Retinitis pigmentosa (RP) is a form of inherited retinal degenerative diseases that ultimately involves the macula, which is present in primates but not in the rodents. Therefore, creating nonhuman primate (NHP) models of RP is of critical importance to study its mechanism of pathogenesis and to evaluate potential therapeutic options in the future. Here we applied adeno-associated virus (AAV)-delivered CRISPR/SaCas9 technology to knockout the RHO gene in the retinae of the adult rhesus macaque (Macaca mulatta) to investigate the hypothesis whether non-germline mutation of the RHO gene is sufficient to recapitulate RP. Through a series of studies, we were able to demonstrate successful somatic editing of the RHO gene and reduced RHO protein expression. More importantly, the mutant macaque retinae displayed clinical RP phenotypes, including photoreceptor degeneration, retinal thinning, abnormal rod subcellular structures, and reduced photoresponse. Therefore, we suggest somatic editing of the RHO gene is able to phenocopy RP, and the reduced time span in generating NHP mutant accelerates RP research and expands the utility of NHP model for human disease study.

视网膜色素变性 (RP) 是一种遗传性视网膜退行性疾病，最终累及黄斑，黄斑存在于灵长类动物中，但不存在于啮齿动物中。因此，创建 RP 的非人灵长类动物 (NHP) 模型对于研究其发病机制和评估未来潜在的治疗选择至关重要。在这里，我们应用腺相关病毒 (AAV) 传递的 CRISPR/SaCas9 技术敲除成年恒河猴 ( Macaca mulatta ) 视网膜中的RHO基因，以研究RHO基因的非胚系突变是否足以重演的假设回波。通过一系列研究，我们能够证明RHO的成功体细胞编辑基因和减少的 RHO 蛋白表达。更重要的是，突变的猕猴视网膜表现出临床 RP 表型，包括光感受器退化、视网膜变薄、视杆亚细胞结构异常和光响应降低。因此，我们建议对RHO基因进行体细胞编辑能够对 RP 进行表型复制，并且减少生成 NHP 突变体的时间跨度可以加速 RP 研究并扩大 NHP 模型在人类疾病研究中的实用性。