ArticleGene therapy2003
Tetracycline-inducible transgene expression mediated by a single AAV vector.
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 38 papers.
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Who cites it
38 citing papers in PubMed, 106 citations in OpenAlex.
- Exploring AAV-Mediated Gene Therapy for Inner Ear Diseases: from Preclinical Success to Clinical Potential.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Enhancement of physiology via adaptive transcription.Pflugers Archiv : European journal of physiology · 2025Review
- A versatile in vivo platform for reversible control of transgene expression in adult tissues.Stem cell reports · 2025Article
- Designing AAV Vectors for Monitoring the Subtle Calcium Fluctuations of Inferior Olive NetworkFrontiers in cellular neuroscience · 2022Article
- Small scale adeno-associated virus-vector production for preclinical gene delivery based on chloroform precipitation.Neural regeneration research · 2022Article
- Adeno-associated viral (AAV) vector-mediated therapeutics for diabetic cardiomyopathy - current and future perspectives.Clinical science (London, England : 1979) · 2021Review
- AAV-mediated expression of 3TSR inhibits tumor and metastatic lesion development and extends survival in a murine model of epithelial ovarian carcinoma.Cancer gene therapy · 2020Article
- Developing biomarkers for neurodegenerative diseases using genetically-modified common marmoset models.Neural regeneration research · 2018Article
- Intracranial AAV-IFN-β gene therapy eliminates invasive xenograft glioblastoma and improves survival in orthotopic syngeneic murine model.Molecular oncology · 2017Article
- Antibody gene transfer with adeno-associated viral vectors as a method for HIV prevention.Immunological reviews · 2017Review
- Strategies for targeting primate neural circuits with viral vectors.Journal of neurophysiology · 2016Review
- A regulatable AAV vector mediating GDNF biological effects at clinically-approved sub-antimicrobial doxycycline doses.Molecular therapy. Methods & clinical development · 2016Article
- Gene delivery strategies to promote spinal cord repair.Biomarker insights · 2015Review
- A next step in adeno-associated virus-mediated gene therapy for neurological diseases: regulation and targeting.British journal of clinical pharmacology · 2013Review
- Adeno-associated Virus-mediated, Mifepristone-regulated Transgene Expression in the Brain.Molecular therapy. Nucleic acids · 2013Article
- An adeno-associated virus-based intracellular sensor of pathological nuclear factor-κB activation for disease-inducible gene transfer.PloS one · 2013Article
- Characterization of inducible models of Tay-Sachs and related disease.PLoS genetics · 2012Article
- Gene regulation systems for gene therapy applications in the central nervous system.Neurology research international · 2012Article
- Production and titering of recombinant adeno-associated viral vectors.Journal of visualized experiments : JoVE · 2011Article
- Development of a liver-specific Tet-on inducible system for AAV vectors and its application in the treatment of liver cancer.Molecular therapy : the journal of the American Society of Gene Therapy · 2011Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Regulated gene delivery systems are usually made of two elements: an inducible promoter and a transactivator. In order to optimize gene delivery and regulation, a single viral vector ensuring adequate stoichiometry of the two elements is required. However, efficient regulation is hampered by interferences between the inducible promoter and (i) the promoter used to express the transactivator and/or (ii) promoter/enhancer elements present in the viral vector backbone. We describe a single AAV vector in which transcription of both the reverse tetracycline transactivator (rtTA) and the transgene is initiated from a bidirectional tetracycline-responsive promoter and terminated at bidirectional SV40 polyadenylation sites flanking both ITRs. Up to 50-fold induction of gene expression in human tumor cell lines and 100-fold in primary cultures of rat Schwann cells was demonstrated. In addition an 80-fold induction in vivo in the rat brain has been obtained. In vitro, the autoregulatory vector exhibits an induced expression level superior to that obtained using the constitutive CMV promoter. Although extinction of the transgene after removal of tetracycline was rapid (less than 3 days), inducibility after addition of tetracycline was slow (about 14 days). This kinetics is suitable for therapeutic gene expression in slowly progressive diseases while allowing rapid switch-off in case of undesirable effects. As compared to previously described autoregulatory tet-repressible (tetOFF) AAV vectors, the tet-inducible (tetON) vector prevents chronic antibiotic administration in the uninduced state.
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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.