Gene Therapy Intervention in Neovascular Eye Disease: A Recent Update.

Abstract Aberrant growth of blood vessels (neovascularization) is a key feature of severe eye diseases that can cause legal blindness, including neovascular age-related macular degeneration (AMD) and diabetic retinopathy (DR). The development of anti-vascular endothelial growth factor (VEGF) agents has revolutionized the treatment of ocular neovascularization. Novel proangiogenic targets, such as angiopoietin and platelet-derived growth factor (PDGF), are under development for patients who respond poorly to anti-VEGF therapy and to reduce adverse effects from long-term VEGF inhibition. A rapidly advancing area is gene therapy, which may provide significant therapeutic benefits. Viral vector-mediated transgene delivery provides the potential for continuous production of anti-angiogenic proteins, which would avoid the need for repeated anti-VEGF injections. Gene silencing with RNA interference to target ocular angiogenesis has been investigated in clinical trials. Proof-of-concept gene therapy studies using gene-editing tools such as CRISPR/Cas have already shown to be effective in suppressing neovascularization in animal models, highlighting the therapeutic potential of this system for treatment of aberrant ocular angiogenesis. This review provides updates on the development of anti-VEGF agents and novel anti-angiogenic targets. We also summarize current gene therapy strategies already in clinical trials and those the latest approaches utilizing CRISPR/Cas gene editing against aberrant ocular neovascularization.