gene therapy using siena technology

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To assess the feasibility of a gene therapeutic approach to treating choroidal neovascularization (CNV), we generated an adeno-associated virus type 8 vector (AAV8) encoding a small interfering RNA (siRNA) targeting vascular endothelial growth factor (VEGF), and determined its ability to inhibit angiogenesis. We made AAV8/SmVEGF-2. We injected AAV8/SmVEGF-2 or control vector (AAV8/GFP) into the subretinal space in C57BL/6 mice. The eyes were removed for flat mount analysis of CNV surface area. Subretinal delivery of AAV8/SmVEGF-2 significantly diminished CNV at the laser lesions, as compared to AAV8/GFP Using ELISA, we found that VEGF levels were reduced by approximately half in AAV8/SmVEGF-2 treated eyes. These results suggest that siRNA-VEGF can be expressed across the retina and that long-term suppression of CNV is possible through the use of stable AAV-mediated siRNA-VEGF expression.