ArticleMolecular therapy. Methods & clinical development2016
Effects of FVIII immunity on hepatocyte and hematopoietic stem cell-directed gene therapy of murine hemophilia A.
Article in Molecular therapy. Methods & clinical development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
What it found
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The trial behind it
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Who cites it
21 citing papers in PubMed, 24 citations in OpenAlex.
- Evaluation of Maternal Safety Following Prenatal Cell and Gene Therapy for Hemophilia A.Prenatal diagnosis · 2026Article
- Transplanted gene-modified placental cells boost FVIII activity in pediatric sheep without eliciting immunity, toxicity, or adverse events.Frontiers in immunology · 2025Article
- Ultrasound-mediated gene delivery specifically targets liver sinusoidal endothelial cells for sustained FVIII expression in hemophilia A mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Transplanting FVIII/ET3-secreting cells in fetal sheep increases FVIII levels long-term without inducing immunity or toxicity.Nature communications · 2023Article
- Pharmacokinetic analysis identifies a factor VIII immunogenicity threshold after AAV gene therapy in hemophilia A mice.Blood advances · 2022Article
- Autologous bone marrow-derived MSCs engineered to express oFVIII-FLAG engraft in adult sheep and produce an effective increase in plasma FVIII levels.Frontiers in immunology · 2022Article
- Non-genotoxic conditioning facilitates hematopoietic stem cell gene therapy for hemophilia A using bioengineered factor VIII.Molecular therapy. Methods & clinical development · 2021Article
- Enhancing therapeutic efficacy of in vivo platelet-targeted gene therapy in hemophilia A mice.Blood advances · 2020Article
- The Immune Response to the fVIII Gene Therapy in Preclinical Models.Frontiers in immunology · 2020Review
- Escape or Fight: Inhibitors in Hemophilia A.Frontiers in immunology · 2020Review
- Translational Potential of Immune Tolerance Induction by AAV Liver-Directed Factor VIII Gene Therapy for Hemophilia A.Frontiers in immunology · 2020Review
- B Cell Depletion Eliminates FVIII Memory B Cells and Enhances AAV8-coF8 Immune Tolerance Induction When Combined With Rapamycin.Frontiers in immunology · 2020Article
- Adenovirus vectors in hematopoietic stem cell genome editing.FEBS letters · 2019Review
- High-level protein production in erythroid cells derived from in vivo transduced hematopoietic stem cells.Blood advances · 2019Article
- Complexity of immune responses to AAV transgene products - Example of factor IX.Cellular immunology · 2019Review
- Update on clinical gene therapy for hemophilia.Blood · 2019Review
- Preclinical Development of a Hematopoietic Stem and Progenitor Cell Bioengineered Factor VIII Lentiviral Vector Gene Therapy for Hemophilia A.Human gene therapy · 2018Article
- Target-Cell-Directed Bioengineering Approaches for Gene Therapy of Hemophilia A.Molecular therapy. Methods & clinical development · 2018Article
- Protein S: a Multifunctional Anticoagulant.Biomedical research and clinical practice · 2017Article
- Current and emerging factor VIII replacement products for hemophilia A.Therapeutic advances in hematology · 2017Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Immune responses to coagulation factors VIII (FVIII) and IX (FIX) represent primary obstacles to hemophilia treatment. Previously, we showed that hematopoietic stem cell (HSC) retroviral gene therapy induces immune nonresponsiveness to FVIII in both naive and preimmunized murine hemophilia A settings. Liver-directed adeno-associated viral (AAV)-FIX vector gene transfer achieved similar results in preclinical hemophilia B models. However, as clinical immune responses to FVIII and FIX differ, we investigated the ability of liver-directed AAV-FVIII gene therapy to affect FVIII immunity in hemophilia A mice. Both FVIII naive and preimmunized mice were administered recombinant AAV8 encoding a liver-directed bioengineered FVIII expression cassette. Naive animals receiving high or mid-doses subsequently achieved near normal FVIII activity levels. However, challenge with adjuvant-free recombinant FVIII induced loss of FVIII activity and anti-FVIII antibodies in mid-dose, but not high-dose AAV or HSC lentiviral (LV) vector gene therapy cohorts. Furthermore, unlike what was shown previously for FIX gene transfer, AAV-FVIII administration to hemophilia A inhibitor mice conferred no effect on anti-FVIII antibody or inhibitory titers. These data suggest that functional differences exist in the immune modulation achieved to FVIII or FIX in hemophilia mice by gene therapy approaches incorporating liver-directed AAV vectors or HSC-directed LV.
Identifiers
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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.