+Open data
-Basic information
Entry | Database: PDB / ID: 8jre | ||||||
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Title | Cryo-EM structure of a designed AAV8-based vector | ||||||
Components | Capsid protein | ||||||
Keywords | VIRUS / AAV8 | ||||||
Function / homology | Phospholipase A2-like domain / Phospholipase A2-like domain / Parvovirus coat protein VP2 / Parvovirus coat protein VP1/VP2 / Parvovirus coat protein VP2 / Capsid/spike protein, ssDNA virus / T=1 icosahedral viral capsid / structural molecule activity / Capsid protein Function and homology information | ||||||
Biological species | Adeno-associated virus - 8 | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 2.08 Å | ||||||
Authors | Ke, X. / Luo, S. / Zheng, Q. / Jiang, H. / Liu, F. / Sun, X. | ||||||
Funding support | 1items
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Citation | 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. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 8jre.cif.gz | 5.1 MB | Display | PDBx/mmCIF format |
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PDB format | pdb8jre.ent.gz | Display | PDB format | |
PDBx/mmJSON format | 8jre.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 8jre_validation.pdf.gz | 1.6 MB | Display | wwPDB validaton report |
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Full document | 8jre_full_validation.pdf.gz | 1.6 MB | Display | |
Data in XML | 8jre_validation.xml.gz | 626 KB | Display | |
Data in CIF | 8jre_validation.cif.gz | 1 MB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/jr/8jre ftp://data.pdbj.org/pub/pdb/validation_reports/jr/8jre | HTTPS FTP |
-Related structure data
Related structure data | 36594MC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
#1: Protein | Mass: 59270.191 Da / Num. of mol.: 60 Source method: isolated from a genetically manipulated source Source: (gene. exp.) Adeno-associated virus - 8 / Production host: Homo sapiens (human) / References: UniProt: Q8JQF8 |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: Adeno-associated virus - 8 / Type: VIRUS / Entity ID: all / Source: RECOMBINANT |
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Source (natural) | Organism: Adeno-associated virus - 8 |
Source (recombinant) | Organism: Homo sapiens (human) |
Details of virus | Empty: NO / Enveloped: NO / Isolate: OTHER / Type: VIRION |
Buffer solution | pH: 7.5 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 2400 nm / Nominal defocus min: 1200 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: FEI FALCON IV (4k x 4k) |
-Processing
CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION |
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3D reconstruction | Resolution: 2.08 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 90744 / Symmetry type: POINT |