SBIR Phase I: Preclinical Validation of an Ocular Antioxidant Enhancing Gene Delivery Vehicle to Target Dry Macular Degeneration

The broader impact /commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to develop and commercialize a gene therapy to reverse the effects of dry age-related macular degeneration in over 200 million people worldwide over the age of 50. This therapy may prevent loss of vision and independence by helping people retain their ability to drive, handle finances, see faces of loved ones, and live independently. Not only would this improve the quality of life in patients with macular degeneration, but it would also decrease the economic burden of visual disability on the US healthcare system. The proposed therapy is a durable treatment that can potentially last a lifetime and be delivered into the eye with an in-office procedure. No treatments currently exist for this disease. This technology will meet an unmet need for hundreds of millions of patients with no other treatment options. This Small Business Innovation Research (SBIR) Phase I project seeks to optimize the design and dose required to safely reach the retina with desired expression levels and elicit pan-retinal protection from light-induced retinal degeneration. The proposed AAV-mediated modifier therapy is an epigenetic regulator that modulates gene expression involved in neural stem cell renewal rather than replacing various genes associated with macular degeneration. The proposed SBIR Phase 1 technical plan addresses the various tests for optimization of the delivery capsid, which will deliver an episomal gene that acts as an epigenetic regulator and boosts innate antioxidant genes, reduces cellular senescence, repairs DNA damage, and increases the expression of anti-apoptotic genes in retinal cells. In this SBIR Phase 1 study, we will conduct in vitro (retinal pigment epithelium cells) and in vivo experiments to determine the dosage, safety and efficacy of the treatment for subsequent studies. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.