RNA碱基编辑及其在疾病治疗中的研究进展  

Progress of research on RNA base editing toward therapeutic

作　　者：黄强 罗楠 庄元 彭金英 伊成器 HUANG Qiang;LUO Nan;ZHUANG Yuan;PENG JinYing;YI ChengQi(State Key Laboratory of Protein and Plant Gene Research,School of Life Sciences,Peking University,Beijing 100871,China;Peking-Tsinghua Center for Life Sciences,Peking University,Beijing 100871,China;Department of Chemical Biology and Synthetic and Functional Biomolecules Center,College of Chemistry and Molecular Engineering,Peking University,Beijing 100871,China;Beijjing Advanced Center of RNA Biology(BEACON),Beijing 100871,China)

机构地区：[1]北京大学生命科学学院,蛋白质与植物基因研究国家重点实验室,北京100871 [2]北京大学,北大-清华生命科学联合中心,北京100871 [3]北京大学化学与分子工程学院化学生物系及合成与功能生物分子研究中心,北京100871 [4]核糖核酸北京研究中心,北京100871

出　　处：《中国科学：生命科学》2024年第4期586-601,共16页Scientia Sinica(Vitae)

基　　金：中国农村农业部(批准号:NK2022010102);北京市科学技术委员会基金(批准号:Z231100002723005);国家自然科学基金(批准号:32200467,21825701);中国博士后科学基金(批准号:2022M710222)资助。

摘　　要：基于CRISPR的碱基编辑器是生物学研究的强大工具,并为遗传病的治疗带来新的希望.然而,DNA碱基编辑器的潜在脱靶效应却带来了治疗上的风险.相比之下,RNA水平的碱基编辑具有相对灵活、可逆且风险较低的特点,并在纠正疾病相关点突变方面取得了重大进展,对生物学基础研究和治疗学的发展产生了深远的影响.本文总结了新兴的基于A-to-I、C-to-U、假尿嘧啶修饰等的RNA碱基编辑器,全面概述了其设计、效率和在疾病治疗中的应用.最后,本文深入讨论了RNA碱基编辑在疾病治疗上的局限性和可能的发展方向,以期对RNA基因编辑实践提供理论参考.CRISPR-based base editors are powerful tools for biological research and has given promise for the treatment of genetic diseases.However,undesired off-target editing is also permanent,which poses considerable risks for therapeutics.Alternatively,RNA base editing also corrects disease-causing mutations and is relatively flexible,reversible,and does not lead to potentially persistent genotoxic effects.In recent years,RNA base editing has made significant progress in correcting disease-associated point mutations.These breakthroughs have had a profound impact on the development of biotechnology,biomedical research and therapeutics.In this paper,we summarize emerging RNA editors based on A-to-I,C-to-U,pseudouridylation,etc.We provide a comprehensive overview of the design and performance of contemporary RNA base editors,while highlighting the latest breakthroughs and their application in disease-related settings.Finally,we compare different editing tools and discuss the limitations and opportunities RNA base editing for therapeutic purposes.

关 键 词：RNA编辑 靶向修饰 碱基编辑 脱靶 脱氨 遗传病治疗 

分 类 号：R45[医药卫生—治疗学]