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BR112021018606A2 - Métodos e composições para editar sequências de nucleotídeos - Google Patents

Métodos e composições para editar sequências de nucleotídeos

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Publication number
BR112021018606A2
BR112021018606A2 BR112021018606A BR112021018606A BR112021018606A2 BR 112021018606 A2 BR112021018606 A2 BR 112021018606A2 BR 112021018606 A BR112021018606 A BR 112021018606A BR 112021018606 A BR112021018606 A BR 112021018606A BR 112021018606 A2 BR112021018606 A2 BR 112021018606A2
Authority
BR
Brazil
Prior art keywords
methods
editing
prime editing
rna
compositions
Prior art date
Application number
BR112021018606A
Other languages
English (en)
Inventor
Vito Anzalone Andrew
R Liu David
James Nelson
Peyton Randolph
Original Assignee
Harvard College
Broad Inst 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
Application filed by Harvard College, Broad Inst Inc filed Critical Harvard College
Publication of BR112021018606A2 publication Critical patent/BR112021018606A2/pt

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Abstract

métodos e composições para editar sequências de nucleotídeos. a presente revelação provê composições e métodos para realizar edição principal de uma molécula de dna alvo (por exemplo, (p.e.) um genoma) que permite a incorporação de uma alteração de nucleotídeo e/ou mutagênese direcionada. a alteração de nucleotídeo pode incluir uma alteração de nucleotídeo único (p.e., qualquer transição ou qualquer transversão), uma inserção de um ou mais nucleotídeos ou uma deleção de um ou mais nucleotídeos. mais em particular, a revelação provê proteínas de fusão compreendendo proteínas de ligação de dna programável de ácido nucleico (napdnabp) e uma polimerase (p.e., transcriptase reversa), que é guiada até uma sequência de dna específica por um rna de guia modificado, chamado pegrna. o pegrna foi alterado (em relação a um rna de guia padrão) para compreender uma parte estendida que provê uma sequência de gabarito de síntese de dna que codifica um flap de dna de fita única, que é homólogo a uma fita da sequência de dna endógena direcionada a ser editada, porém que contém uma ou mais alterações de nucleotídeo pretendidas e que, após síntese pela polimerase (p.e., transcriptase reversa), se torna incorporada na molécula de dna alvo. são também revelados métodos que impulsionam a edição principal, incluindo tratar doenças de contração de repetição de trinucleotídeo, instalar tags de peptídeo direcionado, tratar doença de príon através da instalação de mutações de proteção, manipular genes de codificação de rna para a instalação de tags de rna para controlar a função e expressão de rna, utilizar edição principal para construir bibliotecas sofisticadas de genes, utilizar edição principal para inserir imunoepítopos em proteínas, usar a edição principal para inserir domínios de dimerização induzíveis nos alvos de proteína, e métodos de aplicação, entre outros.
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