阿达尔
RNA编辑
核糖核酸
生物
引导RNA
计算生物学
寡核苷酸
肌苷
RNA沉默
小RNA
基因组编辑
细胞生物学
遗传学
DNA
腺苷
RNA干扰
生物化学
清脆的
基因
作者
Liang Qu,Zongyi Yi,Shiyou Zhu,Chunhui Wang,Zhongzheng Cao,Zhuo Zhou,Pengfei Yuan,Ying Yu,Feng Tian,Zhiheng Liu,Ying Bao,Yanxia Zhao,Wensheng Wei
标识
DOI:10.1038/s41587-019-0178-z
摘要
Current tools for targeted RNA editing rely on the delivery of exogenous proteins or chemically modified guide RNAs, which may lead to aberrant effector activity, delivery barrier or immunogenicity. Here, we present an approach, called leveraging endogenous ADAR for programmable editing of RNA (LEAPER), that employs short engineered ADAR-recruiting RNAs (arRNAs) to recruit native ADAR1 or ADAR2 enzymes to change a specific adenosine to inosine. We show that arRNA, delivered by a plasmid or viral vector or as a synthetic oligonucleotide, achieves editing efficiencies of up to 80%. LEAPER is highly specific, with rare global off-targets and limited editing of non-target adenosines in the target region. It is active in a broad spectrum of cell types, including multiple human primary cell types, and can restore α-L-iduronidase catalytic activity in Hurler syndrome patient-derived primary fibroblasts without evoking innate immune responses. As a single-molecule system, LEAPER enables precise, efficient RNA editing with broad applicability for therapy and basic research.
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