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Abstract

Aberrant growth of blood vessels (neovascularization) is a keyfeature of severe eye diseases that can cause legal blindness,including neovascular age-related macular degeneration(nAMD) and diabetic retinopathy (DR). The development ofanti-vascular endothelial growth factor (VEGF) agents hasrevolutionized the treatment of ocular neovascularization.Novel proangiogenic targets, such as angiopoietin andplatelet-derived growth factor (PDGF), are under developmentfor patients who respond poorly to anti-VEGF therapy and toreduce adverse effects from long-term VEGF inhibition. Arapidly advancing area is gene therapy, which may provide significanttherapeutic benefits. Viral vector-mediated transgenedelivery provides the potential for continuous production ofantiangiogenic proteins, which would avoid the need forrepeated anti-VEGF injections. Gene silencing with RNA interferenceto target ocular angiogenesis has been investigated inclinical trials. Proof-of-concept gene therapy studies usinggene-editing tools such as CRISPR-Cas have already beenshown to be effective in suppressing neovascularization in animalmodels, highlighting the therapeutic potential of the systemfor treatment of aberrant ocular angiogenesis. This reviewprovides updates on the development of anti-VEGF agents andnovel antiangiogenic targets. We also summarize current genetherapy strategies already in clinical trials and those with thelatest approaches utilizing CRISPR-Cas gene editing againstaberrant ocular neovascularization.

Item Type:	Article
Authors/Creators:	Lin, F-L and Wang, P-Y and Chuang, Y-F and Wang, J-H and Wong, VHY and Bui, BV and Liu, G-S
Keywords:	ocular neovascularisation, VEGF, age-related macular degeneration, diabetic retinopathy, eye, gene therapy, neovascularization
Journal or Publication Title:	Molecular Therapy
Publisher:	Academic Press Inc Elsevier Science
ISSN:	1525-0016
DOI / ID Number:	https://doi.org/10.1016/j.ymthe.2020.06.029
Copyright Information:	Copyright 2020 The American Society of Gene and Cell Therapy
Related URLs:	Google Scholar: Liu, G-S UTAS Profile: Liu, G-S
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