The pharmacology program established the mechanism of action and biological activity of voretigene neparvovec. The primary pharmacology studies were conducted in animal models of RPE65-mediated retinal dystrophy (rd12 mice and RPE65-mutant dogs). Subretinal injection of voretigene neparvovec led to the expression of hRPE65 protein in retinal pigment epithelial cells. This restored the visual cycle, as demonstrated by the regeneration of 11-cis-retinal, and resulted in improved retinal function (measured by ERG) and restoration of visual behaviors (e.g., navigating a maze) in a dose-dependent manner. These studies provided the essential proof-of-concept for human clinical trials.