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• W2783373669 abstract "Gene therapy is a promising approach in the treatment of inherited and common complex disorders of the retina. Preclinical and clinical studies have validated the use of adeno-associated viral vectors (AAV) as a safe and efficient delivery vehicle for gene transfer. Retinal pigment epithelium and rods-and to a lesser extent, cone photoreceptors-can be efficiently targeted with AAV. Other retinal cell types however are more challenging targets. The aim of this study was to characterize the transduction profile and efficiency of in silico designed, synthetic Anc80 AAVs for retinal gene transfer. Three Anc80 variants were evaluated for retinal targeting in mice and primates following subretinal delivery. In the murine retina Anc80L65 demonstrated high level of retinal pigment epithelium and photoreceptor targeting with comparable cone photoreceptor affinity compared to other AAVs. Remarkably, Anc80L65 enhanced transduction kinetics with visible expression as early as day 1 and steady state mRNA levels at day 3. Inner retinal tropism of Anc80 variants demonstrated distinct transduction patterns of Müller glia, retinal ganglion cells and inner nuclear layer neurons. Finally, murine findings with Anc80L65 qualitatively translated to the Rhesus macaque in terms of cell targets, levels and onset of expression. Our findings support the use of Anc80L65 for therapeutic subretinal gene delivery." @default.
• W2783373669 created "2018-01-26" @default.
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• W2783373669 date "2018-07-01" @default.
• W2783373669 modified "2023-10-03" @default.
• W2783373669 title "Synthetic Adeno-Associated Viral Vector Efficiently Targets Mouse and Nonhuman Primate Retina <i>In Vivo</i>" @default.
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• W2783373669 doi "https://doi.org/10.1089/hum.2017.154" @default.
• W2783373669 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6066192" @default.
• W2783373669 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/29325457" @default.
• W2783373669 hasPublicationYear "2018" @default.
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