ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
Intraosseous delivery of lentiviral vectors targeting factor VIII expression in platelets corrects murine hemophilia A.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 85 citations in OpenAlex.
- Engineering platelets as cancer therapeutics.Nature reviews. Clinical oncology · 2026Review
- Treatment of canine hemophilia A via intraosseous delivery of a platelet-specific factor VIII-lentiviral vector.Blood vessels, thrombosis & hemostasis · 2026Article
- Missense and nonsense mutations and inhibitor development in patients with hemophilia A and B.Journal of thrombosis and thrombolysis · 2026Review
- Clinical perspective: Advancing hemophilia treatment through gene therapy approaches.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Platelet-targeted gene therapy induces immune tolerance in hemophilia and beyond.Journal of thrombosis and haemostasis : JTH · 2024Review
- Dual-locus, dual-HDR editing permits efficient generation of antigen-specific regulatory T cells with robust suppressive activity.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Effect of chimeric antigen receptor T cells against protease-activated receptor 1 for treating pancreatic cancer.BMC medicine · 2023Article
- A chemically inducible IL-2 receptor signaling complex allows for effective in vitro and in vivo selection of engineered CD4+ T cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Intraosseous delivery of platelet-targeted factor VIII lentiviral vector in humanized NBSGW mice.Blood advances · 2022Article
- CRISPR/Cas-Dependent and Nuclease-FreeHuman gene therapy · 2021Review
- Gene Therapy for Inherited Bleeding Disorders.Seminars in thrombosis and hemostasis · 2021Review
- Enhancing therapeutic efficacy of in vivo platelet-targeted gene therapy in hemophilia A mice.Blood advances · 2020Article
- Engineering Chimeric Antigen Receptor T Cells against Immune Checkpoint Inhibitors PD-1/PD-L1 for Treating Pancreatic Cancer.Molecular therapy oncolytics · 2020Article
- Flow-Cytometry Platform for Intracellular Detection of FVIII in Blood Cells: A New Tool to Assess Gene Therapy Efficiency for Hemophilia A.Molecular therapy. Methods & clinical development · 2020Article
- Treatment of Hemophilia A Using Factor VIII Messenger RNA Lipid Nanoparticles.Molecular therapy. Nucleic acids · 2020Article
- Platelet-Targeted FVIII Gene Therapy Restores Hemostasis and Induces Immune Tolerance for Hemophilia A.Frontiers in immunology · 2020Review
- Advances in gene therapy for hemophilia.Journal of biosciences · 2020Review
- Escape or Fight: Inhibitors in Hemophilia A.Frontiers in immunology · 2020Review
- The Immune Response to the fVIII Gene Therapy in Preclinical Models.Frontiers in immunology · 2020Review
- A Treg-Selective IL-2 Mutein Prevents the Formation of Factor VIII Inhibitors in Hemophilia Mice Treated With Factor VIII Gene Therapy.Frontiers in immunology · 2020Article
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7 authors at 3 institutions in 1 country.
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Abstract
Intraosseous (IO) infusion of lentiviral vectors (LVs) for in situ gene transfer into bone marrow may avoid specific challenges posed by ex vivo gene delivery, including, in particular, the requirement of preconditioning. We utilized IO delivery of LVs encoding a GFP or factor VIII (FVIII) transgene directed by ubiquitous promoters (a MND or EF-1α-short element; M-GFP-LV, E-F8-LV) or a platelet-specific, glycoprotein-1bα promoter (G-GFP-LV, G-F8-LV). A single IO infusion of M-GFP-LV or G-GFP-LV achieved long-term and efficient GFP expression in Lineage(-)Sca1(+)c-Kit(+) hematopoietic stem cells and platelets, respectively. While E-F8-LV produced initially high-level FVIII expression, robust anti-FVIII immune responses eliminated functional FVIII in circulation. In contrast, IO delivery of G-F8-LV achieved long-term platelet-specific expression of FVIII, resulting in partial correction of hemophilia A. Furthermore, similar clinical benefit with G-F8-LV was achieved in animals with pre-existing anti-FVIII inhibitors. These findings further support platelets as an ideal FVIII delivery vehicle, as FVIII, stored in α-granules, is protected from neutralizing antibodies and, during bleeding, activated platelets locally excrete FVIII to promote clot formation. Overall, a single IO infusion of G-F8-LV was sufficient to correct hemophilia phenotype for long term, indicating that this approach may provide an effective means to permanently treat FVIII deficiency.
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