ArticleNature biotechnology2011
A zymogen-like factor Xa variant corrects the coagulation defect in hemophilia.
Article in Nature biotechnology, 2011. 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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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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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
39 citing papers in PubMed, 71 citations in OpenAlex.
- Factor IXa and factor X influence factor VIIIa stability and inactivation mechanisms in vitro and in vivo.Blood · 2025Article
- Blood Coagulation Factor IX: Structure, Function, and Regulation.IUBMB life · 2025Review
- Pre-clinical evaluation of an enhanced-function factor VIII variant for durable hemophilia A gene therapy in male mice.Nature communications · 2024Article
- AAV gene therapy in companion dogs with severe hemophilia: Real-world long-term data on immunogenicity, efficacy, and quality of life.Molecular therapy. Methods & clinical development · 2024Article
- Article
- Preclinical assessment of an optimized AAV-FVIII vector in mice and non-human primates for the treatment of hemophilia A.Molecular therapy. Methods & clinical development · 2022Article
- Hemostatic efficacy of marstacimab alone or in combination with bypassing agents in hemophilia plasmas and a mouse bleeding model.Research and practice in thrombosis and haemostasis · 2022Article
- Blood coagulation factor X: molecular biology, inherited disease, and engineered therapeutics.Journal of thrombosis and thrombolysis · 2021Review
- Article
- Activated factor X targeted stored in platelets as an effective gene therapy strategy for both hemophilia A and B.Clinical and translational medicine · 2021Article
- A mutated factor X activatable by thrombin corrects bleedings in vivo in a rabbit model of antibody-induced hemophilia A.Haematologica · 2020Article
- Role of the I16-D194 ionic interaction in the trypsin fold.Scientific reports · 2019Article
- Article
- Infused factor VIII-expressing platelets or megakaryocytes as a novel therapeutic strategy for hemophilia A.Blood advances · 2019Article
- Protein-Engineered Coagulation Factors for Hemophilia Gene Therapy.Molecular therapy. Methods & clinical development · 2019Review
- A function-blocking PAR4 antibody is markedly antithrombotic in the face of a hyperreactive PAR4 variant.Blood advances · 2018Article
- Novel alternate hemostatic agents for patients with inhibitors: beyond bypass therapy.Hematology. American Society of Hematology. Education Program · 2017Review
- Rendering factor Xa zymogen-like as a therapeutic strategy to treat bleeding.Current opinion in hematology · 2017Review
- Hierarchical organization of the hemostatic response to penetrating injuries in the mouse macrovasculature.Journal of thrombosis and haemostasis : JTH · 2017Article
- Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
Abstract
Effective therapies are needed to control excessive bleeding in a range of clinical conditions. We improve hemostasis in vivo using a conformationally pliant variant of coagulation factor Xa (FXa(I16L)) rendered partially inactive by a defect in the transition from zymogen to active protease. Using mouse models of hemophilia, we show that FXa(I16L) has a longer half-life than wild-type FXa and does not cause excessive activation of coagulation. Once clotting mechanisms are activated to produce its cofactor FVa, FXa(I16L) is driven to the protease state and restores hemostasis in hemophilic animals upon vascular injury. Moreover, using human or murine analogs, we show that FXa(I16L) is more efficacious than FVIIa, which is used to treat bleeding in hemophilia inhibitor patients. FXa(I16L) may provide an effective strategy to enhance blood clot formation and act as a rapid pan-hemostatic agent for the treatment of bleeding conditions.
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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.