CRISPR/Cas9系统诱导DNA断裂的修复机制研究进展  

Research Progress on Repair Mechanism of DNA Breakage Induced by CRISPR/Cas9 System

作　　者：杨丽芸 陈丽娇 李善刚 YANG Liyun;CHEN Lijiao;LI Shangang(Institute of Primate Translational Medicine,State Key Laboratory of Primate Biomedical Research,Kunming University of Science and Technology,Yunnan Key Laboratory of Primate Biomedical Research,Kunming 650500,China)

机构地区：[1]昆明理工大学灵长类转化医学研究院,省部共建非人灵长类生物医学国家重点实验室,云南中科灵长类生物医学重点实验室,昆明650500

出　　处：《中国细胞生物学学报》2022年第3期500-511,共12页Chinese Journal of Cell Biology

基　　金：国家自然科学基金(批准号:31960215)资助的课题。

摘　　要：近年来,聚类规则间隔的短回文重复序列(clustered regularly interspaced short palindromic repeats,CRISPR)及其相关蛋白(CRISPR-associated protein 9,Cas9)介导的基因编辑技术已广泛应用在生物学、基础医学等研究领域中,通过该技术构建的动物疾病模型推动了对发病机制的探索和基因治疗等方面的研究进展。Cas9核酸酶切割与随后的同源重组(HDR)或非同源末端连接(NHEJ)共同完成基因编辑工作,但是HDR发生的效率较低限制了其应用。因此对NHEJ和HDR修复方式的机制研究对于提高基因编辑的精准性及高效性十分重要。该文主要对CRISPR/Cas9系统应用过程中NHEJ和HDR修复系统的发生机制进行总结并结合相关研究进展进行了展望,为高效利用CRISPR/Cas9技术的研究提供了思路。In recent years,CRISPR (clustered regularly interspaced short palindromic repeats) and its associated protein Cas9 mediated gene editing technology has been widely used in biology,basic medicine and other research fields.The animal disease model constructed by this technology has promoted the research progress of pathogenesis and gene therapy.Cas9 nuclease cleavage and subsequent HDR (homology-directed repair) or NHEJ (non-homologous end joining) achieved gene editing work together,but the low efficiency of HDR restricted its application.Therefore,the mechanism of NHEJ and HDR repair is very important to improve the accuracy and efficiency of gene editing.This review summarizes the mechanism of NHEJ and HDR repair system in the application of CRISPR/Cas9 system,and prospects the related research progress,in order to provide some ideas for the efficient use of CRISPR/Cas9 technology.

关 键 词：CRISPR/Cas9 DSB 同源重组 非同源末端连接 疾病模型 基因治疗 

分 类 号：Q78[生物学—分子生物学]