摘要
RNA干扰(RNA interference,RNAi)是由双链小RNA(small interfering RNA,siRNA)介导的转录后靶基因沉默现象。由于RNAi几乎能够调控所有真核细胞内mRNA的稳定性,因此在基因功能研究和疾病治疗领域都获得了广泛应用。从2018年第一款RNAi药物patisiran获批上市到2024年的7年时间里,已有6款RNAi药物成功上市,且有近百款RNAi药物正处于临床试验阶段,开启了该领域的新纪元。但目前基于RNAi的治疗性药物开发依然面临包括安全性和有效性在内的多种挑战。本文将结合RNAi药物发展历程中的挑战和机遇,讨论RNAi药物的结构、序列、修饰和递送等关键科学问题,总结RNAi药物开发中需要关注的基本规律和准则,探讨RNAi药物未来的发展方向。
RNA interference(RNAi)is an evolutionarily conserved phenomenon of post-transcriptional gene silencing,triggered by perfect complementary small interfering RNA(siRNA)within eukaryotic cells.Since 2018,the U.S.FDA has approved six RNAi drugs,with many others currently under clinical trials,ushering in new era in this field.However,the development of RNAi-based therapeutic drugs faces numerous challenges,including issues of safety and efficacy.In this review,we will examine the challenges and opportunities in the development of RNAi drugs,focusing on key scientific issues,such as structure,sequence,modification,and delivery.Additionally,we will discuss the fundamental principles and guidelines for RNAi drug development and explore future directions in this field.
作者
张宏道
高世琦
吴立刚
ZHANG Hongdao;GAO Shiqi;WU Ligang(Key Laboratory of RNA Science and Engineering,Shanghai Institute of Biochemistry and Cell Biology,Center for Excellence in Molecular Cell Science,Chinese Academy of Sciences,University of Chinese Academy of Sciences,Shanghai 200031,China)
出处
《生命的化学》
CAS
2024年第9期1714-1727,共14页
Chemistry of Life
基金
国家重点研发计划项目(2022YFA1303300)。
