ArticleThe Journal of clinical investigation2006
Factor VIII ectopically targeted to platelets is therapeutic in hemophilia A with high-titer inhibitory antibodies.
Article in The Journal of clinical investigation, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 100 papers.
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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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Who cites it
100 citing papers in PubMed, 188 citations in OpenAlex.
- FVIII-containing platelets modulate immune responses and attenuate inhibitor development in hemophilia A mice.Haematologica · 2026Article
- Impact of antiplatelet therapy on the hemostatic efficacy of platelet-targeted FVIII gene therapy in hemophilia A mice.Blood advances · 2026Article
- Missense and nonsense mutations and inhibitor development in patients with hemophilia A and B.Journal of thrombosis and thrombolysis · 2026Review
- 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
- Therapeutic advances in hemophilia: from molecular innovation to patient-centered global care.Frontiers in medicine · 2025Review
- Chemokine CXCL13 facilitates anti-FVIII inhibitory antibody development in hemophilia A patients and murine models.International immunopharmacology · 2024Article
- Evaluating clinically translatable conditioning for platelet gene therapy in murine hemophilia A with inhibitors.Journal of thrombosis and haemostasis : JTH · 2024Article
- Recent Advances in Gene Therapy for Hemophilia: Projecting the Perspectives.Biomolecules · 2024Review
- Platelet-targeted gene therapy induces immune tolerance in hemophilia and beyond.Journal of thrombosis and haemostasis : JTH · 2024Review
- Characteristics of FXa-storing platelets in hemophilia B mice and the influence of alcohol on the platelets.Scientific reports · 2023Article
- Pre-existing anti-factor VIII immunity alters therapeutic platelet-targeted factor VIII engraftment following busulfan conditioning through cytotoxic CD8 T cells.Journal of thrombosis and haemostasis : JTH · 2023Article
- Adeno-Associated Virus Gene Therapy for Hemophilia.Annual review of medicine · 2023Review
- Desialylated Platelet Clearance in the Liver is a Novel Mechanism of Systemic Immunosuppression.Research (Washington, D.C.) · 2023Article
- A novel mouse model of type 2N VWD was developed by CRISPR/Cas9 gene editing and recapitulates human type 2N VWD.Blood advances · 2022Article
- Targeting transmembrane-domain-less MOG expression to platelets prevents disease development in experimental autoimmune encephalomyelitis.Frontiers in immunology · 2022Article
- Hemophilia gene therapy: ushering in a new treatment paradigm?Hematology. American Society of Hematology. Education Program · 2021Review
- Platelet-targeted hyperfunctional FIX gene therapy for hemophilia B mice even with preexisting anti-FIX immunity.Blood advances · 2021Article
- Platelet gene therapy induces robust immune tolerance even in a primed model via peripheral clonal deletion of antigen-specific T cells.Molecular therapy. Nucleic acids · 2021Article
- Activated factor X targeted stored in platelets as an effective gene therapy strategy for both hemophilia A and B.Clinical and translational medicine · 2021Article
- Current Clinical Applications of In Vivo Gene Therapy with AAVs.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
40 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
Abstract
Inhibitory immune response to exogenously infused factor VIII (FVIII) is a major complication in the treatment of hemophilia A. Generation of such inhibitors has the potential to disrupt gene therapy for hemophilia A. We explore what we believe to be a novel approach to overcome this shortcoming. Human B-domain-deleted FVIII (hBDDFVIII) was expressed under the control of the platelet-specific alphaIIb promoter in platelets of hemophilic (FVIIInull) mice to create 2bF8trans mice. The FVIII transgene product was stored in platelets and released at the site of platelet activation. In spite of the lack of FVIII in the plasma of 2bF8trans mice, the bleeding phenotype of FVIIInull mice was corrected. More importantly, the bleeding phenotype was corrected in the presence of high inhibitory antibody titers introduced into the mice by infusion or by spleen cell transfer from recombinant hBDDFVIII-immunized mice. Our results demonstrate that this approach to the targeted expression of FVIII in platelets has the potential to correct hemophilia A, even in the presence of inhibitory immune responses to infused FVIII.
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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.