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

Scott, Simon D. and Marples, B. and Hendry, J.H. and Lashford, L.S. and Embleton, M.J. and Hunter, R.D. and Howell, A. and 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:https://doi.org/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)

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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
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: 05 Dec 2017 11:14 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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