中任一者都可以用其它两个术语中的任一者替代。已采用的这些术语和表述是用作术语的描述而不是限制,并且不旨在使用这些术语和表述排除所示和所描述的特征或其部分的任何等同物,但应认识到,在所要求的本发明的范围内的各种修改都是可能的。因此,应了解,尽管已经通过优选的实施方案具体地公开了本发明,但本领域中的技术人员可以采用本文公开的观念的任选的特征、修改和变更,而且认为这些修改和变更在描述和所附权利要求所界定的范围内。
此外,在按照马库什组(Markush group)或另一替代性分组描述本发明的特征或方面时,本领域中的技术人员应认识到,同样可据此按照该马库什组或其它组的任一个别成员或成员小组来描述本发明。
除非本文中另外指明或上下文明显矛盾,否则在描述本发明的上下文中(尤其是以下权利要求的上下文中)使用的术语“一个”、“一种”和“所述”以及相似的指代词语应解释为涵盖单数和复数。除非另外说明,否则术语“包含”、“具有”、“包括”和“含有”应解释为开放式术语(即,表示“包括但不限于”之意)。本文中值的范围的列举仅旨在用作单独提及该范围内的各单独值的简写方法,除非本文中另外指明,否则各单独值都并入本说明书中,如同在本文中对其单独列举一样。除非本文中另外指明或上下文明显矛盾,否则本文描述的所有方法可按任何适合的次序进行。除非另外要求,否则对本文中提供的任何和所有实施例或示例性语言(例如,“如”)的使用都仅旨在更好阐述本发明,而不是对本发明或权利要求的范围构成限制。说明书中没有语言应解释为指示任何非要求元素对于本发明的实施是必不可少的。
本文描述了本发明的实施方案,包括为本发明人所知用于实施本发明的最佳方式。在阅读了上述描述后,这些所述实施方案的变化对本领域的技术人员将变得显而易见。
本发明人预期熟练技术人员会酌情采用此类变化,而且本发明人希望能以除了本文具体描述的方式之外的方式来实施。因此,在适用法律允许的情况下,本发明包括对本文所附权利要求中陈述的主题进行的所有修改和等同物。此外,除非本文另外指明或上下文明显矛盾,否则其所有可能变化的任何上述要素组合都涵盖在本发明内。本领域中的技术人员仅仅使用常规实验就将认识到或能够确定本文所述本发明的具体实施方案的许多等同物。意图将这些等同物涵盖在以上权利要求中。

Claims (13)

1.一种用于降低KRAS靶基因表达的分离的双链核糖核酸(dsRNA),其中,所述dsRNA为SEQ ID NO:108组成的第一条链和SEQ ID NO:29组成的第二条链,或者,SEQ ID NO:4695组成的第一条链和SEQ ID NO:4452组成的第二条链。
2.根据权利要求1所述的分离的dsRNA,其中从所述第一寡核苷酸链3'末端的第一个核苷酸(1位)开始,使1位、2位和/或3位的核苷酸被修饰。
3.根据权利要求1所述的分离的dsRNA,其中所述第一条链是SEQ ID NO:108并且第二条链的序列是SEQ ID NO:29。
4.根据权利要求1所述的分离的dsRNA,其中所述第一条链是SEQ ID NO:4695并且第二条链的序列是SEQ ID NO:4452。
5.根据权利要求2所述的分离的dsRNA,所述修饰包含选自由以下组成的组:脱氧核糖核苷酸、双脱氧核糖核苷酸、无环核苷酸、3'-脱氧腺苷(虫草素)、3'-叠氮基-3'-脱氧胸苷(AZT)、2',3'-双脱氧肌苷(ddI)、2',3'-双脱氧-3'-硫代胞苷(3TC)、2',3'-双脱氢-2',3'-双脱氧胸苷(d4T)、3'-叠氮基-3'-脱氧胸苷(AZT)的单磷酸核苷酸、2',3'-双脱氧-3'-硫代胞苷(3TC)和2',3'-双脱氢-2',3'-双脱氧胸苷(d4T)的单磷酸核苷酸、4-硫代尿嘧啶、5-溴尿嘧啶、5-碘尿嘧啶、5-(3-氨基烯丙基)-尿嘧啶、2'-O-烷基核糖核苷酸、2'-O-甲基核糖核苷酸、2'-氨基核糖核苷酸、2'-氟核糖核苷酸和锁核酸。
6.根据权利要求1所述的分离的dsRNA,其包含选自由磷酸酯、硫代磷酸酯和磷酸三酯组成的组的磷酸骨架修饰。
7.权利要求1-6任一项所述的分离的dsRNA在制备用于降低哺乳动物中KRAS靶基因表达的药剂中的应用。
8.权利要求1-6任一项所述的分离的dsRNA在制备用于选择性抑制细胞生长的药剂中的应用。
9.根据权利要求8所述的应用,其中所述细胞是受试者的肿瘤细胞。
10.根据权利要求8所述的应用,其中所述细胞是体外肿瘤细胞。
11.根据权利要求8所述的应用,其中所述细胞是人细胞。
12.一种药物组合物,其包含权利要求1-6任一项所述的分离的dsRNA和药学上可接受的载体。
13.一种试剂盒,其包括权利要求12所述的药物组合物。
CN201310485274.XA 2009-04-03 2010-04-05 利用不对称双链rna特异性抑制kras的方法和组合物 Active CN103555722B (zh)

Applications Claiming Priority (33)

Application Number Priority Date Filing Date Title
US16655909P 2009-04-03 2009-04-03
US16657809P 2009-04-03 2009-04-03
US61/166,559 2009-04-03
US61/166,578 2009-04-03
US17430609P 2009-04-30 2009-04-30
US17427909P 2009-04-30 2009-04-30
US61/174,279 2009-04-30
US61/174,306 2009-04-30
US18381509P 2009-06-03 2009-06-03
US18381809P 2009-06-03 2009-06-03
US61/183,818 2009-06-03
US61/183,815 2009-06-03
US18473509P 2009-06-05 2009-06-05
US61/184,735 2009-06-05
PCT/US2009/005214 WO2010033225A2 (en) 2008-09-22 2009-09-17 Compositions and methods for the specific inhibition of gene expression by dsrna possessing modifications
USPCT/US2009/005214 2009-09-17
US25782009P 2009-11-03 2009-11-03
US25781009P 2009-11-03 2009-11-03
US61/257,820 2009-11-03
US61/257,810 2009-11-03
US28592509P 2009-12-11 2009-12-11
US61/285,925 2009-12-11
US12/642,264 2009-12-18
US12/642,371 2009-12-18
US12/642,371 US8513207B2 (en) 2008-12-18 2009-12-18 Extended dicer substrate agents and methods for the specific inhibition of gene expression
US12/642,264 US20100173973A1 (en) 2008-12-18 2009-12-18 Extended dicer substrate agents and methods for the specific inhibition of gene expression
US12/642,404 2009-12-18
US12/642,404 US20100184841A1 (en) 2008-12-18 2009-12-18 Extended dicer substrate agents and methods for the specific inhibition of gene expression
US12/704,256 2010-02-11
US12/704,256 US20100249214A1 (en) 2009-02-11 2010-02-11 Multiplex dicer substrate rna interference molecules having joining sequences
US30926610P 2010-03-01 2010-03-01
US61/309,266 2010-03-01
CN201080024105.0A CN102575254B (zh) 2009-04-03 2010-04-05 利用不对称双链rna特异性抑制kras的方法和组合物

Related Parent Applications (1)

Application Number Title Priority Date Filing Date
CN201080024105.0A Division CN102575254B (zh) 2009-04-03 2010-04-05 利用不对称双链rna特异性抑制kras的方法和组合物

Publications (2)

Publication Number Publication Date
CN103555722A CN103555722A (zh) 2014-02-05
CN103555722B true CN103555722B (zh) 2016-08-31

Family

ID=42828984

Family Applications (3)

Application Number Title Priority Date Filing Date
CN201080024105.0A Active CN102575254B (zh) 2009-04-03 2010-04-05 利用不对称双链rna特异性抑制kras的方法和组合物
CN201510043324.8A Pending CN104651362A (zh) 2009-04-03 2010-04-05 利用不对称双链rna特异性抑制kras的方法和组合物
CN201310485274.XA Active CN103555722B (zh) 2009-04-03 2010-04-05 利用不对称双链rna特异性抑制kras的方法和组合物

Family Applications Before (2)

Application Number Title Priority Date Filing Date
CN201080024105.0A Active CN102575254B (zh) 2009-04-03 2010-04-05 利用不对称双链rna特异性抑制kras的方法和组合物
CN201510043324.8A Pending CN104651362A (zh) 2009-04-03 2010-04-05 利用不对称双链rna特异性抑制kras的方法和组合物

Country Status (13)

Country Link
US (5) US8372816B2 (zh)
EP (3) EP3199165B1 (zh)
JP (1) JP6010458B2 (zh)
KR (1) KR101791702B1 (zh)
CN (3) CN102575254B (zh)
AU (1) AU2010232410B2 (zh)
CA (1) CA2757613C (zh)
DK (2) DK2756845T3 (zh)
ES (2) ES2628144T3 (zh)
HU (1) HUE059432T2 (zh)
PL (1) PL3199165T3 (zh)
PT (1) PT3199165T (zh)
WO (1) WO2010115206A2 (zh)

Families Citing this family (43)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9657294B2 (en) 2002-02-20 2017-05-23 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US9181551B2 (en) 2002-02-20 2015-11-10 Sirna Therapeutics, Inc. RNA interference mediated inhibition of gene expression using chemically modified short interfering nucleic acid (siNA)
US20060134787A1 (en) * 2004-12-22 2006-06-22 University Of Massachusetts Methods and compositions for enhancing the efficacy and specificity of single and double blunt-ended siRNA
EP2756845B1 (en) * 2009-04-03 2017-03-15 Dicerna Pharmaceuticals, Inc. Methods and compositions for the specific inhibition of KRAS by asymmetric double-stranded RNA
JP6010458B2 (ja) 2009-04-03 2016-10-19 ダイセルナ ファーマシューティカルズ, インコーポレイテッドDicerna Pharmaceuticals, Inc. 非対称二本鎖rnaによる特異的阻害のための、方法および組成物
US20120114710A1 (en) * 2009-05-18 2012-05-10 Lynn Kirkpatrick Carbon nanotubes complexed with multiple bioactive agents and methods related thereto
US20150025122A1 (en) * 2009-10-12 2015-01-22 Larry J. Smith Methods and Compositions for Modulating Gene Expression Using Oligonucleotide Based Drugs Administered in vivo or in vitro
US9200326B2 (en) * 2009-12-07 2015-12-01 Arkray, Inc. Probe for detecting polymorphism in disease-related gene and use of the probe
WO2012053741A2 (ko) * 2010-10-22 2012-04-26 성균관대학교산학협력단 Rna 간섭을 유도하는 핵산 분자 및 그 용도
EP3766975A1 (en) 2010-10-29 2021-01-20 Sirna Therapeutics, Inc. Rna interference mediated inhibition of gene expression using short interfering nucleic acid (sina)
CN103987847B (zh) 2011-10-18 2017-06-16 迪克纳制药公司 胺阳离子脂质及其用途
EA201492004A1 (ru) * 2012-05-02 2015-08-31 Новартис Аг Органические композиции для лечения kras-ассоциированных заболеваний
EP2853597B1 (en) 2012-05-22 2018-12-26 Olix Pharmaceuticals, Inc. Rna-interference-inducing nucleic acid molecule able to penetrate into cells, and use therefor
WO2014013995A1 (ja) 2012-07-16 2014-01-23 協和発酵キリン株式会社 KRAS遺伝子発現抑制RNAi医薬組成物
KR102205278B1 (ko) 2013-03-14 2021-01-22 다이서나 파마수이티컬, 인크. 음이온성 약제를 제형화하는 방법
EP3444350B1 (en) 2013-07-03 2021-12-01 Dicerna Pharmaceuticals, Inc. Methods and compositions for the specific inhibition of alpha-1 antitrypsin by double-stranded rna
KR101670254B1 (ko) * 2014-07-09 2016-10-28 서울대학교산학협력단 목적 유전자의 발현 억제 특이성이 증가된 siRNA 분자
US9950194B2 (en) 2014-09-09 2018-04-24 Mevion Medical Systems, Inc. Patient positioning system
PL3234134T3 (pl) 2014-12-17 2020-12-28 Proqr Therapeutics Ii B.V. Ukierunkowana edycja rna
CN108699556B (zh) 2015-11-16 2023-02-17 奥利克斯医药有限公司 使用靶向myd88或tlr3的rna复合物治疗老年性黄斑变性
US10619159B2 (en) 2016-01-19 2020-04-14 The University Of North Carolina At Chapel Hill Methods and compositions using RNA interference for inhibition of KRAS
US11180759B2 (en) 2016-01-19 2021-11-23 The University Of North Carolina At Chapel Hill Methods and compositions using RNA interference and antisense oligonucleotides for inhibition of KRAS
US10519449B2 (en) 2016-02-02 2019-12-31 Olix Pharmaceuticals, Inc. Treatment of angiogenesis-associated diseases using RNA complexes that target ANGPT2 and PDGFB
CA3022874A1 (en) 2016-02-02 2017-08-10 Olix Pharmaceuticals, Inc. Treatment of atopic dermatitis and asthma using rna complexes that target il4ra, trpa1, or f2rl1
MA45470A (fr) * 2016-04-01 2019-02-06 Avidity Biosciences Llc Acides nucléiques kras et leurs utilisations
CN105858567A (zh) * 2016-04-15 2016-08-17 北京华绿生物科技有限公司 食用菌菌瓶的扣盖稳定器、食用菌菌瓶压盖设备
AU2017281497B2 (en) 2016-06-22 2023-04-06 Proqr Therapeutics Ii B.V. Single-stranded RNA-editing oligonucleotides
KR101916652B1 (ko) 2016-06-29 2018-11-08 올릭스 주식회사 작은 간섭 rna의 rna 간섭효과 증진용 화합물 및 이의 용도
CN107460197A (zh) * 2016-08-18 2017-12-12 广州市锐博生物科技有限公司 用于抑制COPS5靶基因mRNA表达的寡核酸分子及其成套组合物
KR102501980B1 (ko) 2016-09-01 2023-02-20 프로큐알 테라퓨틱스 Ⅱ 비.브이. 화학적으로 변형된 단일 가닥 rna-편집 올리고뉴클레오타이드
EP4035659A1 (en) 2016-11-29 2022-08-03 PureTech LYT, Inc. Exosomes for delivery of therapeutic agents
US11274300B2 (en) 2017-01-19 2022-03-15 Proqr Therapeutics Ii B.V. Oligonucleotide complexes for use in RNA editing
EP3580339A4 (en) 2017-02-10 2020-12-23 Research & Business Foundation Sungkyunkwan University LONG DOUBLE STRAND RNA FOR RNA INTERFERENCE
TW202003846A (zh) * 2018-02-12 2020-01-16 美商科迪亞克生物科學股份有限公司 用於巨噬細胞極化之方法及組合物
EP4268832A3 (en) 2018-03-27 2024-03-06 ProQR Therapeutics II B.V. Nucleic acid molecules for pseudouridylation
KR20200144100A (ko) * 2018-04-13 2020-12-28 다이서나 파마수이티컬, 인크. Tm-증가 뉴클레오타이드로 변형된 이중-가닥 핵산 억제제 분자
CA3134486A1 (en) 2019-03-29 2020-10-08 Dicerna Pharmaceuticals, Inc. Compositions and methods for the treatment of kras associated diseases or disorders
US11781138B2 (en) * 2019-10-14 2023-10-10 Aro Biotherapeutics Company FN3 domain-siRNA conjugates and uses thereof
CN110981943B (zh) * 2019-12-02 2021-08-03 清华大学 多肽及其在制备药物中的用途和药物
WO2021207339A1 (en) * 2020-04-07 2021-10-14 The University Of North Carolina At Chapel Hill Methods and compositions using rna interference and antisense oligonucleotides for inhibition of kras
CN111534520A (zh) * 2020-05-27 2020-08-14 深圳市疾病预防控制中心(深圳市卫生检验中心、深圳市预防医学研究所) 特异抑制K-ras基因表达的慢病毒和重组载体构建及其应用
KR102379204B1 (ko) * 2020-12-18 2022-03-24 이화여자대학교 산학협력단 유전자 침묵 활성이 증가된 핵산 분자 및 이의 이용
AU2022258566A1 (en) 2021-04-14 2023-10-12 Aro Biotherapeutics Company Cd71 binding fibronectin type iii domains

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004045543A2 (en) * 2002-11-14 2004-06-03 Dharmacon, Inc. Functional and hyperfunctional sirna
WO2005078095A1 (en) * 2004-02-06 2005-08-25 Dharmacon, Inc. SNP DISCRIMINATORY siRNA
WO2009029688A2 (en) * 2007-08-27 2009-03-05 Boston Biomedical, Inc. Compositions of asymmetric interfering rna and uses thereof

Family Cites Families (28)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5432272A (en) 1990-10-09 1995-07-11 Benner; Steven A. Method for incorporating into a DNA or RNA oligonucleotide using nucleotides bearing heterocyclic bases
WO1992007065A1 (en) 1990-10-12 1992-04-30 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Modified ribozymes
US5652094A (en) 1992-01-31 1997-07-29 University Of Montreal Nucleozymes
CA2135499A1 (en) * 1992-05-14 1993-11-25 James D. Thompson Method and reagent for inhibiting cancer development
US6218108B1 (en) 1997-05-16 2001-04-17 Research Corporation Technologies, Inc. Nucleoside analogs with polycyclic aromatic groups attached, methods of synthesis and uses therefor
EP0843019A3 (en) * 1996-11-08 2002-10-09 Kyowa Medex Co., Ltd. Method for determination of specific nucleic acid sequence, and a reagent therefor
US6248878B1 (en) 1996-12-24 2001-06-19 Ribozyme Pharmaceuticals, Inc. Nucleoside analogs
US6506559B1 (en) * 1997-12-23 2003-01-14 Carnegie Institute Of Washington Genetic inhibition by double-stranded RNA
US7829693B2 (en) * 1999-11-24 2010-11-09 Alnylam Pharmaceuticals, Inc. Compositions and methods for inhibiting expression of a target gene
US20050288242A1 (en) * 2001-05-18 2005-12-29 Sirna Therapeutics, Inc. RNA interference mediated inhibition of RAS gene expression using short interfering nucleic acid (siNA)
US20040121348A1 (en) * 2001-10-26 2004-06-24 Ribopharma Ag Compositions and methods for treating pancreatic cancer
CN1608131A (zh) * 2001-10-26 2005-04-20 里伯药品公司 治疗胰腺癌的药物
EP1675949A2 (en) * 2003-10-23 2006-07-05 Sirna Therapeutics, Inc. RNA INTERFERENCE MEDIATED INHIBITION OF NOGO AND NOGO RECEPTOR GENE EXPRESSION USING SHORT INTERFERING NUCLEIC ACID (siNA)
US20050277610A1 (en) 2004-03-15 2005-12-15 City Of Hope Methods and compositions for the specific inhibition of gene expression by double-stranded RNA
US20070265220A1 (en) 2004-03-15 2007-11-15 City Of Hope Methods and compositions for the specific inhibition of gene expression by double-stranded RNA
US20080213891A1 (en) 2004-07-21 2008-09-04 Alnylam Pharmaceuticals, Inc. RNAi Agents Comprising Universal Nucleobases
WO2007030167A1 (en) 2005-09-02 2007-03-15 Nastech Pharmaceutical Company Inc. Modification of double-stranded ribonucleic acid molecules
WO2007031091A2 (en) * 2005-09-15 2007-03-22 Santaris Pharma A/S Rna antagonist compounds for the modulation of p21 ras expression
JP4644619B2 (ja) 2006-03-27 2011-03-02 富士通株式会社 基地局装置、端末および帯域制御方法
JP2009531068A (ja) * 2006-03-27 2009-09-03 グローブイミューン,インコーポレイテッド Ras変異並びにこれに関連する組成物及び方法
WO2008109516A2 (en) * 2007-03-02 2008-09-12 Mdrna, Inc. Nucleic acid compounds for inhibiting ras gene expression and uses thereof
US20100105134A1 (en) * 2007-03-02 2010-04-29 Mdrna, Inc. Nucleic acid compounds for inhibiting gene expression and uses thereof
JP2010529834A (ja) * 2007-05-21 2010-09-02 デイナ ファーバー キャンサー インスティチュート,インコーポレイテッド 癌遺伝子の発見のための組成物および方法
JP2010538678A (ja) * 2007-09-18 2010-12-16 イントラドイグム コーポレーション K−rassiRNA含有組成物及びそれらの使用法
WO2010020618A1 (en) * 2008-08-18 2010-02-25 MAX-PLANCK-Gesellschaft zur Förderung der Wissenschaften e.V. Susceptibility to hsp90-inhibitors
CN101381779B (zh) * 2008-10-21 2011-06-08 广州益善生物技术有限公司 kRas基因突变的检测探针、液相芯片及其检测方法
JP6010458B2 (ja) * 2009-04-03 2016-10-19 ダイセルナ ファーマシューティカルズ, インコーポレイテッドDicerna Pharmaceuticals, Inc. 非対称二本鎖rnaによる特異的阻害のための、方法および組成物
WO2014013995A1 (ja) * 2012-07-16 2014-01-23 協和発酵キリン株式会社 KRAS遺伝子発現抑制RNAi医薬組成物

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004045543A2 (en) * 2002-11-14 2004-06-03 Dharmacon, Inc. Functional and hyperfunctional sirna
WO2005078095A1 (en) * 2004-02-06 2005-08-25 Dharmacon, Inc. SNP DISCRIMINATORY siRNA
WO2009029688A2 (en) * 2007-08-27 2009-03-05 Boston Biomedical, Inc. Compositions of asymmetric interfering rna and uses thereof

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
K-ras oncogene silencing strategy reduces tumor growth and enhances gemcitabine chemotherapy efficacy for pancreatic cancer treatment;Soukaina Rejiba et al.;《Cancer Science》;20070701;第1128-1136页 *

Also Published As

Publication number Publication date
US20110021604A1 (en) 2011-01-27
DK3199165T3 (da) 2022-07-11
US9200284B2 (en) 2015-12-01
US20200318118A1 (en) 2020-10-08
EP2414374A4 (en) 2013-09-25
PT3199165T (pt) 2022-07-13
CN102575254A (zh) 2012-07-11
JP6010458B2 (ja) 2016-10-19
US9809819B2 (en) 2017-11-07
CN104651362A (zh) 2015-05-27
EP3199165B1 (en) 2022-06-08
DK2756845T3 (en) 2017-06-12
EP3199165A1 (en) 2017-08-02
EP4124657A2 (en) 2023-02-01
US20180044680A1 (en) 2018-02-15
US8372816B2 (en) 2013-02-12
HUE059432T2 (hu) 2022-11-28
US20150057337A1 (en) 2015-02-26
US10752899B2 (en) 2020-08-25
CA2757613C (en) 2023-10-17
WO2010115206A3 (en) 2010-11-25
AU2010232410B2 (en) 2016-11-17
US11447777B2 (en) 2022-09-20
EP4124657A3 (en) 2023-05-03
KR101791702B1 (ko) 2017-10-30
CA2757613A1 (en) 2010-10-07
CN103555722A (zh) 2014-02-05
US20130123342A1 (en) 2013-05-16
ES2921573T3 (es) 2022-08-29
EP2414374A2 (en) 2012-02-08
ES2628144T3 (es) 2017-08-01
JP2012531888A (ja) 2012-12-13
AU2010232410A1 (en) 2011-10-27
KR20120034610A (ko) 2012-04-12
CN102575254B (zh) 2015-03-04
PL3199165T3 (pl) 2022-09-05
WO2010115206A2 (en) 2010-10-07

Similar Documents

Publication Publication Date Title
CN103555722B (zh) 利用不对称双链rna特异性抑制kras的方法和组合物
CN102325534B (zh) 延长的dicer酶底物和特异性抑制基因表达的方法
EP2756845B1 (en) Methods and compositions for the specific inhibition of KRAS by asymmetric double-stranded RNA
AU2014284298B2 (en) Methods and compositions for the specific inhibition of alpha-1 antitrypsin by double-stranded RNA
CN104968785A (zh) 用于通过双链RNA特异性抑制myc的方法和组合物
ES2875558T3 (es) Métodos y composiciones para la inhibición específica de glicolato oxidasa (HAO1) por ARN de doble cadena
US9428752B2 (en) Methods and compositions for the specific inhibition of beta-catenin by double-stranded RNA
CN102497870A (zh) 肽-dicer底物试剂及其特异性抑制基因表达的方法
US9670488B2 (en) Methods and compositions for the specific inhibition of met by double stranded RNA
WO2016183009A2 (en) Methods and compositions for the specific inhibition of antithrombin 3 (at3) by double-stranded rna
WO2013138668A1 (en) Methods and compositions for the specific inhibition of mcl1 by double-stranded rna
US9850486B2 (en) Methods and compositions for the specific inhibition of CKAP5 by double-stranded RNA

Legal Events

Date Code Title Description
C06 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
C14 Grant of patent or utility model
GR01 Patent grant