The future looks brighter after 25 years of retinal gene therapy

The first report of in vivo gene delivery to the retina dates back to 1987 when a retroviral vector was injected intraocularly in newborn mice. Later came the observation that retinal cells could be successfully transduced using adenoviral and, then, adeno-associated and lentiviral vectors. By 2000, it had became clear that the eye, compared with other organs and tissues, provides a number of advantages for in vivo gene therapy with regard to safety, efficacy and route to clinical application. This has prompted the development of many successful proof-of-concept studies in animal models. The demonstration that sight could be restored in a large animal model with a congenital form of blindness was a major landmark that opened the door to the first-in-human trials for recessively inherited blinding conditions. With these first human studies demonstrating safety as well as some efficacy, retinal gene therapy has now come of age. Rapid clinical development has highlighted various new challenges, including the treatment of patients with advanced photoreceptor degeneration or dominantly inherited retinal dystrophies and those with defects in large genes, yet given the progress over the last 25 years, we expect a bright future for retinal gene therapy.