ArticleJournal of virology2022
Structurally Mapping Antigenic Epitopes of Adeno-associated Virus 9: Development of Antibody Escape Variants.
Article in Journal of virology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
24 citing papers in PubMed, 31 citations in OpenAlex.
- Environmental and developmental factors shape anti-AAV immunity in pigs.Gene therapy · 2026Article
- The amazing AAV capsids: Into the structure-verse.Molecular therapy. Methods & clinical development · 2025Review
- Twenty years of human bocavirus research: from an unculturable virus of unclear pathogenicity to a culturable human pathogen and gene therapy vector candidate.Clinical microbiology reviews · 2025Review
- Development of LC-MS methods for AAV capsid protein quantification and host cell protein profiling.Molecular therapy. Methods & clinical development · 2025Article
- Teaching an old vector new tricks: the surprising versatility of AAV vaccines.Journal of virology · 2025Review
- Mechanisms of AAV neutralization by human alpha-defensins.PLoS pathogens · 2025Article
- Evolving adeno-associated viruses for gene transfer to the kidney via cross-species cycling of capsid libraries.Nature biomedical engineering · 2025Article
- The curious case of AAV immunology.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Structural characterization of antibody-responses following Zolgensma treatment for AAV capsid engineering to expand patient cohorts.Nature communications · 2025Article
- Immune responses in retinal gene therapy: challenges, mechanisms, and future strategies.Frontiers in immunology · 2025Review
- Predictive power of deleterious single amino acid changes to infer on AAV2 and AAV2-13 capsids fitness.Molecular therapy. Methods & clinical development · 2024Article
- rAAV expressing a COBRA-designed influenza hemagglutinin generates a protective and durable adaptive immune response with a single dose.Journal of virology · 2024Article
- An investigation of the immune epitopes of adeno-associated virus capsid-derived peptides among hemophilia patients.Molecular therapy. Methods & clinical development · 2024Article
- Nuclear AGO2 promotes myocardial remodeling by activating ANKRD1 transcription in failing hearts.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Adeno-associated virus as a delivery vector for gene therapy of human diseases.Signal transduction and targeted therapy · 2024Review
- Redirecting AAV vectors to extrahepatic tissues.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Structure-guided AAV capsid evolution strategies for enhanced CNS gene delivery.Nature protocols · 2023Review
- Structural and antigenic characterization of the avian adeno-associated virus capsid.Journal of virology · 2023Article
- The Structures and Functions of Parvovirus Capsids and Missing Pieces: the Viral DNA and Its Packaging, Asymmetrical Features, Nonprotein Components, and Receptor or Antibody Binding and Interactions.Journal of virology · 2023Review
- Structural and functional characterization of capsid binding by anti-AAV9 monoclonal antibodies from infants after SMA gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Adeno-associated viruses (AAV) serve as vectors for therapeutic gene delivery. AAV9 vectors have been FDA approved, as Zolgensma, for the treatment of spinal muscular atrophy and are being evaluated in clinical trials for the treatment of neurotropic and musculotropic diseases. A major hurdle for AAV-mediated gene delivery is the presence of preexisting neutralizing antibodies in 40 to 80% of the general population. These preexisting antibodies can reduce therapeutic efficacy through viral neutralization and the size of the patient cohort eligible for treatment. In this study, cryo-electron microscopy and image reconstruction were used to define the epitopes of five anti-AAV9 monoclonal antibodies (MAbs), ADK9, HL2368, HL2370, HL2372, and HL2374, on the capsid surface. Three of these, ADK9, HL2370, and HL2374, bound to or near the icosahedral 3-fold axes, HL2368 bound to the 2/5-fold wall, and HL2372 bound to the region surrounding the 5-fold axes. Pseudoatomic modeling enabled the mapping and identification of antibody contact amino acids on the capsid, including S454 and P659. These epitopes overlap previously defined parvovirus antigenic sites. Capsid amino acids critical for the interactions were confirmed by mutagenesis, followed by biochemical assays testing recombinant AAV9 (rAAV9) variants capable of escaping recognition and neutralization by the parental MAbs. These variants retained parental tropism and had similar or improved transduction efficiency compared to AAV9. These engineered rAAV9 variants could expand the patient cohort eligible for AAV9-mediated gene delivery by avoiding preexisting circulating neutralizing antibodies.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.