ArticleGene therapy2023
Clinical enrollment assay to detect preexisting neutralizing antibodies to AAV6 with demonstrated transgene expression in gene therapy trials.
Article in Gene therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.
- Efficacy and Safety of Gene Therapy for RPGR Gene-Associated X-Linked Retinitis Pigmentosa: A Systematic Review and Meta-Analysis.Translational vision science & technology · 2026Pooled it
- AAV-based gene therapies for neovascular AMD.Gene therapy · 2026Review
- Immune Toxicities in AAV Gene Therapy: Overview for Clinicians.International journal of molecular sciences · 2026Review
- Overcoming matrix effects in AAV neutralization assays with a constant serum concentration approach.Gene therapy · 2026Article
- Current regulatory requirements for assessment of immunogenicity for gene therapy medicinal products.Cell reports. Medicine · 2025Review
- Pre-Existing Anti-Adeno-Associated Virus Immunity in Gene Therapy: Mechanisms, Challenges, and Potential Solutions.Human gene therapy · 2025Review
- Natural history of preexisting AAV5 antibodies in adults with hemophilia B during the lead-in of the etranacogene dezaparvovec phase 3 study.Molecular therapy. Methods & clinical development · 2025Article
- Lessons Learned from Monitoring Adeno-Associated Virus-9 Neutralizing Antibody (AAV9-NAb) Seroconversion in a Cohort of Cynomolgus Macaques (Macaca fascicularis).Journal of the American Association for Laboratory Animal Science : JAALAS · 2025Article
- Advances in Duchenne Muscular Dystrophy: Diagnostic Techniques and Dystrophin Domain Insights.International journal of molecular sciences · 2025Review
- Development of cell lines with increased susceptibility to diverse adeno-associated viral vectors to enableMolecular therapy. Methods & clinical development · 2025Article
- CoreTIA: a modular, statistically robust transduction inhibition assay for AAV neutralization.Frontiers in immunology · 2025Article
- Article
- Preexisting antibody assays for gene therapy: Considerations on patient selection cutoffs and companion diagnostic requirements.Molecular therapy. Methods & clinical development · 2024Review
- Polyfunctional T cells and unique cytokine clusters imprint the anti rAAV2/rAAV9 vector immune response.Frontiers in immunology · 2024Article
- Adeno-associated virus serotype 9 antibody seroprevalence for patients in the United States with spinal muscular atrophy.Molecular therapy. Methods & clinical development · 2023Article
- A sensitive AAV transduction inhibition assay assists evaluation of critical factors for detection and concordance of pre-existing antibodies.Molecular therapy. Methods & clinical development · 2023Article
- Comparison of Pre-existing Anti-AAV8 Total Antibody Screening and Confirmatory Assays with a Cell-Based Neutralizing Assay in Normal Human Serum.The AAPS journal · 2023Article
- Binding and neutralizing anti-AAV antibodies: Detection and implications for rAAV-mediated gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recombinant adeno-associated virus (AAV) vectors are the leading platform for gene delivery for a variety of clinical applications. Patients with preexisting antibodies to AAV are currently excluded from most AAV gene therapy trials to avoid vector neutralization and ensure response to therapy. Anti-AAV neutralizing antibodies (NAbs) are typically assessed by in vitro cell-based transduction inhibition (TI) assays. However, clinical relevance of the determined enrollment cutoff and the inherent variability of a cell-based assay present challenges for use as an enrollment screening test. Here, we describe an enrollment cutoff that was clinically validated and strategies to overcome assay challenges to enable long-term stable performance. A validated anti-AAV6 cell-based TI assay was used to support clinical enrollment across multiple investigational gene therapies and to evaluate AAV6 seroprevalence in healthy and disease populations. The clinical enrollment cutoff was determined statistically using samples collected from healthy donors, applying a 0.1% false error rate with the inclusion of a minimum significant ratio (MSR) metric and in consideration of results from in vivo mouse passive transfer studies. Our strategy for long-term monitoring and control of assay performance employed plate quality control samples flanking the predefined cutoff. An approach using donor samples was implemented to bridge different lots of critical reagents without the need to redefine the cutoff.
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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.