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

2.50
Hdl Handle:
http://hdl.handle.net/10541/86680
Title:
A radiation-controlled molecular switch for use in gene therapy of cancer.
Authors:
Scott, S D; Marples, B; Hendry, Jolyon H; Lashford, Linda S; Embleton, M J; Hunter, Robin D; Howell, Anthony ( 0000-0002-3879-5991 ) ; Margison, Geoffrey P
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.
Affiliation:
Cancer Research Campaign Section of Genome Damage and Repair, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, UK.
Citation:
A radiation-controlled molecular switch for use in gene therapy of cancer. 2000, 7 (13):1121-5 Gene Ther.
Journal:
Gene Therapy
Issue Date:
Jul-2000
URI:
http://hdl.handle.net/10541/86680
PubMed ID:
10918478
Type:
Article
Language:
en
ISSN:
0969-7128
Appears in Collections:
All Christie Publications ; All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorScott, S Den
dc.contributor.authorMarples, Ben
dc.contributor.authorHendry, Jolyon Hen
dc.contributor.authorLashford, Linda Sen
dc.contributor.authorEmbleton, M Jen
dc.contributor.authorHunter, Robin Den
dc.contributor.authorHowell, Anthonyen
dc.contributor.authorMargison, Geoffrey Pen
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.en
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

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