Generation of nonhuman primate retinitis pigmentosa model by in situ knockout of RHO in rhesus macaque retina
Posted 31 Jul 2020
bioRxiv DOI: 10.1101/2020.07.29.226787 (published DOI: 10.1016/j.scib.2020.09.008)
Posted 31 Jul 2020
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 (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. ### Competing Interest Statement T.X., M.Z. and S.L. are inventors on a pending patent related to this work filed by the University of Science and Technology of China (No. 202010685517.4 and No.202010685115.4, filed on July 16th 2019). The authors declare no other competing interests.
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