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CRISPR/Cas9基因组编辑技术及其在动物基因组定点修饰中的应用

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  • 1. 四川农业大学动物医学院,成都 611130;
    2. 中国科学院动物研究所,计划生育生殖生物学国家重点实验室,北京 100101
周金伟,硕士,专业方向:大动物遗传与修饰。E-mail: zhoujinwei08@126.com

收稿日期: 2015-02-03

  网络出版日期: 2015-10-20

基金资助

国家自然科学基金项目(编号:31272400,31172379)和四川农业大学学科建设双支计划项目(编号:3570806)资助

CRISPR/Cas9 genome editing technique and its application in site-directed genome modification of animals

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  • 1. College of Veterinary Medicine, Sichuan Agricultural University, Chengdu 611130, China;
    2. State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China

Received date: 2015-02-03

  Online published: 2015-10-20

摘要

CRISPR/Cas系统是细菌和古生菌中抵抗外源病毒或质粒入侵的获得性免疫系统,利用CRISPR RNAs (crRNAs)引导Cas核酸酶沉默入侵的核酸。通过分子生物学改造使Ⅱ型CRISPR/Cas系统成为一种高效的基因组定点修饰技术,并且比锌指核酸酶(Zinc-finger nucleases, ZFNs)和TALE核酸酶(Transcription activator like effector nucleases, TALENs)结构更简单,更容易设计和应用。文章主要介绍了CRISPR/Cas9系统成为高效基因组定点修饰技术的发展历程、Ⅱ型CRISPR/Cas的工作原理和改造过程以及在动物基因组定点修饰的应用,剖析了该技术存在的问题和现有改进方案,并与成功案例相结合展望了CRISPR/Cas9系统的应用前景,以期为动物性状改良和人类疾病动物模型的创立提供新思路。

本文引用格式

周金伟, 徐绮嫔, 姚婧, 余树民, 曹随忠 . CRISPR/Cas9基因组编辑技术及其在动物基因组定点修饰中的应用[J]. 遗传, 2015 , 37(10) : 1011 -1020 . DOI: 10.16288/j.yczz.15-066

Abstract

CRISPR/Cas system, which uses CRISPR RNAs (crRNAs) to guide Cas nuclease to silence invading nucleic acids, is self-defense system against exogenous virus or plasmid in bacteria and archaea. Through molecular modification, the typeⅡCRISPR/Cas system has become a highly efficient site-directed genome editing technique, which is simpler than zinc-finger nucleases (ZFNs) and transcription activator like effector nucleases (TALENs) and easier to be designed and applied. In this review, we summarize the evolutionary history of CRISPR/Cas9 system, the working principle and modification process of type Ⅱ CRISPR/Cas and its application in animal genome modification. We also analyze the existing problems and improvement program of the CRISPR/Cas9 system as well as its application prospect combined with successful cases, which may provide innovative perspectives on improving animal traits and establishing animal models of human diseases.

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