RPE65 and Leber congenital amaurosis: Although the mechanism by which RPE65 deficiency causes early cone degeneration is still unclear,19 we demonstrated that restoring RPE65 expression using PE-based gene editing can enhance retinal and visual function, restore cone morphology and slow cone loss, as described in RPE65 gene replacement therapies.17,19,31 A gene replacement therapy, voretigene neparvovec-rzyl (Luxturna), has already been approved by the U.S. Food and Drug Administration (FDA) for treating patients with biallelic RPE65 mutation-associated LCA.