Henan Eye Hospital, Henan Eye Institution, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, 450003, Henan, China.
Eye (Lond). 2023 Mar;37(4):607-617. doi: 10.1038/s41433-022-02169-1. Epub 2022 Aug 1.
The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated nuclease (Cas) system is an adaptive immune defence system that has gradually evolved in bacteria and archaea to combat invading viruses and exogenous DNA. Advances in technology have enabled researchers to enhance their understanding of the immune process in vivo and its potential for use in genome editing. Thus far, applications of CRISPR/Cas9 genome editing technology in ophthalmology have included gene therapy for corneal dystrophy, glaucoma, congenital cataract, Leber's congenital amaurosis, retinitis pigmentosa, Usher syndrome, fundus neovascular disease, proliferative vitreoretinopathy, retinoblastoma and other eye diseases. Additionally, the combination of CRISPR/Cas9 genome editing technology with adeno-associated virus vector and inducible pluripotent stem cells provides further therapeutic avenues for the treatment of eye diseases. Nonetheless, many challenges remain in the development of clinically feasible retinal genome editing therapy. This review discusses the development, as well as mechanism of CRISPR/Cas9 and its applications and challenges in gene therapy for eye diseases.
簇状规律间隔短回文重复序列 (CRISPR)/CRISPR 相关核酸酶 (Cas) 系统是一种适应性免疫防御系统,在细菌和古菌中逐渐进化,以抵御入侵的病毒和外源 DNA。技术的进步使研究人员能够增强对体内免疫过程及其在基因组编辑中应用的理解。迄今为止,CRISPR/Cas9 基因组编辑技术在眼科学中的应用包括角膜营养不良、青光眼、先天性白内障、Leber 先天性黑矇、色素性视网膜炎、Usher 综合征、眼底新生血管疾病、增殖性玻璃体视网膜病变、视网膜母细胞瘤和其他眼部疾病的基因治疗。此外,CRISPR/Cas9 基因组编辑技术与腺相关病毒载体和诱导多能干细胞的结合为眼部疾病的治疗提供了进一步的治疗途径。尽管如此,在开发临床可行的视网膜基因组编辑治疗方面仍存在许多挑战。本文讨论了 CRISPR/Cas9 的发展及其机制,以及其在眼部疾病基因治疗中的应用和挑战。