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dc.contributor.authorScott, S D
dc.contributor.authorMarples, B
dc.contributor.authorHendry, Jolyon H
dc.contributor.authorLashford, Linda S
dc.contributor.authorEmbleton, M J
dc.contributor.authorHunter, Robin D
dc.contributor.authorHowell, Anthony
dc.contributor.authorMargison, Geoffrey P
dc.date.accessioned2009-11-23T11:28:58Z
dc.date.available2009-11-23T11:28:58Z
dc.date.issued2000-07
dc.identifier.citationA radiation-controlled molecular switch for use in gene therapy of cancer. 2000, 7 (13):1121-5 Gene Ther.en
dc.identifier.issn0969-7128
dc.identifier.pmid10918478
dc.identifier.urihttp://hdl.handle.net/10541/86680
dc.description.abstractIonising 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.
dc.language.isoenen
dc.subjectCanceren
dc.subjectCultured Tumour Cellsen
dc.subject.meshAntiviral Agents
dc.subject.meshCell Division
dc.subject.meshCytomegalovirus
dc.subject.meshFlow Cytometry
dc.subject.meshGanciclovir
dc.subject.meshGene Expression
dc.subject.meshGene Therapy
dc.subject.meshGene Transfer Techniques
dc.subject.meshGreen Fluorescent Proteins
dc.subject.meshHumans
dc.subject.meshIntegrases
dc.subject.meshLuminescent Proteins
dc.subject.meshNeoplasms
dc.subject.meshPromoter Regions, Genetic
dc.subject.meshSimplexvirus
dc.subject.meshThymidine Kinase
dc.subject.meshTumor Cells, Cultured
dc.subject.meshViral Proteins
dc.titleA radiation-controlled molecular switch for use in gene therapy of cancer.en
dc.typeArticleen
dc.contributor.departmentCancer Research Campaign Section of Genome Damage and Repair, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, UK.en
dc.identifier.journalGene Therapyen
html.description.abstractIonising 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.


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