北京大学魏文胜研究团队开发出新型RNA编辑技术，其通过使用工程化RNA招募内源性ADAR进行可编程的RNA编辑。2019年9月，《自然—生物技术》发表了这一成果。

研究人员提出了一种称为利用内源性ADAR进行RNA可编程编辑（LEAPER）的方法，采用短的工程化ADAR募集RNA（arRNA）来招募天然ADAR1或ADAR2酶以将特定腺苷转变为肌苷。研究人员发现由质粒或病毒载体或作为合成寡核苷酸递送的arRNA实现高达80％的编辑效率。LEAPER具有高度特异性，在目标区域具有极少的全局性脱靶以及有限的非靶腺苷编辑。它在广谱细胞类型中具有活性，包括多种人原代细胞类型，并且可以在Hurler综合征患者来源的原代成纤维细胞中恢复α-L-艾杜糖醛酸酶催化活性，而不会引起先天免疫反应。作为单分子系统，LEAPER可实现精确、高效的RNA编辑，广泛适用于治疗和基础研究。

研究人员表示，目前靶向RNA编辑的工具依赖于外源蛋白质或化学修饰的向导RNA的递送，这可能导致异常的效应子活性、递送障碍或免疫原性。

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魏文胜，北京大学生命科学学院研究员、博士生导师。致力于发展基因组编辑技术、功能基因组学以及基因治疗；在此基础上研究癌症、感染等重大疾病发生机制，为发展高效治疗手段提供新的药物靶点和思路。（据北京大学）

附：英文原文

Title: Programmable RNA editing by recruiting endogenous ADAR using engineered RNAs

Author: 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

Issue&Volume: Volume 37 Issue 9

Abstract: 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 -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.

DOI: 10.1038/s41587-019-0178-z

Source:https://www.nature.com/articles/s41587-019-0178-z