基因编辑治疗视网膜疾病的研究进展

Research progress of gene editing for retinal diseases

成簇规律间隔短回文重复序列(CRISPR)/CRISPR相关核酸酶(Cas)系统和诱导Cas蛋白到达基因组预定区域的RNA基因编辑技术,在视网膜疾病的治疗中具有广大应用前景。迄今为止,已知有200多个基因可通过干扰视锥细胞、视杆细胞或视网膜色素上皮细胞的发育、功能和存活,从而导致遗传性视网膜营养不良(IRD)。CRISPR/Cas系统可以永久性、精确地替代或消除致病基因突变,治疗包括视网膜色素变性和Leber先天性黑矇等多种IRD。不仅如此,多因素相关的年龄相关性黄斑病变也被证实可通过CRISPR/Cas系统得到治疗缓解。本文主要论述CRISPR/Cas系统的作用机制以及该项基因编辑技术在视网膜疾病中的应用前景。

The genome editing technology based on clustered regularly interspaced short palindromic repeat(CRISPR)/associated protein(Cas)and an RNA that guides the Cas protein to a predetermined region of the genome has broad prospects in the treatment of retinal diseases(RDs).To date,more than 200 genes have been known to cause inherited retinal dystrophies(IRDs),which perturb the development,function and survival of rod and cone photoreceptors or retinal pigment epithelial cells.CRISPR/Cas system can permanently and precisely replace or remove genetic mutations causative of a disease,and treat a variety of diseases including retinitis pigmentosa and Leber’s congenital amaurosis(LCA).Moreover,multifactorial forms,for example,age-related macular degeneration(AMD)has also been proved to be treatable with the CRISPR/Cas system.In this review,we will introduce the mechanism of CRISPR/Cas system,then we will focus on applications of CRISPR/Cas genome editing in the retina.