Journal: Nat Commun / Year: 2024 Title: An adeno-associated virus variant enabling efficient ocular-directed gene delivery across species. Authors: Shuang Luo / Hao Jiang / Qingwei Li / Yingfei Qin / Shiping Yang / Jing Li / Lingli Xu / Yan Gou / Yafei Zhang / Fengjiang Liu / Xiao Ke / Qiang Zheng / Xun Sun / Abstract: Recombinant adeno-associated viruses (rAAVs) have emerged as promising gene therapy vectors due to their proven efficacy and safety in clinical applications. In non-human primates (NHPs), rAAVs are ...Recombinant adeno-associated viruses (rAAVs) have emerged as promising gene therapy vectors due to their proven efficacy and safety in clinical applications. In non-human primates (NHPs), rAAVs are administered via suprachoroidal injection at a higher dose. However, high doses of rAAVs tend to increase additional safety risks. Here, we present a novel AAV capsid (AAVv128), which exhibits significantly enhanced transduction efficiency for photoreceptors and retinal pigment epithelial (RPE) cells, along with a broader distribution across the layers of retinal tissues in different animal models (mice, rabbits, and NHPs) following intraocular injection. Notably, the suprachoroidal delivery of AAVv128-anti-VEGF vector completely suppresses the Grade IV lesions in a laser-induced choroidal neovascularization (CNV) NHP model for neovascular age-related macular degeneration (nAMD). Furthermore, cryo-EM analysis at 2.1 Å resolution reveals that the critical residues of AAVv128 exhibit a more robust advantage in AAV binding, the nuclear uptake and endosome escaping. Collectively, our findings highlight the potential of AAVv128 as a next generation ocular gene therapy vector, particularly using the suprachoroidal delivery route.
#200 - Aug 2016 Quasisymmetry in Icosahedral Viruses similarity (1)
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1: Capsid protein A: Capsid protein B: Capsid protein C: Capsid protein D: Capsid protein E: Capsid protein F: Capsid protein G: Capsid protein H: Capsid protein I: Capsid protein J: Capsid protein K: Capsid protein L: Capsid protein M: Capsid protein N: Capsid protein O: Capsid protein P: Capsid protein Q: Capsid protein R: Capsid protein S: Capsid protein T: Capsid protein V: Capsid protein W: Capsid protein X: Capsid protein Y: Capsid protein Z: Capsid protein 2: Capsid protein 3: Capsid protein 4: Capsid protein 5: Capsid protein 6: Capsid protein 7: Capsid protein 8: Capsid protein 9: Capsid protein a: Capsid protein b: Capsid protein c: Capsid protein d: Capsid protein e: Capsid protein f: Capsid protein g: Capsid protein h: Capsid protein i: Capsid protein j: Capsid protein l: Capsid protein k: Capsid protein m: Capsid protein n: Capsid protein o: Capsid protein p: Capsid protein q: Capsid protein r: Capsid protein s: Capsid protein t: Capsid protein u: Capsid protein v: Capsid protein w: Capsid protein x: Capsid protein y: Capsid protein z: Capsid protein
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