Abstract
The tetracycline-controlled Tet-Off and Tet-On gene expression systems are used to regulate the activity of genes in eukaryotic cells in diverse settings, varying from basic biological research to biotechnology and gene therapy applications. These systems are based on regulatory elements that control the activity of the tetracycline-resistance operon in bacteria. The Tet-Off system allows silencing of gene expression by administration of tetracycline (Tc) or tetracycline-derivatives like doxycycline (dox), whereas the Tet-On system allows activation of gene expression by dox. Since the initial design and construction of the original Tet-system, these bacterium-derived systems have been significantly improved for their function in eukaryotic cells. We here review how a dox-controlled HIV-1 variant was designed and used to greatly improve the activity and dox-sensitivity of the rtTA transcriptional activator component of the Tet-On system. These optimized rtTA variants require less dox for activation, which will reduce side effects and allow gene control in tissues where a relatively low dox level can be reached, such as the brain.
Keywords: Tet-On system, Tet-Off system, Transcription regulation, Doxycycline, Gene expression, rtTA, tTA, TetR.
Current Gene Therapy
Title:Tet-On Systems For Doxycycline-inducible Gene Expression
Volume: 16 Issue: 3
Author(s): Atze T. Das, Liliane Tenenbaum and Ben Berkhout
Affiliation:
Keywords: Tet-On system, Tet-Off system, Transcription regulation, Doxycycline, Gene expression, rtTA, tTA, TetR.
Abstract: The tetracycline-controlled Tet-Off and Tet-On gene expression systems are used to regulate the activity of genes in eukaryotic cells in diverse settings, varying from basic biological research to biotechnology and gene therapy applications. These systems are based on regulatory elements that control the activity of the tetracycline-resistance operon in bacteria. The Tet-Off system allows silencing of gene expression by administration of tetracycline (Tc) or tetracycline-derivatives like doxycycline (dox), whereas the Tet-On system allows activation of gene expression by dox. Since the initial design and construction of the original Tet-system, these bacterium-derived systems have been significantly improved for their function in eukaryotic cells. We here review how a dox-controlled HIV-1 variant was designed and used to greatly improve the activity and dox-sensitivity of the rtTA transcriptional activator component of the Tet-On system. These optimized rtTA variants require less dox for activation, which will reduce side effects and allow gene control in tissues where a relatively low dox level can be reached, such as the brain.
Export Options
About this article
Cite this article as:
Das T. Atze, Tenenbaum Liliane and Berkhout Ben, Tet-On Systems For Doxycycline-inducible Gene Expression, Current Gene Therapy 2016; 16 (3) . https://dx.doi.org/10.2174/1566523216666160524144041
DOI https://dx.doi.org/10.2174/1566523216666160524144041 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
Call for Papers in Thematic Issues
Programmed Cell Death Genes in Oncology: Pioneering Therapeutic and Diagnostic Frontiers (BMS-CGT-2024-HT-45)
Programmed Cell Death (PCD) is recognized as a pivotal biological mechanism with far-reaching effects in the realm of cancer therapy. This complex process encompasses a variety of cell death modalities, including apoptosis, autophagic cell death, pyroptosis, and ferroptosis, each of which contributes to the intricate landscape of cancer development and ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Interrelation of Major Depression and Antidepressant Transcriptomics
Current Psychopharmacology Xanthones from Mangosteen Extracts as Natural Chemopreventive Agents: Potential Anticancer Drugs
Current Molecular Medicine Prion Diseases: Time for a Therapy ?
Current Medicinal Chemistry - Immunology, Endocrine & Metabolic Agents MAPKs and Their Inhibitors in Neuronal Differentiation
Current Enzyme Inhibition Embryonic Morphogenetic Field Induces Phenotypic Reversion in Cancer Cells. Review Article
Current Pharmaceutical Biotechnology Curcumin and Curcumin-like Molecules: From Spice to Drugs
Current Medicinal Chemistry Heteromerization of G Protein-Coupled Receptors: Relevance to Neurological Disorders and Neurotherapeutics
CNS & Neurological Disorders - Drug Targets Review: Recent Clinical Trials in Epigenetic Therapy
Reviews on Recent Clinical Trials The Interactions of the 5-HT3 Receptor with Quipazine-Like Arylpiperazine Ligands. The Journey Track at the End of the First Decade of the Third Millennium
Current Topics in Medicinal Chemistry Autism, Mitochondria and Polybrominated Diphenyl Ether Exposure
CNS & Neurological Disorders - Drug Targets Improvement of malignant pleural mesothelioma immunotherapy by epigenetic modulators
Current Topics in Medicinal Chemistry α7 Nicotinic Acetylcholine Receptor Mediated Neuroprotection in Parkinson’s Disease
Current Drug Targets Mangrove Plants as a Source of Bioactive Compounds: A Review
The Natural Products Journal Structure, Roles and Inhibitors of a Mitotic Protein Kinase Haspin
Current Medicinal Chemistry Genome-Wide Expression Analysis of Valproate Action: A Systems Level Synthesis
Current Psychopharmacology Is alpha-Synuclein Pathology a Target for Treatment of Neurodegenerative Disorders?
Current Alzheimer Research Target Genetic Abnormalities for the Treatment of Colon Cancer and Its Progression to Metastasis
Current Drug Targets Resveratrol and Cancer Treatment: Is Hormesis a Yet Unsolved Matter?
Current Pharmaceutical Design NPY Signalling Pathway in Bone Homeostasis: Y1 Receptor as a Potential Drug Target
Current Drug Targets Quinoline as a Privileged Scaffold in Cancer Drug Discovery
Current Medicinal Chemistry