CRISPR/Cas9技术及其在药物研发中的应用  

CRISPR/Cas9 and its application in drugs development

作　　者：陆娣 李莉[1] 邓贤明[1] 

机构地区：[1]厦门大学生命科学学院,天然产物源靶向药物国家地方联合工程实验室,福建厦门361102

出　　处：《药学学报》2018年第1期11-20,共10页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目(81422045,81603131)

摘　　要：CRISPR/Cas9系统是在细菌和古细菌中发现的一种为抵御病毒和质粒的不断攻击而演化来的获得性免疫防御机制,由规律成簇的间隔短回文重复(clustered regularly interspaced short palindromic repeats,CRISPR)和Cas(CRISPR-associated)蛋白组成。通过改造最简单的II型CRISPR系统,将特殊小向导RNA(small guide RNA,sg RNA)和Cas9核酸内切酶导入细胞内,即可在双链DNA特定位置上进行切割并实现基因敲除或敲入。CRISPR/Cas9系统因其高效基因编辑功能,已被应用于多种生物和多项科研领域。本文综合论述了CRISPR/Cas9技术在药物研发中的应用,如功能基因的筛选和定点编辑、药物靶点筛选和验证、动物模型构建和遗传疾病治疗等,总结了CRISPR/Cas9技术目前所存在的缺陷与改善的方向。CRISPR/Cas9 system, consisting of clustered regularly interspaced short palindromic repeats（CRISPR） and CRISPR-associated（Cas） proteins, is a prokaryotic immune system that confers resistance to foreign genetic elements such as those present within plasmids and phages. A simple version of the CRISPR/Cas system, type II CRISPR, has been modified to edit genomes. By delivering the Cas9 nuclease together with a synthetic guide RNA（sg RNA） into cells, genome can be edited at desired loci site. CRISPR/Cas genome editing techniques have been widely implemented in various species and research areas. In this review, we summarize the several applications of CRISPR/Cas9 in the field of drug discovery and development, which include target gene screening and editing, drug target screening and validation, generation of animal models and treatment of genetic disease, etc. The defects and improvements of CRISPR/Cas9 technology is discussed as well.

关 键 词：CRISPR/Cas9系统 基因组编辑 耐药性突变 靶点验证 药物研发 

分 类 号：R915[医药卫生—微生物与生化药学]