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TitleAn adeno-associated virus variant enabling efficient ocular-directed gene delivery across species.
Journal, issue, pagesNat Commun, Vol. 15, Issue 1, Page 3780, Year 2024
Publish dateMay 6, 2024
AuthorsShuang 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 /
PubMed AbstractRecombinant 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.
External linksNat Commun / PubMed:38710714 / PubMed Central
MethodsEM (single particle)
Resolution2.08 Å
Structure data

EMDB-36594, PDB-8jre:
Cryo-EM structure of a designed AAV8-based vector
Method: EM (single particle) / Resolution: 2.08 Å

Source
  • adeno-associated virus - 8
KeywordsVIRUS / AAV8

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