CRISPR/Cas9基因编辑技术在遗传性视网膜疾病中的应用  

Application of CRISPR/Cas9 genome editing technology in hereditary retinal diseases

作　　者：孙玺皓(综述) 唐仕波 陈建苏(审校) Sun Xihao;Tang shibo;Chen Jiansu(Aier School of Ophthalmology,Central South University,Aier Eye Institute Changsha,Chiangsha 410015,China)

机构地区：[1]中南大学爱尔眼科学院爱尔眼科研究所,长沙410015

出　　处：《中华实验眼科杂志》2023年第9期925-930,共6页Chinese Journal Of Experimental Ophthalmology

基　　金：国家自然科学基金项目(32061160469)。

摘　　要：目前,一些遗传性视网膜疾病的突变基因已经得到确认,但仍缺乏有效的治疗方法。成簇规律间隔短回文重复序列(CRISPR)和CRISPR相关蛋白(CAS)系统可以通过非同源末端连接及同源定向修复的方式编辑人类基因组DNA,其为遗传性视网膜疾病的治疗提供了更多的可能性。CRISPR/Cas9不仅可以纠正遗传性疾病患者来源特异性诱导多能干细胞(iPSCs)的突变基因,随后分化为视网膜相关的细胞,进而实施细胞治疗;其也可以通过载体传递至体内,直接作用于靶细胞实现体内基因编辑。CRISPR/Cas9基因编辑技术在遗传性视网膜疾病中的应用主要集中在视网膜色素变性、遗传性X连锁青少年视网膜劈裂症、Leber先天性黑矇10型等疾病中,其中体外应用CRISPR/Cas9治疗LCA10已经进入临床试验阶段。本文对CRISPR/Cas9基因编辑技术的作用机制、研究进展,以及其在遗传性视网膜疾病中的应用进展进行综述。Several mutant genes for inherited retinal diseases have been identified,but effective treatments are still lacking.The clustered regularly interspaced short palindromic repeats(CRISPR)/CRISPR-associated protein(Cas)system can edit human genomic DNA by nonhomologous end joining or homology-directed repair,offering more possibilities for the treatment of hereditary retinal diseases.CRISPR/Cas9 not only can genetically correct patient-derived induced pluripotent stem cells(iPSCs)to observe their differentiation into retinal cells thereby,thereby exploring the pathogenesis of the disease and implementing cell therapy,but can also be delivered to the body via vectors and directly act on target cells to achieve in vivo gene editing.CRISPR/Cas9 gene editing technology in hereditary retinal diseases has been mainly used in retinitis pigmentosa,hereditary X-linked juvenile retinoschisis,and Leber congenital amaurosis 10,of which the in vitro application of CRISPR/Cas9 for Leber congenital amaurosis 10 has entered the clinical trial stage.In this paper,we reviewed the mechanism and key advances of CRISPR/Cas9 and provided an overview of gene editing in IRDs.

关 键 词：基因编辑 CRISPR/Cas9 遗传性视网膜疾病 

分 类 号：R774.1[医药卫生—眼科]