Work

Engineered RPE Cell Therapy for Controllable Anti-VEGF Delivery in Neovascular AMD

Year: 2026

Type: preprint

Abstract: Neovascularization in wet age-related macular degeneration (AMD) is caused by upregulation of vascular endothelial growth factor (VEGF-A) expression. It leads to vascular leakage, abnormal vessel growth, hemorrhage, and retinal cell death, leading to irreversible vision loss. Current anti-VEGF therapies, including Eylea® and Vabysmo®, provide clinical benefit but require frequent intravitreal injections and are limited by treatment burden, variable patient compliance, and injection-related complications. To overcome these limitations, we developed VEGF Sticky-trap, a bifunctional VEGF-binding molecule designed to anchor to the extracellular matrix (ECM) and confine anti-VEGF activity to the local ocular milieu. In this study, we engineered human retinal pigment epithelium (hRPE) cells to secrete VEGF Sticky-trap in a doxycycline-inducible manner. The modified cells generated ECM-bound Sticky-trap in vitro and, engraft long-term following subretinal transplantation. Engineered hRPE cells survived for up to 12 months, maintained inducible VEGF Sticky-trap expression, and showed no evidence of proliferation or tumor formation. This inducible cell-based platform robustly suppressed laser-induced choroidal neovascularization with efficacy comparable to recombinant VEGF-trap treatment. Importantly, despite continuous secretion, VEGF Sticky-trap remained localized to the eye and showed no detectable systemic exposure. These results establish a sustained, localized anti-VEGF delivery strategy with the potential to improve efficacy, reduce injection frequency, and enhance safety in wet AMD.

Source: Research Square

DOI: 10.21203/rs.3.rs-10021402/v1