环状RNA:从生物发生到医学治疗  

CircRNAs:from Biogenesis to Therapeutic Application

作　　者：蒋凯 周蓉 曾晶 高璐 JIANG Kai;ZHOU Rong;ZENG Jing;GAO Lu(Therorna Inc.,Beijing 10056,China,Beijing 100056,China)

机构地区：[1]园因(北京)生物科技有限公司,北京100056

出　　处：《中国医药导刊》2023年第1期21-27,共7页Chinese Journal of Medicinal Guide

摘　　要：环状RNA(CircRNAs)是一类单链共价闭环RNA,在真核细胞中由反向剪接形成。CircRNAs作为microRNA海绵,蛋白海绵,转录和翻译调节因子,在各种疾病相关的信号传导通路中发挥着重要作用。类似于mRNA和siRNA,CircRNAs作为现代医学新疗法的潜力已经被广泛探索。最近,尤其是在应对新冠肺炎疫情,mRNA疫苗的安全性和预防严重症状的有效性已被证实。但是,mRNA相对短的半衰期限制了其在更广泛的治疗领域当中的应用。相对而言,CircRNAs缺乏外切核酸酶介导的降解所需的游离端,因而显示出更强的体内持久性。此外,溴化氰化学法、RNA或者DNA连接酶法、以及自剪切内含子的核酶法,都可能被优化成为高度有效的体外环化方法。CircRNAs因其生物功能的重要性和技术可行性,正在成为一种极具潜力的治疗方法。本研究将系统阐述CircRNAs生物发生、生物学功能、体外环化及潜在的应用,以期为进一步研究CircRNAs提供借鉴。Circular RNAs(CircRNAs)are a class of single-stranded covalently closed RNAs derived from back-splicing in eukaryotic cells.CircRNAs play important roles in a variety of disease related signaling pathways as microRNA sponges,protein sponges,transcriptional regulators,and translational regulators.Similar as mRNA and siRNA,the potential of circRNAs as a novel modality of novel medicine has been explored.Recently,mRNA vaccines have been proving safe and effective in preventing serious conditions,especially during the COVID-19 pandemic.However,the relatively short half-life of mRNAs remains as hurdle for their broader therapeutic applications.In the other hand,circRNAs have demonstrated much improved durability in vivo due to lack of free ends necessary for exonuclease-mediated degradation.In addition,several RNA circularization methods,including chemical ligation,enzymatic ligation,and ribozymatic ligation,have been optimized to be highly effective in vitro.Taking together,circRNAs could become a promising therapeutic approach based on important biological functions and technical feasibility.In this study,the biogenesis,biological functions,in vitro cyclization and potential applications of CircRNAs will be reviewed in order to provide reference for further study of CircRNAs.

关 键 词：环状RNAs 反向剪接 内部核糖体进入位点 体外环化 RNA疗法 

分 类 号：Q522[生物学—生物化学]