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Optimized methods for the synthesis of circular RNA in vitro and in cells, and a complementary Cas9 de-immunization method, enhance RNA persistence and reduce immunogenicity for applications in genome engineering and cell engineering.
The quality of three-dimensional optoacoustic images of subcutaneous microvasculature in patients can be enhanced by reducing the scan times of all-optical Fabry–Pérot scanners to a few seconds.
We computationally designed protein binders for chimeric antigen receptor (CAR) constructs to target the glioblastoma-associated antigens EGFR and CD276. Compared with standard CAR T cells, CAR T cells with the de novo-designed binders showed enhanced proliferation, cytokine release and resistance to exhaustion, as well as superior antitumour effects in vitro and in vivo.
A latent diffusion model pre-trained on pairs of natural images and text descriptors can be adapted to generate realistic chest radiographs that are controlled by free-form medical text prompts.
The nuclease Cas9 and DNA-repair pathway homology-mediated end joining can be leveraged to efficiently and non-virally integrate large DNA payloads into genomic target sites in primary T cells.
An analysis of histopathological data from mouse and human tumours via machine learning reveals that the densities of blood vessels and tumour-associated macrophages are predictive features of the degree of tumoural accumulation of polymeric and liposomal nanomedicines.
This Review discusses genetic-engineering technologies for the rewiring of signalling networks in mammalian cells, including the recombination of native pathway components, cross-kingdom pathway transplantation and the development of de novo signalling.
This Perspective discusses the need for standards that allow for comparisons of quantitative physiological features in microphysiological systems and humans.
The cellular composition of fibrous tissue around orthopaedic implants and the genetic pathways involved in its formation are unclear. We find that leptin-receptor-expressing cells activate the adhesion G-protein-coupled receptor F5 (ADGRF5) pathway to form peri-implant fibrous tissue. Inhibition of ADGRF5 in leptin-receptor-expressing cells can prevent and reverse peri-implant fibrosis.
We have developed a versatile approach for promoting the penetration of commensal bacteria into the intestinal mucosa, by coating the bacterial surface with poly(ethylene glycol) (PEG). PEGylation-enabled penetration facilitated the preferential localization of bacteria at the mucus layer of the intestinal mucosal barrier, thereby reinforcing this barrier.
Fluorescence guidance is utilized to increase the chances of complete tumour resection while balancing preservation of neurological function in glioma surgery. A multimodal optical microscope capable of imaging the histology and fluorescence of fresh human brain specimens revealed an unexpected pattern of fluorophore accumulation and a new means of visualizing macrophages during surgery.
This Review discusses strategies for the design of cell–drug conjugates, the techniques for their preparation, and their translational applications, particularly for the treatment of cancers and autoimmune diseases.
This Perspective examines how metal ions modulate the immune system and host–microbiota interactions, and proposes strategies for the development of metal-ion-based immunotherapies.
The majority of the human non-coding genome remains poorly studied. A user-friendly genome-wide screening system composed of thousands of paired single-guide RNAs for the deletion of non-coding regions revealed key functions of many non-coding elements in cell growth and cell differentiation and in cellular response to drugs.
The physicochemical properties of cationic helical polypeptides can be optimized to induce endoplasmic reticulum stress in antigen-presenting cells so as to elicit antitumour innate immune responses.
The mechanical sensor PIEZO1 regulates the traction force that is critical for cytotoxic T cells to target tumour cells. This finding creates avenues for enhancing the efficacy of T cell-targeted immune therapies.
By coating manganese dioxide on the surface of fixed bacteria, we obtained mineralized bacteria with the ability to potently activate multiple immune signalling pathways. Immunotherapy with mineralized bacteria suppressed various types of cancer in multiple animal models, eliciting both immune memory and abscopal antitumour effects.
CRISPR–Cas12a was used to directly replace mouse antibody variable chain genes with human versions in primary B cells. The edited cells underwent affinity maturation in vivo, improving the potency of HIV-1 and SARS-CoV-2 neutralizing antibodies without loss of bioavailability. Affinity maturation of edited cells also enables new vaccine models and adaptive B cell therapies.
