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A radiation-controlled molecular switch for use in gene therapy of cancer

Scott, Simon D., Marples, B., Hendry, J.H., Lashford, L.S., Embleton, M.J., Hunter, R.D., Howell, A., Margison, G.P. (2000) A radiation-controlled molecular switch for use in gene therapy of cancer. Gene Therapy, 7 (13). pp. 1121-1125. ISSN 0969-7128. (doi:10.1038/sj.gt.3301223) (The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided)

The full text of this publication is not currently available from this repository. You may be able to access a copy if URLs are provided. (Contact us about this Publication)
Official URL
http://dx.doi.org/10.1038/sj.gt.3301223

Abstract

lonising radiation induces the expression of a number of radiation-responsive genes and there is current interest in exploiting this to regulate the expression of exogenous therapeutic genes in gene therapy strategies for cancer. However, the radiation-responsive promoters used in these approaches are often associated with low and transient levels of therapeutic gene expression. We describe here a novel radiation-triggered molecular switching device based on promoter elements from the radiation-responsive Egr-1 gene and the cre-LoxP site-specific recombination system of the PI bacteriophage. Using this system, a single, minimally toxic dose of radiation induced cre-mediated excision of a lox-P flanked stop cassette in a silenced expression vector and this resulted in amplified levels of CMV-promoter-driven expression of the exogenous tumour-sensitising gene, HSV-tk. This strategy could be used in combination with targeted delivery and tumour-specific promoters to elicit the tumour-targeted and prolonged expression of a variety of tumour-sensitising genes and provide an unprecedented level of control and tumour selectivity.

Item Type: Article
DOI/Identification number: 10.1038/sj.gt.3301223
Uncontrolled keywords: radiotherapy; radiation-responsive elements; molecular switch; CRE recombinase; HSVtk; ganciclovir
Subjects: R Medicine
R Medicine > RM Therapeutics. Pharmacology
Divisions: Faculties > Sciences > Medway School of Pharmacy
Depositing User: Simon Scott
Date Deposited: 03 Dec 2017 15:30 UTC
Last Modified: 29 May 2019 13:52 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/45897 (The current URI for this page, for reference purposes)
Scott, Simon D.: https://orcid.org/0000-0002-8290-0461
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