ArticleBlood2009
Successful treatment of canine hemophilia by continuous expression of canine FVIIa.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
What it found
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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
35 citing papers in PubMed, 76 citations in OpenAlex.
- One Health: Animal Models of Heritable Human Bleeding Diseases.Animals : an open access journal from MDPI · 2022Review
- Adeno-associated virus-mediated expression of activated factor V (FVa) for hemophilia phenotypic correction.Frontiers in medicine · 2022Article
- Gene Therapy for Inherited Bleeding Disorders.Seminars in thrombosis and hemostasis · 2021Review
- Adeno-associated virus as a gene therapy vector: strategies to neutralize the neutralizing antibodies.Clinical and experimental medicine · 2019Review
- Protein-Engineered Coagulation Factors for Hemophilia Gene Therapy.Molecular therapy. Methods & clinical development · 2019Review
- Gene-based FVIIa prophylaxis modulates the spontaneous bleeding phenotype of hemophilia A rats.Blood advances · 2019Article
- Development and testing of AAV-delivered single-chain variable fragments for the treatment of methamphetamine abuse.PloS one · 2018Article
- Sustained correction of FVII deficiency in dogs using AAV-mediated expression of zymogen FVII.Blood · 2016Article
- Current animal models of hemophilia: the state of the art.Thrombosis journal · 2016Review
- The Skeletal Muscle Environment and Its Role in Immunity and Tolerance to AAV Vector-Mediated Gene Transfer.Current gene therapy · 2015Review
- Animal models: Dogged pursuit.Nature · 2014Article
- The endothelial protein C receptor enhances hemostasis of FVIIa administration in hemophilic mice in vivo.Blood · 2014Article
- Lessons Learned from Animal Models of Inherited Bleeding Disorders.Hematology education. European Hematology Association. Congress. Education Program · 2014Article
- An engineered U1 small nuclear RNA rescues splicing defective coagulation F7 gene expression in mice.Journal of thrombosis and haemostasis : JTH · 2014Article
- Portal vein delivery of viral vectors for gene therapy for hemophilia.Methods in molecular biology (Clifton, N.J.) · 2014Article
- Animal models of hemophilia and related bleeding disorders.Seminars in hematology · 2013Review
- Mapping a neutralizing epitope onto the capsid of adeno-associated virus serotype 8.Journal of virology · 2012Article
- Muscle Gene Therapy for Hemophilia.Journal of genetic syndromes & gene therapy · 2012Article
- A review of current methods for assessing hemostasis in vivo and introduction to a potential alternative approach.Thrombosis research · 2012Review
- Animal models of hemophilia.Progress in molecular biology and translational science · 2012Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Continuous expression of activated factor VII (FVIIa) via gene transfer is a potential therapeutic approach for hemophilia patients with or without inhibitory antibodies to human factor VIII (FVIII) or IX (FIX). Here, we investigate whether gene transfer of an engineered canine FVIIa (cFVIIa) transgene can affect hemostasis in a canine model of hemophilia, a good predictor of efficacy of hemophilia treatments. Purified recombinant cFVIIa exhibited 12-fold higher tissue factor-dependent activity than purified recombinant zymogen cFVII. Subsequently, we generated a serotype 8 recombinant adeno-associated viral vector expressing cFVIIa from a liver-specific promoter. Vector delivery via the portal vein in hemophilia A and B dogs was well tolerated, and long-term expression of cFVIIa resulted in a shortening of the prothrombin time, partial correction of the whole blood clotting time and thromboelastography parameters, and a complete absence of spontaneous bleeding episodes. No evidence of hepatotoxicity, thrombotic complications, or inhibitory immune response was found. These data provide the first evidence for in vivo efficacy and safety of continuously expressed FVIIa as a FVIII/FIX-bypassing agent in a large animal model of hemophilia, avoiding the risk of inhibitor formation associated with bolus FVIII or FIX infusion.
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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.