ArticleMolecular therapy : the journal of the American Society of Gene Therapy2010
Hyperactive sleeping beauty transposase enables persistent phenotypic correction in mice and a canine model for hemophilia B.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 77 citations in OpenAlex.
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- The FDA-Approved Drug Nelfinavir Inhibits Lytic Cell-Free but Not Cell-Associated Nonlytic Transmission of Human Adenovirus.Antimicrobial agents and chemotherapy · 2020Article
- Curative in vivo hematopoietic stem cell gene therapy of murine thalassemia using large regulatory elements.JCI insight · 2020Article
- Review
- Adenovirus vectors in hematopoietic stem cell genome editing.FEBS letters · 2019Review
- Enhanced Tropism of Species B1 Adenoviral-Based Vectors for Primary Human Airway Epithelial Cells.Molecular therapy. Methods & clinical development · 2019Article
- Viral Vector-Based Delivery of CRISPR/Cas9 and Donor DNA for Homology-Directed Repair in an In Vitro Model for Canine Hemophilia B.Molecular therapy. Nucleic acids · 2019Article
- Gene Therapy Leaves a Vicious Cycle.Frontiers in oncology · 2019Review
- Widespread airway distribution and short-term phenotypic correction of cystic fibrosis pigs following aerosol delivery of piggyBac/adenovirus.Nucleic acids research · 2018Article
- Human adenovirus type 17 from species D transduces endothelial cells and human CD46 is involved in cell entry.Scientific reports · 2018Article
- Constitutive and Inducible Systems for Genetic In Vivo Modification of Mouse Hepatocytes Using Hydrodynamic Tail Vein Injection.Journal of visualized experiments : JoVE · 2018Article
- Preclinical and clinical advances in transposon-based gene therapy.Bioscience reports · 2017Review
- Gene therapy with helper-dependent adenoviral vectors: lessons from studies in large animal models.Virus genes · 2017Review
- In Vivo Hematopoietic Stem Cell Transduction.Hematology/oncology clinics of North America · 2017Review
- Small-size recombinant adenoviral hexon protein fragments for the production of virus-type specific antibodies.Virology journal · 2017Article
- Prolonged Expression of Secreted Enzymes in Dogs After Liver-Directed Delivery of Sleeping Beauty Transposons: Implications for Non-Viral Gene Therapy of Systemic Disease.Human gene therapy · 2017Article
- A High-Capacity Adenoviral Hybrid Vector System Utilizing the Hyperactive Sleeping Beauty Transposase SB100X for Enhanced Integration.Molecular therapy. Nucleic acids · 2016Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Sleeping Beauty (SB) transposase enables somatic integration of exogenous DNA in mammalian cells, but potency as a gene transfer vector especially in large mammals has been lacking. Herein, we show that hyperactive transposase system delivered by high-capacity adenoviral vectors (HC-AdVs) can result in somatic integration of a canine factor IX (cFIX) expression-cassette in canine liver, facilitating stabilized transgene expression and persistent haemostatic correction of canine hemophilia B with negligible toxicity. We observed stabilized cFIX expression levels during rapid cell cycling in mice and phenotypic correction of the bleeding diathesis in hemophilia B dogs for up to 960 days. In contrast, systemic administration of an inactive transposase system resulted in rapid loss of transgene expression and transient phenotypic correction. Notably, in dogs a higher viral dose of the active SB transposase system resulted into transient phenotypic correction accompanied by transient increase of liver enzymes. Molecular analysis of liver samples revealed SB-mediated integration and provide evidence that transgene expression was derived mainly from integrated vector forms. Demonstrating that a viral vector system can deliver clinically relevant levels of a therapeutic protein in a large animal model of human disease paves a new path toward the possible cure of genetic diseases.
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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.