ArticlePLoS pathogens2024
Structural basis of the recognition of adeno-associated virus by the neurological system-related receptor carbonic anhydrase IV.
Article in PLoS pathogens, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 13 citations in OpenAlex.
- CA-IV-directed small-molecule shuttle enables targeted brain delivery of biologics.Nature chemical biology · 2026Article
- Systemic delivery of AAV-GFM1 corrects COXPD1 molecular alterations in Gfm1EMBO molecular medicine · 2026Article
- Lafora disease gene therapy: EPM2A but not EPM2B overexpression results in Lafora body formation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- The delivery challenge of adeno-associated virus vector-based gene therapies for neurological diseases.Frontiers in neuroscience · 2026Review
- The amazing AAV capsids: Into the structure-verse.Molecular therapy. Methods & clinical development · 2025Review
- Advances in gene therapy for Lafora disease: Intravenous recombinant adeno-associated virus-mediated delivery of EPM2A and EPM2B genes.Clinical and translational medicine · 2025Article
- Therapeutic AASS inhibition by AAV-miRNA rescues glutaric aciduria type I severe phenotype in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Article
- Transient receptor potential vanilloid channel 2 contributes to multi-modal endoplasmic reticulum and perinuclear space dilations that can also be observed in prion-infected mice.Acta neuropathologica · 2025Article
- Structural characterization of antibody-responses following Zolgensma treatment for AAV capsid engineering to expand patient cohorts.Nature communications · 2025Article
- Gene therapy rescues brain edema and motor function in a mouse model of megalencephalic leukoencephalopathy with subcortical cysts.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Protein-Based Degraders: From Chemical Biology Tools to Neo-Therapeutics.Chemical reviews · 2025Review
- Structural characterization and epitope mapping of the AAVX affinity purification ligand.Molecular therapy. Methods & clinical development · 2024Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 2 countries.
Funding
Abstract
Carbonic anhydrase IV (Car4) is a newly identified receptor that allows adeno-associated virus (AAV) 9P31 to cross the blood-brain barrier and achieve efficient infection in the central nervous system (CNS) in mouse models. However, the molecular mechanism by which engineered AAV capsids with 7-mer insertion in the variable region (VR) VIII recognize these novel cellular receptors is unknown. Here we report the cryo-EM structures of AAV9P31 and its complex with Mus musculus Car4 at atomic resolution by utilizing the block-based reconstruction (BBR) method. The structures demonstrated that Car4 binds to the protrusions at 3-fold axes of the capsid. The inserted 7-mer extends into a hydrophobic region near the catalytic center of Car4 to form stable interactions. Mutagenesis studies also identified the key residues in Car4 responsible for the AAV9P31 interaction. These findings provide new insights into the novel receptor recognition mechanism of AAV generated by directed evolution and highlight the application of the BBR method to studying the virus-receptor molecular mechanism.
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Registered trials
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