The nonclinical program for voretigene neparvovec was designed to establish proof-of-concept, determine a safe starting dose, and characterize the toxicology profile. The program demonstrated the expected biological activity and a favorable safety profile supporting clinical development. In vivo studies in RPE65-mutant dog and mouse models established proof-of-concept, demonstrating dose-dependent RPE65 protein expression and restoration of visual function. Toxicology studies in dogs and non-human primates (NHPs) confirmed that subretinal administration of voretigene neparvovec is well-tolerated with only mild, transient ocular inflammation observed, consistent with the surgical procedure. No standard carcinogenicity, genotoxicity, or reproductive toxicology studies were conducted, consistent with regulatory guidance for gene therapy products of this nature.