Summary for 8JRE
| Entry DOI | 10.2210/pdb8jre/pdb |
| EMDB information | 36594 |
| Descriptor | Capsid protein (1 entity in total) |
| Functional Keywords | aav8, virus |
| Biological source | Adeno-associated virus - 8 |
| Total number of polymer chains | 60 |
| Total formula weight | 3556211.46 |
| Authors | |
| Primary citation | Luo, S.,Jiang, H.,Li, Q.,Qin, Y.,Yang, S.,Li, J.,Xu, L.,Gou, Y.,Zhang, Y.,Liu, F.,Ke, X.,Zheng, Q.,Sun, X. An adeno-associated virus variant enabling efficient ocular-directed gene delivery across species. Nat Commun, 15:3780-3780, 2024 Cited by PubMed 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 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. PubMed: 38710714DOI: 10.1038/s41467-024-48221-4 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.08 Å) |
Structure validation
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