ArticleJournal of molecular medicine (Berlin, Germany)2006
An improved Tet-On regulatable FasL-adenovirus vector system for lung cancer therapy.
Article in Journal of molecular medicine (Berlin, Germany), 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 37 citations in OpenAlex.
- Immortalization Reversibility in the Context of Cell Therapy Biosafety.International journal of molecular sciences · 2023Review
- Cell Immortalization: In Vivo Molecular Bases and In Vitro Techniques for Obtention.Biotech (Basel (Switzerland)) · 2023Review
- A prospect of cell immortalization combined with matrix microenvironmental optimization strategy for tissue engineering and regeneration.Cell & bioscience · 2019Review
- Functional identification of optimized RNAi triggers using a massively parallel sensor assay.Molecular cell · 2011Article
- Tuning and controlling gene expression noise in synthetic gene networks.Nucleic acids research · 2010Article
- Intronically encoded siRNAs improve dynamic range of mammalian gene regulation systems and toggle switch.Nucleic acids research · 2008Article
- Turning the gene tap off; implications of regulating gene expression for cancer therapeutics.Molecular cancer therapeutics · 2008Review
- Anticancer activity of oncolytic adenovirus vector armed with IFN-alpha and ADP is enhanced by pharmacologically controlled expression of TRAIL.Cancer gene therapy · 2008Article
- Coxsackievirus B3 and adenovirus infections of cardiac cells are efficiently inhibited by vector-mediated RNA interference targeting their common receptor.Gene therapy · 2007Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene therapy is a new therapeutic approach for the treatment of human cancers. Gene expression systems that can be regulated by drugs have been developed to improve the safety and efficacy of therapeutic transgene delivery. One of the most promising systems is the tetracycline (Tet)-responsive system in the Tet-On configuration. A major problem of the Tet-On system if used in viral vectors is the high basal activity of the Tet response element (TRE) promoter leading to leaky expression of transgenes under uninduced conditions. We therefore evaluated novel TRE promoters for controlling gene expression in an adenovirus vector (AdV) Tet-On system and further investigated them for expression of the pro-apoptotic CD95/Fas ligand (FasL) in human epithelial carcinoma cell line (HeLa) and lung cancer cells. Plasmid-based reporter gene assays showed that modifications within the tetO (7) and minimal immediate early cytomegalovirus promoter (CMV)(min) sequence of the TRE promoter reduced its leakiness and led to a markedly improved regulatability by doxycycline. Among several TRE promoters tested, a new construct (TRE-Tight1) containing modifications of both the tetO (7) sequence and the CMV(min) showed 11-fold reduced leakiness and 1.5-fold increased absolute transgene expression levels after induction, as compared to the original TRE. Under induced conditions, a TRE-Tight1 promoter-dependent AdV expressing the pro-apoptotic CD95L/FasL induced apoptosis and cell lysis in HeLa cells as efficiently as an AdV containing the original TRE promoter. In contrast to the latter, however, the vector with the modified TRE promoter left cells totally unaffected in the absence of the inducer. Stringently regulated induction of apoptosis and cell death by TRE-Tight1-AdV was also demonstrated in three human lung cancer cell lines. These data show that the novel TRE-Tight1 promoter has a high potential for closely controlled and efficient expression of cytotoxic genes in AdV-based anti-cancer approaches.
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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.