视网膜色素变性（RP）是主要的遗传性致盲病之一，目前尚缺乏有效的治疗手段。视紫红质（RHO）基因突变是导致RP最常见的病因，以第23位脯氨酸突变为组氨酸（P23H）最为常见。P23H 导致的进行性光感受器细胞和色素上皮细胞死亡，主要为RHO基因的功能获得性突变和显负性突变所导致，单纯地导入正常基因的并不能达到治疗的目的。 “抑制和替换”的治疗方式（先使用一定的技术手段抑制或者剔除功能获得性突变和显负性突变的产物，然后再补充功能正常的基因进行治疗），或者使用基因编辑手段直接纠正原突变位点才有望进行有效治疗。因此，本项研究探索使用靶向RHO的CRISPR/Cpf1载体敲除RHO突变体，同时将正常的RHO基因递送至视网膜光感受器细胞内进行RP的基因治疗；或者使用靶向RHO基因P23H突变位点的CRISPR/Cpf1载体载体，同时提供一段与靶点序列同源的供体DNA，对突变位点进行精准的修复。

Retinitis Pigmentosa (RP) is a main cause of genetic inducesed blindness, which still lack of effective treatment. Mutaions on Rhodopsin (RHO) gene is the most common genetic etiology of RP, and the P23H mutation, histidine substituted for proline at position 23, account for the biggest portion of RHO mutation. The progeressive cell degeneration on photoreceptor cells incuded by P23H can be attribute to the Gain-of-function mutation and Dominant-negative mutation effects of this mutaion which can not be treated by simply tranceducing normal RHO gene. However, suppression and substiitution strategy (knocking out the mutated gene and simultaneously supply normal gene), or precisly precisly correcting the muatation sites should acchieve more effective treatment of RP. Here, this study explores the use of CRISPR/Cpf1 system targeting P23H muation combining with delivery of normal RHO gene to retina to treat RHO in vivo.