ArticleEMBO molecular medicine2013
Liver gene therapy by lentiviral vectors reverses anti-factor IX pre-existing immunity in haemophilic mice.
Article in EMBO molecular medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 56 citations in OpenAlex.
- Engineering B cells to treat and study human disease.Nature biotechnology · 2025Review
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- Viral Vector Based Immunotherapy for Peanut Allergy.Viruses · 2024Review
- LSpECifying transgene expression.Molecular therapy. Nucleic acids · 2024Article
- Hierarchically tumor-activated nanoCRISPR-Cas13a facilitates efficient microRNA disruption for multi-pathway-mediated tumor suppression.Theranostics · 2023Article
- Editing T cell repertoire by thymic epithelial cell-directed gene transfer abrogates risk of type 1 diabetes development.Molecular therapy. Methods & clinical development · 2022Article
- Platelet-targeted hyperfunctional FIX gene therapy for hemophilia B mice even with preexisting anti-FIX immunity.Blood advances · 2021Article
- Immune Responses to Viral Gene Therapy Vectors.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Review
- B Cell Depletion Eliminates FVIII Memory B Cells and Enhances AAV8-coF8 Immune Tolerance Induction When Combined With Rapamycin.Frontiers in immunology · 2020Article
- Translational Potential of Immune Tolerance Induction by AAV Liver-Directed Factor VIII Gene Therapy for Hemophilia A.Frontiers in immunology · 2020Review
- The Immune Response to the fVIII Gene Therapy in Preclinical Models.Frontiers in immunology · 2020Review
- Modulation of immune responses in lentiviral vector-mediated gene transfer.Cellular immunology · 2019Review
- Complexity of immune responses to AAV transgene products - Example of factor IX.Cellular immunology · 2019Review
- Dual muscle-liver transduction imposes immune tolerance for muscle transgene engraftment despite preexisting immunity.JCI insight · 2019Article
- Transcriptional Targeting and MicroRNA Regulation of Lentiviral Vectors.Molecular therapy. Methods & clinical development · 2019Review
- Update on clinical gene therapy for hemophilia.Blood · 2019Review
- Mesenchymal Stromal Cell-Seeded Biomimetic Scaffolds as a Factory of Soluble RANKL in Rankl-Deficient Osteopetrosis.Stem cells translational medicine · 2019Article
- Tolerance induction in hemophilia: innovation and accomplishments.Current opinion in hematology · 2018Review
- Lessons learned from lung and liver in-vivo gene therapy: implications for the future.Expert opinion on biological therapy · 2018Review
- Gene Therapy With Regulatory T Cells: A Beneficial Alliance.Frontiers in immunology · 2018Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
A major complication of factor replacement therapy for haemophilia is the development of anti-factor neutralizing antibodies (inhibitors). Here we show that liver gene therapy by lentiviral vectors (LVs) expressing factor IX (FIX) strongly reduces pre-existing anti-FIX antibodies and eradicates FIX inhibitors in haemophilia B mice. Concomitantly, plasma FIX levels and clotting activity rose to 50-100% of normal. The treatment was effective in 75% of treated mice. FIX-specific plasma cells (PCs) and memory B cells were reduced, likely because of memory B-cell depletion in response to constant exposure to high doses of FIX. Regulatory T cells displaying FIX-specific suppressive capacity were induced in gene therapy treated mice and controlled FIX-specific T helper cells. Gene therapy proved safer than a regimen mimicking immune tolerance induction (ITI) by repeated high-dose FIX protein administration, which induced severe anaphylactoid reactions in inhibitors-positive haemophilia B mice. Liver gene therapy can thus reverse pre-existing immunity, induce active tolerance to FIX and establish sustained FIX activity at therapeutic levels. These data position gene therapy as an attractive treatment option for inhibitors-positive haemophilic patients.
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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.