ArticleMolecular therapy. Methods & clinical development2019
Therapeutic hFIX Activity Achieved after Single AAV5-hFIX Treatment in Hemophilia B Patients and NHPs with Pre-existing Anti-AAV5 NABs.
Article in Molecular therapy. Methods & clinical development, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
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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.
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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.
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Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 121 citations in OpenAlex.
- A systematic review of immunosuppressive protocols used in AAV gene therapy for monogenic disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Pooled it
- Completion of phase 2b trial of etranacogene dezaparvovec gene therapy in patients with hemophilia B over 5 years.Blood advances · 2025Trial
- Clinical immunogenicity in rAAV gene therapy: Insights and implications.Molecular therapy. Advances · 2026Review
- Seroprevalence of anti-AAV neutralizing antibodiesin healthy and retinitis pigmentosa cohorts: A multi-province study in China.Molecular therapy. Advances · 2026Article
- Hemophilia B gene therapy: a NAb-solute barrier overcome by adeno-associated virus serotype 5.Research and practice in thrombosis and haemostasis · 2026Article
- Etranacogene dezaparvovec in people with hemophilia B with preexisting adeno-associated virus 5 neutralizing antibodies: 4-year subgroup results from the HOPE-B trial.Research and practice in thrombosis and haemostasis · 2026Article
- Advancements in CRISPR-basedFrontiers in genome editing · 2026Review
- A Paradigm Shift in Hemophilia Care: The Promise of Gene Therapy.Current gene therapy · 2026Review
- Impact of pre-existing immunity on safety and biodistribution of a single AAV9 vector intrathecal injection in cynomolgus monkeys.Molecular therapy. Methods & clinical development · 2025Article
- Modified AAV5 capsid for improved brain biodistribution following direct injection in preclinical models.Molecular therapy. Methods & clinical development · 2025Article
- 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
- Sustained high expression of human FVII following AAV8-mediated gene delivery in mice.Molecular therapy. Methods & clinical development · 2025Article
- Exploring AAV-Mediated Gene Therapy for Inner Ear Diseases: from Preclinical Success to Clinical Potential.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Gene therapy as an innovative approach to the treatment of hemophilia B-a review.Journal of applied genetics · 2025Review
- Cardiac-Targeted AAV5-S100A1 Gene Therapy Protects Against Adverse Remodeling and Contractile Dysfunction in Postischemic Hearts.Circulation. Heart failure · 2025Article
- Gene therapy for hemophilia - From basic science to first approvals of "one-and-done" therapies.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Review
- Preclinical biodistribution and toxicology assessment of an AAV5-based subretinal modifier gene therapy for retinitis pigmentosa.Frontiers in medicine · 2025Article
- Gene therapy in hemophilia: the dawn of a new era.Research and practice in thrombosis and haemostasis · 2025Review
18 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Currently, individuals with pre-existing neutralizing antibodies (NABs) against adeno-associated virus (AAV) above titer of 5 are excluded from systemic AAV-based clinical trials. In this study we explored the impact of pre-existing anti-AAV5 NABs on the efficacy of AAV5-based gene therapy. AMT-060 (AAV5-human FIX) was evaluated in 10 adults with hemophilia B who tested negative for pre-existing anti-AAV5 NABs using a GFP-based assay. In this study, using a more sensitive luciferase-based assay, we show that 3 of those 10 patients tested positive for anti-AAV5 NABs. However, no relationship was observed between the presence of pre-treatment anti-AAV5 NABs and the therapeutic efficacy of AMT-060. Further studies in non-human primates (NHPs) showed that AAV5 transduction efficacy was similar following AMT-060 treatment, irrespective of the pre-existing anti-AAV5 NABs titers. We show that therapeutic efficacy of AAV5-mediated gene therapy was achieved in humans with pre-existing anti-AAV5 NABs titers up to 340. Whereas in NHPs circulating human factor IX (hFIX) protein was achieved, at a level therapeutic in humans, with pre-existing anti-AAV5 NABs up to 1030. Based on those results, no patients were excluded from the AMT-061 (AAV5-hFIX-Padua) phase IIb clinical trial (n = 3). All three subjects presented pre-existing anti-AAV5 NABs, yet had therapeutic hFIX activity after AMT-061 administration.
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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.