基于CRISPR/Cas9的基因编辑技术在遗传性视网膜疾病治疗中的研究进展

The progress of the gene editing therapy of inherited retinal diseases based onCRISPR/Cas9

遗传性视网膜疾病(IRD)是临床上难治性致盲眼病,基因替代疗法在IRD的治疗中已经取得了初步的进展。对于难以通过基因替代疗法进行治疗的IRD,基因编辑技术提供了一种新的治疗思路。针对IRD不同的遗传模式和致病变异类型,可以通过破坏致病变异基因配合或不配合野生型基因的补充治疗、精确修复致病变异基因等策略以达到治疗疾病的目的。CRISPR/Cas9基因编辑技术及以此为基础的碱基编辑技术和先导编辑技术在视网膜色素变性、Usher综合征、Leber先天性黑矇、锥杆细胞营养不良等疾病动物模型体内实现了致病变异基因的编辑,在IRD的基因编辑治疗中展现了良好的应用前景。

Inherited retinal diseases(IRDs)are the major cause of refractory blinding eye diseases,and gene replacement therapy has already made preliminary progress in the treatment of IRDs.For IRDs that cannot be treated by gene replacement therapy,gene editing provides an alternative therapeutic method.Strategies like disruption of pathogenic variants with or without gene augmentation therapy and precise repair of pathogenic variants can be applied for IRDs with various inheritance patterns and pathogenic variants.In animal models of retinitis pigmentosa,Usher syndrome,Leber congenital amaurosis,cone rod cell dystrophy,and other disorders,CRISPR/Cas9,base editing,and prime editing showed the potential to edit pathogenic variations in vivo,indicating a promising future for gene editing therapy of IRDs.