ArticleMolecular therapy. Methods & clinical development2020
Timing of Intensive Immunosuppression Impacts Risk of Transgene Antibodies after AAV Gene Therapy in Nonhuman Primates.
Article in Molecular therapy. Methods & clinical development, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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.
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Who cites it
38 citing papers in PubMed, 46 citations in OpenAlex.
- Antimetabolites synergize with non-genotoxic antibody drug conjugate conditioning in hematopoietic stem cell lentiviral gene therapy.Molecular therapy. Advances · 2026Article
- Reprogramming innate immunity through viral interference: A double-edged strategy for enhancing and containing gene therapies.Molecular therapy. Nucleic acids · 2026Review
- Strategies for Evading Cellular Immunity Against Recombinant AAV Vectors in Gene Therapy.Current medical science · 2026Review
- Immune Toxicities in AAV Gene Therapy: Overview for Clinicians.International journal of molecular sciences · 2026Review
- Immunogenicity of Gene and Cell Therapies.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026Review
- Enhanced Epigenetic Modulation via mRNA-Encapsulated Lipid Nanoparticles Enables Targeted Anti-inflammatory Control.ACS synthetic biology · 2026Article
- Current regulatory requirements for assessment of immunogenicity for gene therapy medicinal products.Cell reports. Medicine · 2025Review
- Transient rapamycin treatment avoids unwanted host immune responses toward AAV-delivered anti-HIV antibodies.Nature communications · 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
- Role of FoxP3Human gene therapy · 2024Review
- Viral-mediated gene therapy in pediatric neurological disorders.World journal of pediatrics : WJP · 2024Review
- Development of AAV-Mediated Gene Therapy Approaches to Treat Skeletal Diseases.Human gene therapy · 2024Review
- B cell focused transient immune suppression protocol for efficient AAV readministration to the liver.Molecular therapy. Methods & clinical development · 2024Article
- CRISPR/Cas9 Landscape: Current State and Future Perspectives.International journal of molecular sciences · 2023Review
- Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- Immunogenicity of Recombinant Adeno-Associated Virus (AAV) Vectors for Gene Transfer.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2023Review
- Advances in AAV technology for delivering genetically encoded cargo to the nonhuman primate nervous system.Current research in neurobiology · 2023Review
- Factor IX Padua for haemophilia B gene addition: universal adaptation and repeated success.The Lancet. Haematology · 2022Article
- Immunogenicity and toxicity of AAV gene therapy.Frontiers in immunology · 2022Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Adeno-associated virus (AAV) vector gene therapy is a promising treatment for a variety of genetic diseases, including hemophilia. Systemic administration of AAV vectors is associated with a cytotoxic immune response triggered against AAV capsid proteins, which if untreated can result in loss of transgene expression. Immunosuppression (IS) with corticosteroids has limited transgene loss in some AAV gene therapy clinical trials, but was insufficient to prevent loss in other studies. We used a nonhuman primate model to evaluate intensive T cell-directed IS combined with AAV-mediated transfer of the human factor IX (FIX) gene. Early administration of rabbit anti-thymocyte globulin (ATG) concomitant with AAV administration resulted in the development of anti-FIX antibodies, whereas delayed ATG by 5 weeks administration did not. The anti-FIX immune response was associated with increases in inflammatory cytokines, as well as a skewed Th17/regulatory T cell (Treg) ratio. We conclude that the timing of T cell-directed IS is critical in determining transgene-product immunogenicity or tolerance. These data have implications for systemically administered AAV gene therapy being evaluated for hemophilia A and B, as well as other genetic diseases.
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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.