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

Autor: Scott, S D, Marples, B, Hendry, J H, Lashford, L S, Embleton, M J, Hunter, R D, Howell, A, Margison, G P
Předmět:
Zdroj: Gene Therapy; Jul2000, Vol. 7 Issue 13, p1121, 5p
Abstrakt: 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 Iox-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, HSVtk. 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index