RNA结构编程内源性ADAR进行精确高效的编辑，这一成果由北京大学魏文胜小组经过不懈努力而取得。2026年6月10日出版的《细胞》杂志发表了这一最新研究成果。

研究人员提出了LEAPER 3.0（利用内源性ADAR对RNA进行可编程编辑），这是下一代RNA编辑平台，将AlphaFold 3结构预测与系统生化和细胞分析相结合，以定义ADAR1或ADAR2与双链RNA之间的分子界面。这些见解使arRNAs的合理优化能够将可编辑序列范围扩展到先前的难编辑位点，抑制双工区域内的旁观者编辑，并实现相邻腺苷之间的单核苷酸区分。这项工作阐明了arRNA介导编辑的结构和机制原理，并为合理设计高效、精确的A-to-I RNA编辑工具建立了框架。

据了解，通过工程化的ADAR招募RNA （arRNAs）利用内源性腺苷脱氨酶（ADAR）提供了一种安全、可编程的RNA编辑策略，无需外源性腺苷脱氨酶递送。然而，对ADAR机制基础的不完全理解阻碍了合理设计arRNA以提高效率和精度。

附：英文原文

Title: RNA structure programs endogenous ADAR for precise and efficient editing

Author: Deli Song, Gexing Liu, Wei Zhang, Jiwu Ren, Xuanxuan Jin, Yanglong Sun, Zexuan Yi, Shiwei Qiu, Huixian Tang, Zongyi Yi, Lu Wang, Zhiwei Lu, Jiangping Xie, Haoyue Liu, Gangbin Tang, Yongjian Zhang, Ying Yu, Pengfei Yuan, Ying Liu, Wei Xiong, Wensheng Wei

Issue&Volume: 2026-06-10

Abstract: Leveraging endogenous adenosine deaminase (ADAR) enzymes through engineered ADAR-recruiting RNAs (arRNAs) offers a safe, programmable strategy for RNA editing without exogenous enzyme delivery. Yet an incomplete understanding of ADAR’s mechanistic basis has hindered the rational design of arRNAs with improved efficiency and precision. Here, we present LEAPER 3.0 (leveraging endogenous ADAR for programmable editing of RNA), a next-generation RNA-editing platform that integrates AlphaFold 3 structural predictions with systematic biochemical and cellular assays to define the molecular interface between ADAR1 or ADAR2 and double-stranded RNA. These insights enabled the rational optimization of arRNAs to expand the editable sequence range to previously refractory sites, suppress bystander editing within duplex regions, and achieve single-nucleotide discrimination among adjacent adenosines. This work elucidates the structural and mechanistic principles underlying arRNA-mediated editing and establishes a framework for the rational design of highly efficient and precise A-to-I RNA-editing tools.

DOI: 10.1016/j.cell.2026.04.047

Source: https://www.cell.com/cell/abstract/S0092-8674(26)00514-3