CRISPR/Cas9基因编辑技术在构建眼科疾病动物模型中的应用  

Application of CRISPR/Cas9 gene editing technology in the construction of animal models of ophthalmic diseases

作　　者：马啸辰(综述) 刘红玲(审校)[1] Ma Xiaochen;Liu Hongling(Department of Ophthalmology,First Affiliate Hospital of Harbin Medical University,Harbin 150001,China)

机构地区：[1]哈尔滨医科大学第一附属医院眼科医院,哈尔滨150001

出　　处：《中华实验眼科杂志》2022年第10期972-975,共4页Chinese Journal Of Experimental Ophthalmology

基　　金：国家自然科学基金项目(81301325);中国初级卫生保健基金会眼科新技术孵化基金项目(FB2022008629)。

摘　　要：成簇规律间隔短回文重复序列及其相关蛋白9(CRISPR/Cas9)系统是一种利用RNA指导核酸内切酶进行基因编辑的技术,具有操作简便、靶向精准、周期短、基因敲除效率高等特点,被广泛用于多个物种的基因编辑及疾病基因治疗中。目前,采用该技术已构建了多种眼科疾病动物模型,如角膜营养不良模型(UBIAD1、TGF-βR124C基因突变)、青光眼模型(MYOC Y435H、OPTN E50K和PMEL基因突变)、白内障模型(GJA8、KPNA4、c-Maf、AQP5和PIKFYVE基因突变)、Leber先天性黑矇动物模型(KCNJ13和LCA5基因突变)、视网膜母细胞瘤动物模型(RB1/RBL基因突变)和视网膜色素变性动物模型(HKDC1、C8ORF37、CERKL、PRCD、ASRGL1、LRAT和PDE6B基因突变)等。还有研究者采用该基因编辑技术进一步证实了MFRP、CPAMD8、Pax6和FREM基因在动物眼部发育过程中的作用。本文就CRISPR/Cas9基因编辑技术在构建眼科疾病动物模型中的应用进行综述。The clustered regularly interspaced short palindromic repeat(CRISPR)/CRISPR-associated endonuclease 9(Cas9)technology is a gene editing technology that uses RNA to guide endonucleases.This technology is rapidly used in gene editing and disease gene therapy in multiple species because of its easy operation,precise targeting,short cycle,and high gene knockout efficiency.At present,the corneal dystrophy model(UBIAD1,TGF-βR124C gene mutations),glaucoma model(MYOC Y435H,OPTN E50K and PMEL gene mutations),cataract model(GJA8,KPNA4,C-MAF,AQP5 and PIKFYVE gene mutations),Leber congenital amaurosis animal model(KCNJ13 and LCA5 gene mutations),retinblastoma animal model(RB1/RBL gene mutations)and retinitis pigmentosa models(HKDC1,C8ORF37,CERKL,PRCD,ASRGL1,LRAT and PDE6B gene mutations)have been constructed by using this technology.The role of MFRP,CPAMD8,Pax6,and FREM genes in animal eye development has been further confirmed via this technology.The application of CRISPR/Cas9 gene editing technology in the construction of animal models of ophthalmic diseases was reviewed in this article.

关 键 词：CRISPR-Cas系统 基因编辑 眼病 动物模型 

分 类 号：R77[医药卫生—眼科] R-332[医药卫生—临床医学]