Ocular Delivery of Viral Vectors for Retinal and Choroidal Vascular Diseases: A Review.

Retinal and choroidal vascular diseases constitute a public health issue of global significance due to their high rates of occurrence and considerable treatment burden. A myriad of diseases fall under this umbrella term, all characterized by aberrant neovascularization and retinal edema in these ocular structures, with the current standard of care involving expensive and repeated injections of antiangiogenic protein therapeutics into the vitreous. In recent decades, gene therapy-the introduction of genetic material into patients for therapeutic benefit-has garnered notice as a safe and potentially single-injection strategy to treat ocular diseases. In particular, adeno-associated virus (AAV) is considered the most promising viral gene delivery tool because of its relatively low immunogenicity, nonintegrating nature, and versatility, and as a result a wide range of AAV-based therapies are currently under investigation in clinical trials. We survey the clinical landscape of AAV-based gene therapies for retinal and choroidal vascular diseases, including current state-of-the-art retinal-targeting AAV capsids and therapeutic cargos, with a special focus on low-risk intravitreal delivery methods. We summarize key ongoing and recent clinical studies, comment on the challenges and limitations presented therein, and detail important considerations for regulatory approval and eventual commercialization.