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H. Wang, S. Yang, J. Bennett; Suppression of Ocular Neovascularizatoin With Lentivirus–Mediated Delivery of HIF1 Short Hairpin RNA . Invest. Ophthalmol. Vis. Sci. 2006;47(13):842.
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To evaluate the ability of a lentivirus–vectored short hairpin (sh)RNA directed against HIF1á to inhibit retinal and choroidal neovascularization in vitro and in vivo in animal models.
We tested for specificity and efficiency of silencing of HIF1a.RNA using HIF1a.shRNA in 3 different human vascular endothelial cell lines. We also evaluated the effect of injection of lenti.HIF1a.shRNA on neovascularization in animal models of both choroidal neovascularization (CNV) and retinopathy of prematurity (ROP). Lenti.GFP was used as control to evaluate the efficiency of retinal transduction.
HIF1 a.shRNA can specifically and efficiently silence HIF1 a mRNA and protein
expression in endothelial cell lines. Injection of lenti.HIF1a.shRNA resulted in significant reduction of neovascularization in animal models of both CNV and ROP. Lentivirus transduced a wider array of retinal cells in diseased retinas than in normal retinas.
Vectored delivery of RNAi specific to HIF1 a may ultimately have clinical application in the treatment of acute and chronic blinding ocular neovascular disease.
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