ArticleHuman gene therapy2009
Comparison of factor VIII transgenes bioengineered for improved expression in gene therapy of hemophilia A.
Article in Human gene therapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 47 citations in OpenAlex.
- Hemophilia A: An Ideal Disease for Prenatal Therapy.Prenatal diagnosis · 2025Review
- Comparison of different gene addition strategies to modify placental derived-mesenchymal stromal cells to produce FVIII.Frontiers in immunology · 2022Article
- Identification of coagulation factor IX variants with enhanced activity through ancestral sequence reconstruction.Blood advances · 2021Article
- Investigating Optimal Autologous Cellular Platforms for Prenatal or Perinatal Factor VIII Delivery to Treat Hemophilia A.Frontiers in cell and developmental biology · 2021Article
- Minimal Essential Human Factor VIII Alterations Enhance Secretion and Gene Therapy Efficiency.Molecular therapy. Methods & clinical development · 2020Article
- Defining the Optimal FVIII Transgene for Placental Cell-Based Gene Therapy to Treat Hemophilia A.Molecular therapy. Methods & clinical development · 2020Article
- Evaluation of the activity levels of rat FVIII and human FVIII delivered by adeno-associated viral vectors both in vitro and in vivo.Blood cells, molecules & diseases · 2018Article
- Evaluation of the biological differences of canine and human factor VIII in gene delivery: implications in human hemophilia treatment.Gene therapy · 2016Article
- Potential for cellular stress response to hepatic factor VIII expression from AAV vector.Molecular therapy. Methods & clinical development · 2016Article
- Expanding the ortholog approach for hemophilia treatment complicated by factor VIII inhibitors.Journal of thrombosis and haemostasis : JTH · 2015Article
- Gene therapy for hemophilia.Frontiers in bioscience (Landmark edition) · 2015Review
- Bioengineered coagulation factor VIII enables long-term correction of murine hemophilia A following liver-directed adeno-associated viral vector delivery.Molecular therapy. Methods & clinical development · 2014Article
- Hemophilia A: an ideal disease to correct in utero.Frontiers in pharmacology · 2014Review
- Generation of an optimized lentiviral vector encoding a high-expression factor VIII transgene for gene therapy of hemophilia A.Gene therapy · 2013Article
- Chemical chaperones improve protein secretion and rescue mutant factor VIII in mice with hemophilia A.PloS one · 2012Article
- Article
- Engineering Factor Viii for Hemophilia Gene Therapy.Journal of genetic syndromes & gene therapy · 2011Article
- Engineered Hematopoietic Stem Cells as Therapeutics for Hemophilia A.Journal of genetic syndromes & gene therapy · 2011Article
- Enhanced biosynthesis of coagulation factor VIII through diminished engagement of the unfolded protein response.The Journal of biological chemistry · 2011Article
- Lentiviral vector platform for production of bioengineered recombinant coagulation factor VIII.Molecular therapy : the journal of the American Society of Gene Therapy · 2011Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Successful gene therapy of hemophilia A depends on the sustained expression of therapeutic levels of factor VIII (fVIII). Because of mRNA instability, interactions with resident endoplasmic reticulum (ER) chaperones, and the requirement for carbohydrate-facilitated transport from the ER to the Golgi apparatus, fVIII is expressed at much lower levels from mammalian cells than other proteins of similar size and complexity. A number of bioengineered forms of B domain-deleted (BDD) human fVIII have been generated and shown to have enhanced expression. Previously, we demonstrated that recombinant BDD porcine fVIII exhibits high-level expression due to specific sequence elements that increase biosynthesis via enhanced posttranslational transit through the secretory pathway. In the current study, high-expression recombinant fVIII constructs were compared directly in order to determine the relative expression of the various bioengineered fVIII transgenes. The data demonstrate that BDD porcine fVIII expression is superior to that of any of the human fVIII variant constructs tested. Mean fVIII expression of 18 units/10(6) cells/24 hr was observed from HEK-293 cells expressing a single copy of the porcine fVIII transgene, which was 36- to 225-fold greater than that of any human fVIII transgene tested. Furthermore, greater than 10-fold higher expression was observed in human cells transduced with BDD porcine fVIII versus BDD human fVIII-encoding lentiviral vectors, even at low proviral copy numbers, supporting its use over other human fVIII variants in future hemophilia A gene therapy clinical trials.
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