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• W2740400511 abstract "Lentivirus-based vectors have been used for the development of potent gene therapies. Here, application of a multigenic lentiviral vector (LV) producing multiple anti-angiogenic microRNAs following subretinal delivery in a laser-induced choroidal neovascularization (CNV) mouse model is presented. This versatile LV, carrying back-to-back RNApolII-driven expression cassettes, enables combined expression of microRNAs targeting vascular endothelial growth factor A (Vegfa) mRNA and fluorescent reporters. In addition, by including a vitelliform macular dystrophy 2 (VMD2) promoter, expression of microRNAs is restricted to the retinal pigment epithelial (RPE) cells. Six days post injection (PI), robust and widespread fluorescent signals of eGFP are already observed in the retina by funduscopy. The eGFP expression peaks at day 21 PI and persists with stable expression for at least 9 months. In parallel, prominent AsRED co-expression, encoded from the VMD2-driven microRNA expression cassette, is evident in retinal sections and flat-mounts, revealing RPE-specific expression of microRNAs. Furthermore, LV-delivered microRNAs targeting the Vegfa gene in RPE cells reduced the size of laser-induced CNV in mice 28 days PI, as a consequence of diminished VEGF levels, suggesting that LVs delivered locally are powerful tools in the development of gene therapy-based strategies for treatment of age-related macular degeneration." @default.
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• W2740400511 date "2017-08-01" @default.
• W2740400511 modified "2023-10-01" @default.
• W2740400511 title "Suppression of Choroidal Neovascularization in Mice by Subretinal Delivery of Multigenic Lentiviral Vectors Encoding Anti-Angiogenic MicroRNAs" @default.
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• W2740400511 doi "https://doi.org/10.1089/hgtb.2017.079" @default.
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