Prime Editing Strategy to Install the RPE65 c.1430A>G Dominant Mutation

The retinal pigment epithelium 65-kDa protein (RPE65) is a retinal isomerase that is an essential component of the visual cycle. Mutations in RPE65 are typically associated with autosomal recessive retinitis pigmentosa and Leber congenital amaurosis. Here, we report on a patient with RPE65-mediated autosomal dominant retinitis pigmentosa (adRP) who has widespread chorioretinal atrophy with significant macular involvement and only small areas of retinal preservation. In future studies, we plan to model the pathobiology of RPE65-mediated adRP using induced pluripotent stem cell (iPSC)-derived RPE. To effectively model rare mutations using iPSC-derived RPE and screen gene editing correction approaches, we require a strategy to install the desired mutation in wild-type iPSC and HEK293T. In this study, we developed a prime editing strategy for the installation of the pathogenic RPE65 c.1430A>G mutation underlying our patient's disease.