Potential long-term inhibition of ocular neovascularisation by recombinant adeno-associated virus-mediated secretion gene therapy

Abstract

To achieve stable and localised ocular anti-angiogenic therapy, we explored the use of recombinant adeno-associated virus (rAAV)-mediated secretion gene therapy (SGT). In this study, we generated a rAAV vector encoding soluble VEGF receptor 1, sFlt-1 (AAV-CMV.sflt) and determined its ability to inhibit cautery-induced corneal NV and laser-induced cho-

Recombinant AAV-mediated gene transfer to the retina: gene therapy perspectives

“…64 It was also demonstrated that, in a similar rat model of CNV, subretinal injection of an rAAV-2 encoding soluble VEGF receptor 1 (sFlt-1) was able to suppress choroidal NV at the laser lesions. 65 These data provide evidence that intraocular expression of antiangiogenic proteins such as PEDF or sFlt-1, via rAAV vectors, may offer a new treatment for ocular neovascularization.…”

Novel anti-VEGF chimeric molecules delivered by AAV vectors for inhibition of retinal neovascularization

“…21 Subretinal delivery of AAV2 encoding full-length sFlt-1 gene has been successfully tested in mouse and in primate models of ocular neovascularization. 22,27,28 An adenoviral vector encoding full-length sFlt-1, injected both intravitreously or periocularly suppressed choroidal neovascularization at rupture sites in Bruch's membrane. 29 Our AAV2.sFLT01 vector administered intravitreally to neonatal mice significantly reduced the occurrence of neovascularization in the OIR model.…”

Subconjunctival gene delivery of the transcription factor GA-binding protein delays corneal neovascularization in a mouse model

“…[2][3][4] Various angiogenic factors mediate corneal neovascularization: vascular endothelial growth factor (VEGF), basic fibroblast growth factor, matrix metalloproteinase and insulin-like growth factor-1. Among these, VEGF is reported to be the primary mediator of neovascularization in the eye 5 and is elevated in inflamed and vascularized corneas of rats and humans. 6 Thus, reducing VEGF levels is the most common approach for inhibiting corneal neovascularization in corneal gene therapy studies.…”