ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
Structural and functional characterization of capsid binding by anti-AAV9 monoclonal antibodies from infants after SMA gene therapy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Cross-Neutralizing and Broadly Neutralizing Human Antibodies Against Nonenveloped Viruses.European journal of immunology · 2026Review
- Directed evolution of novel AAV capsids for enhanced delivery to mouse and human Schwann cells.Molecular therapy. Nucleic acids · 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
- Article
- Wild-type and engineered adeno-associated viral vectors produce comparable opsin expression and light-evoked responses in rat skeletal muscle.Molecular therapy. Methods & clinical development · 2025Article
- Advances in viral vector-based delivery systems for gene therapy: a comprehensive review.3 Biotech · 2025Review
- 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
- The Structural, Biophysical, and Antigenic Characterization of the Goose Parvovirus Capsid.Microorganisms · 2025Article
- AAVolve: Concatenated long-read deep sequencing enables whole capsid tracking during shuffled AAV library selection.Molecular therapy. Methods & clinical development · 2024Article
- AAV-NRIP gene therapy ameliorates motor neuron degeneration and muscle atrophy in ALS model mice.Skeletal muscle · 2024Article
- Prenatal AAV9-GFP administration in fetal lambs results in transduction of female germ cells and maternal exposure to virus.Molecular therapy. Methods & clinical development · 2024Article
- Dissecting positive selection events and immunological drives during the evolution of adeno-associated virus lineages.PLoS pathogens · 2024Article
- [A recombinant adeno-associated virus expressing secretory TGF-β type Ⅱ receptor inhibits triple-negative murine breast cancer 4T1 cell proliferation and lung metastasis in mice].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Harnessing whole human liver ex situ normothermic perfusion for preclinical AAV vector evaluation.Nature communications · 2024Article
- Redirecting AAV vectors to extrahepatic tissues.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Gene therapy-based strategies for spinal muscular atrophy-an Asia-Pacific perspective.Molecular and cellular pediatrics · 2023Review
- Structural and antigenic characterization of the avian adeno-associated virus capsid.Journal of virology · 2023Article
- Immune Responses to Muscle-Directed Adeno-Associated Viral Gene Transfer in Clinical Studies.Human gene therapy · 2023Review
Corrections and comments
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Authors and funding
17 authors at 5 institutions in 2 countries.
Funding
Abstract
Success in the treatment of infants with spinal muscular atrophy (SMA) underscores the potential of vectors based on adeno-associated virus (AAV). However, a major obstacle to the full realization of this potential is pre-existing natural and therapy-induced anti-capsid humoral immunity. Structure-guided capsid engineering is one possible approach to surmounting this challenge but necessitates an understanding of capsid-antibody interactions at high molecular resolution. Currently, only mouse-derived monoclonal antibodies (mAbs) are available to structurally map these interactions, which presupposes that mouse and human-derived antibodies are functionally equivalent. In this study, we have characterized the polyclonal antibody responses of infants following AAV9-mediated gene therapy for SMA and recovered 35 anti-capsid mAbs from the abundance of switched-memory B (smB) cells present in these infants. For 21 of these mAbs, seven from each of three infants, we have undertaken functional and structural analysis measuring neutralization, affinities, and binding patterns by cryoelectron microscopy (cryo-EM). Four distinct patterns were observed akin to those reported for mouse-derived mAbs, but with early evidence of differing binding pattern preference and underlying molecular interactions. This is the first human and largest series of anti-capsid mAbs to have been comprehensively characterized and will prove to be powerful tools for basic discovery and applied purposes.
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Registered trials
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