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

S. D. Scott, B. Marples, J. H. Hendry, L. S. Lashford, M. J. Embleton, R. D. Hunter, A. Howell, G. P. Margison

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Ionising 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 P1 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.

Original languageEnglish (US)
Pages (from-to)1121-1125
Number of pages5
JournalGene Therapy
Volume7
Issue number13
DOIs
StatePublished - Jul 2000
Externally publishedYes

Keywords

  • CRE recombinase
  • Ganciclovir
  • HSVtk
  • Molecular switch
  • Radiation-responsive elements
  • Radiotherapy

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics

Fingerprint Dive into the research topics of 'A radiation-controlled molecular switch for use in gene therapy of cancer'. Together they form a unique fingerprint.

  • Cite this

    Scott, S. 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), 1121-1125. https://doi.org/10.1038/sj.gt.3301223