ArticleGene therapy2003
Doxycycline-regulated lentiviral vector system with a novel reverse transactivator rtTA2S-M2 shows a tight control of gene expression in vitro and in vivo.
Article in Gene therapy, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Dual Pathways of Human Immunodeficiency Virus Type 1 Envelope Glycoprotein Trafficking Modulate the Selective Exclusion of Uncleaved Oligomers from Virions.Journal of virology · 2021Article
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- An improved Tet-on system in microRNA overexpression and CRISPR/Cas9-mediated gene editing.Journal of animal science and biotechnology · 2019Article
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- Constitutive and Inducible Systems for Genetic In Vivo Modification of Mouse Hepatocytes Using Hydrodynamic Tail Vein Injection.Journal of visualized experiments : JoVE · 2018Article
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- Independence between pre-mRNA splicing and DNA methylation in an isogenic minigene resource.Nucleic acids research · 2017Article
- The retroviral vector family: something for everyone.Virus genes · 2017Review
- Electrophysiological Properties and Viability of Neonatal Rat Ventricular Myocyte Cultures with Inducible ChR2 Expression.Scientific reports · 2017Article
- Promoter Specificity and Efficacy in Conditional and Inducible Transgenic Targeting of Lung Macrophages.Frontiers in immunology · 2017Article
- Genetically engineered suicide gene in mesenchymal stem cells using a Tet-On system for anaplastic thyroid cancer.PloS one · 2017Article
- Tightly regulated 'all-in-one' lentiviral vectors for protection of human hematopoietic cells from anticancer chemotherapy.Gene therapy · 2015Article
- Conditional expression of the type 2 angiotensin II receptor in mesenchymal stem cells inhibits neointimal formation after arterial injury.Journal of cardiovascular translational research · 2014Article
- Neurotrophin 3 transduction augments remyelinating and immunomodulatory capacity of neural stem cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2014Article
- Novel tumor growth inhibition mechanism by cell cycle regulator cdk2ap1 involves antiangiogenesis modulation.Microvascular research · 2010Article
- Construction and application of an inducible system for homogenous expression levels in bulk cell lines.PloS one · 2009Article
- In vivo gene regulation using tetracycline-regulatable systems.Advanced drug delivery reviews · 2009Review
- Intronically encoded siRNAs improve dynamic range of mammalian gene regulation systems and toggle switch.Nucleic acids research · 2008Article
- Gene delivery by lentivirus vectors.Molecular biotechnology · 2007Review
- Synthetic tetracycline-inducible regulatory networks: computer-aided design of dynamic phenotypes.BMC systems biology · 2007Article
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Authors and funding
7 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Regulated expression of therapeutic genes is required for long-term gene therapy applications for many disorders. Here we describe a doxycycline (dox)-regulated lentiviral vector system consisting of two HIV-1-based self-inactivating viruses. One of the vectors is constitutively expressing a novel improved version of the tetracycline reverse transactivator rtTA2(S)-M2 and the other has a rtTA responsive promoter driving the expression of beta-galactosidase gene (lacZ). The rtTA2(S)-M2 has highly improved properties with respect to specificity, stability and inducibility. Functionality of the system by dox was confirmed after in vitro cotransduction of Chinese hamster ovary and human endothelial hybridoma (EAhy926) cells. Regulation of the system showed tight control of the gene expression. Dose dependence for dox was seen with concentrations that can be obtained in vivo with doses normally used in clinical practice. LacZ expression could be switched on/off during long-term (3 months) culturing of cotransduced cells. The system was next tested in vivo after cotransduction into rat brain and studying expression of the lacZ gene in dox-treated and control rats. Nested RT-PCR confirmed that the tight control of the gene expression was achieved in vivo. Also, X-gal staining showed positive cells in the dox-treated rats, but not in the controls 10 days after cotransduction with 4 days preceding treatment with dox. It is concluded that our doxycycline-regulated vector system shows significant potential for long-term gene therapy treatments.
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