AAV2-antiVEGFscFv gene therapy for retinal neovascularization

• Published in: Molecular therapy. Methods & clinical development Vol. 31; p. 101145
• Main Authors: Han, Ni, Xu, Xin, Liu, Ying, Luo, Guangzuo
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 14.12.2023; Elsevier
• Subjects: adeno-associated virus; brolucizumab; gene therapy; retinal neovascularization; vascular endothelial growth factor; brolucizumab; gene therapy; adeno-associated virus; vascular endothelial growth factor; retinal neovascularization
• ISSN: 2329-0501; 2329-0501
• DOI: 10.1016/j.omtm.2023.101145

Retinal neovascularization (NV) may lead to irreversible vision impairment, the main treatment for which is the inhibition of vascular endothelial growth factor (VEGF). Existing drugs show limited clinical benefits because of their high prices and short half-lives, which increase the financial burden and medical risks to patients. Gene therapy on the basis of adeno-associated viruses is a promising approach to overcome these limitations because of the nonintegrative nature, low immunogenicity, and potential long-term gene expression of adeno-associated viruses. In this study, we constructed a novel recombinant adeno-associated virus with the single-chain fragment variable (scFv) fragment of the anti-VEGF antibody, AAV2-antiVEGFscFv, consisting of the VH and VL structural domains of IgG. AAV2-antiVEGFscFv effectively inhibited NV, retinal leakage, and retinal detachment in oxygen-induced retinopathy (OIR) mice, Tet/opsin/VEGF double-transgenic mice, and VEGF-induced rabbit NV models. AAV2-antiVEGFscFv also significantly suppressed VEGF-induced inflammation. Furthermore, we showed that AAV2-antiVEGFscFv could be sustainably expressed for a prolonged period and exhibited low immunotoxicity in vivo. This study indicates that AAV2-antiVEGFscFv could be a potential approach for NV treatment and provides strong support for preclinical research. [Display omitted] Luo and colleagues constructed a novel recombinant adeno-associated virus, AAV2-antiVEGFscFv, loading the scFv fragment of the anti-vascular endothelial growth factor antibody. The results of this study support further preclinical research of AAV2-antiVEGFscFv vector as potentially safe and effective long-term treatment option for NV-associated diseases.