CRISPR/Cas9技术在遗传性眼病基因治疗中的应用  

Applications of CRISPR/Cas9 genome editing technology in gene therapy for hereditary eye diseases

作　　者：吴世靖(综述) 睢瑞芳(审校)[1] Wu Shijing;Sui Ruifang(Department of Ophthalmology,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China)

机构地区：[1]中国医学科学院,北京协和医学院,北京协和医院眼科,北京100730

出　　处：《中华实验眼科杂志》2018年第11期892-896,共5页Chinese Journal Of Experimental Ophthalmology

基　　金：中国医学科学院医学与健康科技创新工程经费资助项目(2016-I2M-1-002)。

摘　　要：成簇规律间隔短回文重复序列(CRISPR)/CRISPR相关核酸酶(Cas)系统是一种存在于细菌和古菌内抵抗外源病毒和质粒侵袭的适应性免疫系统,自其发现的30余年来,研究者对其在生物体内免疫过程和利用其进行基因编辑的作用机制的认识不断深入。研究发现,由Ⅱ型CRISPR/Cas改造而来的CRISPR/Cas9系统准确和有效地进行基因编辑。近年来,随着基因测序技术的进步和发展,多种眼科遗传病的致病基因诊断更加明确,同时随着在真核细胞里Cas9作用特异性的提高,基因编辑技术在遗传性眼病的诊疗方面正展现出巨大的潜力。目前,CRISPR/Cas9基因编辑技术在眼科的应用已扩展到先天性白内障、先天性青光眼、视网膜色素变性(RP)、先天性角膜营养不良、Leber先天性黑矇(LCA)和Usher综合征等遗传性眼病的基因治疗。此外,CRISPR/Cas9基因编辑技术与腺相关病毒载体(AAV)和诱导性多能干细胞(iPSCs)研究的结合为遗传性疾病的治疗提供了更多的可能性和新的途径。本文就CRISPR/Cas9基因编辑技术的机制以及该技术在眼遗传病基因治疗方面中的应用进行综述。Clustered regulatory interspaced short palindromic repeat(CRISPR)/CRISPR associated nuclease(Cas)system is an adaptive immune system that confers resistance to exogenous virus or plasmid in bacteria and archaea,over the 30 years since its discovery,researchers have a better understanding of its immune processes in vivo and the mechanisms of gene editing by using its function.Researches found that CRISPR/Cas9 system modified from typeⅡCRISPR/Cas may edit genome accurately and effectively.In recent years,with the progress and development of gene sequencing technology,it is more explicit to make genetic diagnosis of a variety of hereditary eye diseases,and with the improvement of specificity for Cas9 in eukaryotic cells,gene editing is showing a great potential in the field of treating hereditary eye diseases.At present,the application of CRISPR/Cas9 gene editing technology has extended to the gene therapy of some hereditary eye diseases,such as congenital cataract,congenital glaucoma,retinitis pigmentosa(RP),congenital corneal dystrophy,Leber congenital amaurosis(LCA)and Usher syndrome.Besides,the combination of CRISPR/Cas9 gene editing technology with adeno-associated virus vectors(AAV)and induced pluripotent stem cells(iPSCs)research offers more possibilities and new approaches for the treatment of hereditary diseases.This article reviewed the mechanism of CRISPR/Cas9 and its applications in gene therapy for hereditary eye diseases.

关 键 词：成簇规律间隔短回文重复序列 CRISPR-Cas系统 基因治疗 眼遗传疾病 

分 类 号：R473.77[医药卫生—护理学]