While some long-term clinical studies of Luxturna show that visual function gains are sustained up to 4 and 7.5 years (7–9), other RPE65 gene therapy trials report unabated retinal degeneration and relapse in visual acuity a few years after treatment (10–12). Collectively, these limitations underscore the urge to explore alternative strategies to gene supplementation for addressing the broad spectrum of IRDs. This evidence concerns the gene RPE65 and retinal degeneration.