ArticleMolecular therapy : the journal of the American Society of Gene Therapy2013
Minimizing the inhibitory effect of neutralizing antibody for efficient gene expression in the liver with adeno-associated virus 8 vectors.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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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
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
- rAAV immunogenicity, toxicity, and durability in 255 clinical trials: A meta-analysis.Frontiers in immunology · 2022Pooled it
- Gene therapy improves motor and mental function of aromatic l-amino acid decarboxylase deficiency.Brain : a journal of neurology · 2019Trial
- Engineering novel AAV capsids by broadly attenuated and subsequent muscle-specific tropism in mice and NHPs.Molecular therapy. Advances · 2026Article
- Advances and Challenges in Adeno-Associated Virus Gene Therapy Applications of Localized Delivery Strategies.Current medical science · 2025Review
- The curious case of AAV immunology.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Cure of Congenital Purpura Fulminans via Expression of Engineered Protein C Through Neonatal Genome Editing in Mice.Arteriosclerosis, thrombosis, and vascular biology · 2024Article
- Understanding AAV vector immunogenicity: from particle to patient.Theranostics · 2024Review
- Efficient gene transduction in pigs and macaques with the engineered AAV vector AAV.GT5 for hemophilia B gene therapy.Molecular therapy. Methods & clinical development · 2023Article
- Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- 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
- The seroprevalence of neutralizing antibodies against the adeno-associated virus capsids in Japanese hemophiliacs.Molecular therapy. Methods & clinical development · 2022Article
- Overcoming the Challenges Imposed by Humoral Immunity to AAV Vectors to Achieve Safe and Efficient Gene Transfer in Seropositive Patients.Frontiers in immunology · 2022Review
- A sensitive and reproducible cell-based assay via secNanoLuc to detect neutralizing antibody against adeno-associated virus vector capsid.Molecular therapy. Methods & clinical development · 2021Article
- Overcoming innate immune barriers that impede AAV gene therapy vectors.The Journal of clinical investigation · 2021Review
- Adeno-Associated Viruses (AAV) and Host Immunity - A Race Between the Hare and the Hedgehog.Frontiers in immunology · 2021Review
- Current Status and Challenges Associated with CNS-Targeted Gene Delivery across the BBB.Pharmaceutics · 2020Review
- Utility of microminipigs for evaluating liver-mediated gene expression in the presence of neutralizing antibody against vector capsid.Gene therapy · 2020Article
- Development of New Strategies Using Extracellular Vesicles Loaded with Exogenous Nucleic Acid.Pharmaceutics · 2020Review
- Immune Response Mechanisms against AAV Vectors in Animal Models.Molecular therapy. Methods & clinical development · 2020Review
- Gene Therapy for Hemophilia: Facts and Quandaries in the 21st Century.Mediterranean journal of hematology and infectious diseases · 2020Review
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neutralizing antibodies (NAbs) against adeno-associated viruses (AAVs) are known to interfere with AAV vector-mediated gene transfer by intravascular delivery. Evading the inhibitory effects of antibodies against AAV vectors is necessary for efficient transfer of therapeutic genes clinically. For this purpose, we tested the efficacy of saline flushing in order to avoid contact of vectors with NAbs present in blood. Direct injection of the AAV8 vector carrying the factor IX (FIX) gene into the portal vein of macaques using saline flushing achieved transgene-derived FIX expression (4.7 ± 2.10-10.1 ± 5.45% of normal human FIX concentration) in the presence of NAbs. Expression was as efficient as that (5.43 ± 2.59-12.68 ± 4.83%) in macaques lacking NAbs. We next tested the efficacy of saline flushing using less invasive balloon catheter-guided injection. This approach also resulted in efficient expression of transgene-derived FIX (2.5 ± 1.06-9.0 ± 2.37%) in the presence of NAbs (14-56× dilutions). NAbs at this range of titers reduced the efficiency of transduction in the macaque liver by 100-fold when the same vector was injected into mesenteric veins without balloon catheters. Our results suggest that portal vein-directed vector delivery strategies with flushing to remove blood are efficacious for minimizing the inhibitory effect of anti-AAV antibodies.
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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.