Non-immunogenic and Reversible Transgene Expression Using Self-Amplifying RNA

Tony K.Y. Lim,Anne Ritoux, Luke W. Paine,Larissa Ferguson, Tawab Abdul,Ewan St. John Smith

biorxiv（2024）

University of Cambridge | MRC Laboratory of Molecular Biology

Cited 0|Views6

Abstract

Current self-amplifying RNA (saRNA) vectors induce apoptosis and inflammation, restricting their therapeutic potential. By engineering saRNA to co-express viral and cellular inhibitors that target multiple innate immune pathways, we achieve reversible transgene expression while minimizing cytotoxicity and immunogenicity. This advancement enables broader applications for saRNA beyond vaccines, creating opportunities for non-inflammatory RNA-based therapeutics with sustained and reversible transgene expression. ### Competing Interest Statement The authors have declared no competing interest.

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【要点】：研究通过工程化自扩增RNA（saRNA）来共表达病毒和细胞抑制剂，以针对多种先天免疫途径，实现了降低细胞毒性和免疫原性，并达到可逆的转基因表达，为非炎症性RNA基础治疗提供了新的可能性。

【方法】：研究者设计了一种新型的saRNA，该saRNA能够同时表达针对多个免疫通路的病毒和细胞内抑制剂，从而在最小化细胞毒性和免疫原性的同时，实现转基因表达的可逆性。

【实验】：具体实验细节未在摘要中详述，但研究结果表明，通过使用这种工程化的saRNA，可以在不诱导凋亡和炎症的情况下，实现转基因的可逆表达。数据集名称未提及。

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