Abstract
Currently there are no viable treatment options for patients with debilitating inherited retinal degeneration. The vast variability in disease-inducing mutations and resulting phenotypes has hampered the development of therapeutic interventions. Gene therapy is a logical approach, and recent work has focused on ways to optimize vector design and packaging to promote optimized expression and phenotypic rescue after intraocular delivery. In this review, we discuss ongoing ocular clinical trials, which currently use viral gene delivery, but focus primarily on new advancements in optimizing the efficacy of non-viral gene delivery for ocular diseases. Non-viral delivery systems are highly customizable, allowing functionalization to improve cellular and nuclear uptake, bypassing cellular degradative machinery, and improving gene expression in the nucleus. Non-viral vectors often yield transgene expression levels lower than viral counterparts, however their favorable safety/immune profiles and large DNA capacity (critical for the delivery of large ocular disease genes) make their further development a research priority. Recent work on particle coating and vector engineering presents exciting ways to overcome limitations of transient/low gene expression levels, but also highlights the fact that further refinements are needed before use in the clinic.