Generation of nonhuman primate retinitis pigmentosa model by in situ knockout of RHO in rhesus macaque retina [article]

Shouzhen Li, Yingzhou Hu, Yunqin Li, Min Hu, Wenchao Wang, Yuqian Ma, Yuan Cai, Min Wei, Yichuan Yao, Yun Wang, Kai Dong, Yonghao Gu (+6 others)
2020 bioRxiv   pre-print
Retinitis pigmentosa (RP) is a form of inherited retinal degenerative disease 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
more » ... lt 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.
doi:10.1101/2020.07.29.226787 fatcat:mgil5wykm5cfxhsu4td7mxebgm