ArticleJournal of virology2012
Mapping a neutralizing epitope onto the capsid of adeno-associated virus serotype 8.
Article in Journal of virology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 76 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
76 citing papers in PubMed, 92 citations in OpenAlex.
- Identification and Phylogenetic Characterisation of Novel Adeno-Associated Virus Capsids in Non-Human Primate Tissues.Cell proliferation · 2026Article
- The amazing AAV capsids: Into the structure-verse.Molecular therapy. Methods & clinical development · 2025Review
- Optimized genomic editing of a common Duchenne muscular dystrophy mutation in patient-derived muscle cells and a new humanized mouse model.Molecular therapy. Nucleic acids · 2025Article
- Immune Modulation Strategies in Gene Therapy: Overcoming Immune Barriers and Enhancing Efficacy.Current gene therapy · 2025Review
- Quantification of full and empty particles of adeno-associated virus vectors via a novel dual fluorescence-linked immunosorbent assay.Molecular therapy. Methods & clinical development · 2024Article
- An adeno-associated virus variant enabling efficient ocular-directed gene delivery across species.Nature communications · 2024Article
- Rationally engineered novel AAV capsids for intra-articular gene delivery.Molecular therapy. Methods & clinical development · 2024Article
- Review
- Article
- Extracellular Vesicle-Encapsulated Adeno-Associated Viruses for Therapeutic Gene Delivery to the Heart.Circulation · 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
- Antibody Binding to Recombinant Adeno Associated Virus Monitored by Charge Detection Mass Spectrometry.Analytical chemistry · 2023Article
- Transcriptomic Analysis Reveals the Inability of Recombinant AAV8 to Activate Human Monocyte-Derived Dendritic Cells.International journal of molecular sciences · 2023Article
- Review
- Phosphatidylserine-mediated oral tolerance.Cellular immunology · 2023Article
- Adeno-associated virus receptor complexes and implications for adeno-associated virus immune neutralization.Frontiers in microbiology · 2023Article
- Cryo-electron Microscopy of Adeno-associated Virus.Chemical reviews · 2022Review
- Structurally Mapping Antigenic Epitopes of Adeno-associated Virus 9: Development of Antibody Escape Variants.Journal of virology · 2022Article
- Strategies to improve safety profile of AAV vectors.Frontiers in molecular medicine · 2022Review
- Comparative structural, biophysical, and receptor binding study of true type and wild type AAV2.Journal of structural biology · 2021Article
16 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Adeno-associated viruses (AAVs) are small single-stranded DNA viruses that can package and deliver nongenomic DNA for therapeutic gene delivery. AAV8, a liver-tropic vector, has shown great promise for the treatment of hemophilia A and B. However, as with other AAV vectors, host anti-capsid immune responses are a deterrent to therapeutic success. To characterize the antigenic structure of this vector, cryo-electron microscopy and image reconstruction (cryo-reconstruction) combined with molecular genetics, biochemistry, and in vivo approaches were used to define an antigenic epitope on the AAV8 capsid surface for a neutralizing monoclonal antibody, ADK8. Docking of the crystal structures of AAV8 and a generic Fab into the cryo-reconstruction for the AAV8-ADK8 complex identified a footprint on the prominent protrusions that flank the 3-fold axes of the icosahedrally symmetric capsid. Mutagenesis and cell-binding studies, along with in vitro and in vivo transduction assays, showed that the major ADK8 epitope is formed by an AAV variable region, VRVIII (amino acids 586 to 591 [AAV8 VP1 numbering]), which lies on the surface of the protrusions facing the 3-fold axis. This region plays a role in AAV2 and AAV8 cellular transduction. Coincidently, cell binding and trafficking assays indicate that ADK8 affects a postentry step required for successful virus trafficking to the nucleus, suggesting a probable mechanism of neutralization. This structure-directed strategy for characterizing the antigenic regions of AAVs can thus generate useful information to help re-engineer vectors that escape host neutralization and are hence more efficacious.
Indexed as
Identifiers
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.