CRISPR-Cas9技术在医药领域中的应用

CRISPR-Cas9 and its application in medical field

CRISPR-Cas9是存在于细菌和古细菌中的一种抵御噬菌体或质粒侵染的获得性免疫防御系统,它由成簇规律间隔短回文重复基因序列(clustered regularly interspaced short palindromic repeats,CRISPR)和Cas(CRISPR-associated)蛋白组成。天然的II型CRISPR系统已经被改造成第三代基因编辑工具,将单链向导RNA(single-guide RNA,sgRNA)和作为DNA内切酶的Cas9蛋白导入细胞内,即可在基因组特定位置上进行基因编辑。由于CRISPR-Cas9具有简便高效、脱靶效应低等特点,目前已被广泛应用在动物、植物、微生物的生理和病理研究以及药物研发等领域。本文着重讲述了CRISPR-Cas9的作用机制以及它在医药领域中的应用,包括构建生物模型、疾病治疗、药物靶点筛选和CRISPR与免疫疗法的联合应用。

CRISPR-Cas9 system,consisting of clustered regularly interspaced short palindromic repeats(CRISPR)and CRISPR-associated(Cas)proteins,is an acquired immune system that confers resistance to foreign genetic elements such as plasmids and phages.The natural type II CRISPR system has been transformed into a third-generation gene editing tool,which can conduct gene editing at specific positions in the genome by introducing single-strand guide RNA(sgRNA)and Cas9 protein as DNA endonuctase into cells.Due to its characteristics of simplicity,efficiency and relatively low off-target effect,CRISPR-Cas9 has been widely used in the physiological and pathological research of animals,plants and microorganisms as well as drug′s research and development.This review focuses on the mechanism of CRISPR-Cas9 and its application in the medical field,including the construction of biological models,disease treatment,drug target screening and its combination with immunotherapy.