Chengchi Huang, Avinash Kaur, Liyang Ji, Hong Tian, Keith A Webster, Wei Li
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引用次数: 0
Abstract
Efforts to develop gene therapy for long-term treatment of neovascular disease are hampered by ongoing concerns that biologics against vascular endothelial growth factor (VEGF) inhibit both physiological and pathological angiogenesis and are therefore at elevated risk of adverse side effects. A potential solution is to develop disease-targeted gene therapy. Secretogranin III (Scg3), a unique disease-restricted angiogenic factor described by our group, contributes significantly to ocular neovascular disease. We have shown that Scg3 blockade with a monoclonal antibody Fab fragment (Fab) stringently inhibits pathological angiogenesis without affecting healthy vessels. Here we tested the therapeutic efficacy of adeno-associated virus (AAV)-anti-Scg3Fab to block choroidal neovascularization (CNV) induced by subretinal injection of Matrigel in a mouse model. Intravitreal AAV-anti-Scg3Fab significantly reduced CNV and suppressed CNV-associated leukocyte infiltration and macrophage activation. The efficacy and anti-inflammatory effects were equivalent to those achieved by positive control AAV-aflibercept against VEGF. Efficacies of AAV-anti-Scg3Fab and AAV-aflibercept were sustained over 4 months post AAV delivery. The findings support development of AAV-anti-Scg3 as an alternative to AAV-anti-VEGF with equivalent efficacy and potentially safer mechanism of action.
期刊介绍:
Gene Therapy covers both the research and clinical applications of novel therapeutic techniques based on a genetic component. Over the last few decades, significant advances in technologies ranging from identifying novel genetic targets that cause disease through to clinical studies, which show therapeutic benefit, have elevated this multidisciplinary field to the forefront of modern medicine.