ArticleGene therapy2000
Development of synthetic promoters for radiation-mediated gene therapy.
Article in Gene therapy, 2000. 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, 79 citations in OpenAlex.
- Promoter considerations in the design of lentiviral vectors for use in treating lysosomal storage diseases.Molecular therapy. Methods & clinical development · 2022Review
- Functional Interfaces, Biological Pathways, and Regulations of Interferon-Related DNA Damage Resistance Signature (IRDS) Genes.Biomolecules · 2021Review
- Enhanced EJ Cell Killing of (125)I Radiation by Combining with Cytosine Deaminase Gene Therapy Regulated by Synthetic Radio-Responsive Promoter.Cancer biotherapy & radiopharmaceuticals · 2015Article
- Influential Factors and Synergies for Radiation-Gene Therapy on Cancer.Analytical cellular pathology (Amsterdam) · 2015Review
- Developments in the tools and methodologies of synthetic biology.Frontiers in bioengineering and biotechnology · 2014Review
- Regulation of gene expression in prostate cancer cells with an artificially constructed promoter responsive to radiation.Gene therapy · 2012Article
- HSV Recombinant Vectors for Gene Therapy.The open virology journal · 2010Article
- Radiation-inducible silencing of uPA and uPAR in vitro and in vivo in meningioma.International journal of oncology · 2010Article
- Suppression of cancer growth by nonviral gene therapy based on a novel reactive oxygen species-responsive promoter.Molecular therapy : the journal of the American Society of Gene Therapy · 2009Article
- Synergistic effect of 15-lipoxygenase 2 and radiation in killing head-and-neck cancer.Cancer gene therapy · 2008Article
- The radiation-inducible pE9 promoter driving inducible nitric oxide synthase radiosensitizes hypoxic tumour cells to radiation.Gene therapy · 2008Article
- Enhanced gene expression from retroviral vectors.BMC biotechnology · 2008Article
- Evaluation of a synthetic CArG promoter for nitric oxide synthase gene therapy of cancer.Gene therapy · 2005Article
- Replication-competent herpes simplex vectors: design and applications.Gene therapy · 2005Review
- Optimization of radiation controlled gene expression by adenoviral vectors in vitro.Cancer gene therapy · 2005Article
- Gene therapy vectors containing CArG elements from the Egr1 gene are activated by neutron irradiation, cisplatin and doxorubicin.Cancer gene therapy · 2005Article
- VP22-mediated intercellular transport for suicide gene therapy under oxic and hypoxic conditions.Gene therapy · 2005Article
- Current status of tumor radiogenic therapy.World journal of gastroenterology · 2005Review
- Inducible promoters for gene therapy of head and neck cancer: an in vitro study.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2004Article
- Novel therapeutic strategies in prostate cancer management using gene therapy in combination with radiation therapy.World journal of urology · 2003Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Exposure of cells to ionising radiation results in the activation of specific transcriptional control (CArG) elements within the early growth response 1 (Egr1) gene promoter, leading to increased gene expression. As part of a study investigating the potential use of these elements in radiation-controlled gene therapy vectors, we have incorporated their sequences into a synthetic gene promoter and assayed for the ability to induce expression of a downstream reporter gene following irradiation. In vector-transfected MCF-7 breast adenocarcinoma cells, the synthetic promoter was more effective than the wild-type Egr1 counterpart in up-regulating expression of the reporter gene after exposure to a single 5 Gy dose, and equally effective as the wild-type in U87-MG glioma cells. The level of gene expression achieved using the synthetic promoter was dependent on the inducing radiation dose for both U87-MG and MCF-7 cells, being maximal at 3 Gy and decreasing at 5 and 10 Gy. Furthermore, induction could be repeated by additional radiation treatments. The latter indicates that up-regulation should be additive during fractionated radiotherapy schedules. To demonstrate the potential clinical benefit of such an approach, the synthetic promoters were also shown to drive expression of the herpes simplex virus thymidine kinase gene, leading to enhanced cell killing in the presence of the prodrug ganciclovir (GCV) when compared with cells treated with radiation alone. Our results demonstrate that the synthetic promoter is responsive to low doses of ionising radiation and therefore isolated CArG elements function as radiation-mediated transcriptional enhancers outside their normal sequence context. The continued development and optimisation of such radiation-responsive synthetic promoters is expected to make a valuable contribution to the development of future radiation-responsive vectors for cancer gene therapy.
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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.