摘要
近年来,基因编辑新技术CRISPR/Cas9(clustered regularly interspaced short palindromic repeats/associated nuclease 9)颇受关注,可用于在体内或体外编辑多种细胞中的单个或多个基因,为基因功能研究提供了新思路。Cas9核酸酶可以通过改变其引导的单一向导RNA(single-guideRNA,sgRNA)序列,结合到新的特定基因序列进行靶向编辑。研究发现,CRISPR/Cas9系统存在的脱靶风险已成为该技术实际应用过程中的一个挑战。本文对CRISPR/Cas9系统作用机制、肿瘤临床应用进行简要综述,重点关注该系统存在的脱靶效应,并总结归纳减少或避免脱靶的方法,以期为相关领域研究提供参考。
In recent years,CRISPR/cas9(clustered regularly interspaced short palindromic repeats/associated nuclease 9),a novel gene editing technology,has gained considerable attention and can be utilized to edit single or multiple genes in a variety of cells in vivo or in vitro,which provides a new way for the study of gene function.Currently,CRISPR/Cas9-based gene editing technology is widely used in frontier medical fields such as tumour therapy,providing new and specific treatments for patients who are intolerant to radiotherapy and chemotherapy or are already in advanced stages of malignancy.The Cas9 nuclease can be targeted by altering its single-guide RNA(sgRNA)sequence to bind to a specific new gene sequence.It has been found that the CRISPR/Cas9 system is at risk of off-targeting,that is,the specific sgRNAs can form mismatches with non-target DNA sequences,resulting in unintended mutations at the gene locus,which has become a challenge in the practical application of this technology.This review gives an overview of the mechanism of CRISPR/Cas9 system and the clinical application in tumor treatment with a focus on the off-target effects,and summarizes the ways to reduce or avoid off-target effects,in order to provide reference for researchers in related fields.
作者
于宗菲
翁丽涵
孙诚诚
曹晓钰
叶振
YU Zong-fei;WENG Li-han;SUN Cheng-cheng;CAO Xiao-yu;YE Zhen(Central Laboratory,The Second Affiliated Hospital of Shandong First Medical University&Shandong Academy of Medical Sciences,Tai’an,Shandong Province 271000;College of Clinical and Basic Medicine,Shandong First Medical University&Shandong Academy of Medical Sciences,Jinan,Shandong Province 250117)
出处
《山东第一医科大学（山东省医学科学院）学报》
CAS
2023年第1期74-80,共7页
Journal of Shandong First Medical University ＆ Shandong Academy of Medical Sciences
基金
山东省医药卫生科技发展计划(202011000331)
2022年本科生研究计划(SRTP)暨大学生创新创业训练计划(2022104391109)。
