Retinal gene therapies for inherited ocular diseases: Translational delivery strategies from bench to bedside

Inherited retinal diseases (IRDs), including retinitis pigmentosa, Leber congenital amaurosis, and Stargardt disease, represent a major cause of inherited visual impairment and blindness, particularly in working-age populations. These disorders are genetically heterogeneous and result in progressive degeneration of photoreceptors and the retinal pigment epithelium. The eye offers a uniquely favorable environment for gene therapy due to its anatomical compartmentalization, accessibility, and relative immune privilege; however, successful clinical translation remains constrained by multiple biological and technological barriers. In this review, we adopt a comparative, delivery-centric framework to analyze how different gene delivery strategies navigate key translational challenges, including the blood-retinal barrier, vector tropism, immune responses, payload size limitations, re-dosing feasibility, and manufacturing cost. We systematically contrast viral and non-viral platforms, highlighting their respective strengths, limitations, and suitability across administration routes and target cell populations. While adeno-associated viral vectors currently dominate clinical development, emerging non-viral systems, such as lipid-based formulations, polyplexes, exosomes, and peptide-based carriers, offer complementary advantages in safety, payload flexibility, and repeat dosing. By integrating insights from retinal biology, biomaterials engineering, and clinical trial experience, this review offers decision-oriented guidance for selecting appropriate delivery strategies based on disease context, target cells, and translational constraints. We further discuss how advances in genome editing, administration routes, and carrier design may shape the next generation of economically viable and clinically scalable gene therapies for IRDs.