大中型动物基因敲除技术的研究进展  

The Development of Gene Knockout Technologies in Large and Medium Animal Models

作　　者：刘雪静[1] 王欢[1] 严放[1] 高明明[1] 刘国庆[1] 黄薇[1] 

机构地区：[1]北京大学医学部心血管研究所,北京100191

出　　处：《生理科学进展》2015年第1期11-16,共6页Progress in Physiological Sciences

基　　金：国家自然科学基金(81070242)资助课题

摘　　要：基因敲除是20世纪80年代末发展起来的一门新技术,2007年获得诺贝尔生理或医学奖。然而在很长一段时间内,由于胚胎干细胞(embryonic stem cell,ES cell)体外的成功培养仅限于小鼠,该技术很难在其它动物种系中完成。2008年至今随着新ES细胞基因打靶、锌指核酸酶(zinc finger nucleases,ZFNs)、转录激活因子样效应物核酸酶(transcription activator-like effect nucleases,TALENs)和规律成簇的间隔短回文重复序列/Cas9内切酶(clusters of regularly interspased short palindromic repeats/Cas9,CRISPR/Cas9)等新技术的不断涌现,使在疾病研究中更接近于人类的大中型动物基因敲除成为可能。本综述将介绍近几年来以上几种基因敲除新技术在大中型动物上的成功应用及重大意义。Technique of homologous recombination based gene targeting developed in the late 1980 s and won the Nobel Prize in Physiology or Medicine in 2007. However,this technique could only performed in mice which embryonic stem（ ES） cells could keep in the potential of multifunction in vitro. Therefore gene knockout technology was difficult to be applied in other species of animals for a long time. Since 2008,with the development of the new technologies,such as the new ES cell gene targeting,zinc finger nucleases（ ZFNs）,transcription activator-like effector nucleases（ TALENs） and clusters of regularly interspaced short palindromic repeats / Cas9（ CRISPR / Cas9）,building gene knockout in large and medium animals models which are similar to human in disease research becomes possible. This review describes some new gene knockout technologies in large and medium animal models for recent years.

关 键 词：基因敲除 ES细胞基因打靶 ZFNs TALENs CRISPR/Cas9 大中型动物模型 

分 类 号：R394[医药卫生—医学遗传学] Q819[医药卫生—基础医学]