ArticleBlood2009
Correction of murine hemophilia A following nonmyeloablative transplantation of hematopoietic stem cells engineered to encode an enhanced human factor VIII variant using a safety-augmented retroviral vector.
Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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.
The trial behind it
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
11 citing papers in PubMed, 30 citations in OpenAlex.
- Ultrasound-mediated gene delivery of factor VIII plasmids for hemophilia A gene therapy in mice.Molecular therapy. Nucleic acids · 2022Article
- Extrahepatic sources of factor VIII potentially contribute to the coagulation cascade correcting the bleeding phenotype of mice with hemophilia A.Haematologica · 2015Article
- Gene therapy for hemophilia.Frontiers in bioscience (Landmark edition) · 2015Review
- Development of Gene Transfer for Induction of Antigen-specific Tolerance.Molecular therapy. Methods & clinical development · 2014Article
- piggyBac-mediated phenotypic correction of factor VIII deficiency.Molecular therapy. Methods & clinical development · 2014Article
- Article
- Gene therapy for haemophilia: prospects and challenges to prevent or reverse inhibitor formation.British journal of haematology · 2012Review
- Ectopic platelet-delivered factor (F) VIII for the treatment of Hemophilia A: Plasma and platelet FVIII, is it all the same?Journal of genetic syndromes & gene therapy · 2011Article
- Factor VIII delivered by haematopoietic stem cell-derived B cells corrects the phenotype of haemophilia A mice.Thrombosis and haemostasis · 2011Article
- Article
- Delivery of nucleic acid therapeutics by genetically engineered hematopoietic stem cells.Advanced drug delivery reviews · 2010Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Insertional mutagenesis by retroviral vectors is a major impediment to the clinical application of hematopoietic stem cell gene transfer for the treatment of hematologic disorders. We recently developed an insulated self-inactivating gammaretroviral vector, RMSinOFB, which uses a novel enhancer-blocking element that significantly decreases genotoxicity of retroviral integration. In this study, we used the RMSinOFB vector to evaluate the efficacy of a newly bioengineered factor VIII (fVIII) variant (efVIII)--containing a combination of A1 domain point mutations (L303E/F309S) and an extended partial B domain for improved secretion plus A2 domain mutations (R484A/R489A/P492A) for reduced immunogenicity--toward successful treatment of murine hemophilia A. In cell lines, efVIII was secreted at up to 6-fold higher levels than an L303E/F309S A1 domain-only fVIII variant (sfVIIIDeltaB). Most important, when compared with a conventional gammaretroviral vector expressing sfVIIIDeltaB, lower doses of RMSin-efVIII-OFB-transduced hematopoietic stem cells were needed to generate comparable curative fVIII levels in hemophilia A BALB/c mice after reduced-intensity total body irradiation or nonmyeloablative chemotherapy conditioning regimens. These data suggest that the safety-augmented RMSin-efVIII-OFB platform represents an encouraging step in the development of a clinically appropriate gene addition therapy for hemophilia A.
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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.