Language
English
Publication Date
11-1-2024
Journal
Gene Therapy
DOI
10.1038/s41434-024-00491-9
PMID
39333408
PMCID
PMC11720169
PubMedCentral® Posted Date
11-1-2025
PubMedCentral® Full Text Version
Author MSS
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.
Keywords
Choroidal Neovascularization, Animals, Dependovirus, Mice, Genetic Therapy, Collagen, Laminin, Drug Combinations, Proteoglycans, Mice, Inbred C57BL, Vascular Endothelial Growth Factor A, Disease Models, Animal, Genetic Vectors, Recombinant Fusion Proteins, Humans
Published Open-Access
yes
Recommended Citation
Huang, Chengchi; Kaur, Avinash; Ji, Liyang; et al., "Suppression of Matrigel-Induced Choroidal Neovascularization by Aav Delivery of a Novel Anti-Scg3 Antibody" (2024). Faculty and Staff Publications. 5457.
https://digitalcommons.library.tmc.edu/baylor_docs/5457