AAV2-antiVEGFscFv gene therapy for retinal neovascularization

Area of Science:

• Ophthalmology
• Gene Therapy
• Immunology

Background:

• Retinal neovascularization (NV) causes irreversible vision impairment.
• Current treatments targeting vascular endothelial growth factor (VEGF) have limitations including high cost and short efficacy.
• Adeno-associated virus (AAV) gene therapy presents a promising alternative due to its safety and long-term expression.

Purpose of the Study:

• To develop and evaluate a novel recombinant adeno-associated virus (AAV) vector carrying an anti-VEGF single-chain variable fragment (scFv) for treating retinal neovascularization.
• To assess the efficacy and safety of AAV2-antiVEGFscFv in preclinical models of retinal neovascularization.

Main Methods:

• Construction of a recombinant AAV vector, AAV2-antiVEGFscFv, encoding the anti-VEGF scFv.
• Evaluation of AAV2-antiVEGFscFv in oxygen-induced retinopathy (OIR) mice, Tet/opsin/VEGF double-transgenic mice, and VEGF-induced rabbit NV models.
• Assessment of NV inhibition, retinal leakage, retinal detachment, inflammation suppression, long-term expression, and immunotoxicity in vivo.

Main Results:

• AAV2-antiVEGFscFv effectively inhibited NV, retinal leakage, and detachment in multiple preclinical models.
• The treatment significantly suppressed VEGF-induced inflammation.
• Sustained expression and low immunotoxicity of AAV2-antiVEGFscFv were demonstrated in vivo.

Conclusions:

• AAV2-antiVEGFscFv is a potent therapeutic candidate for retinal neovascularization.
• This gene therapy approach shows potential for long-term efficacy and safety in treating vision-threatening conditions.
• The study provides strong preclinical support for AAV-based anti-VEGF gene therapy in ophthalmology.