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dc.contributor.authorSubang, Maria C.en_GB
dc.contributor.authorFatah, Rewasen_GB
dc.contributor.authorBright, Carlyen_GB
dc.contributor.authorBlanco, Patriciaen_GB
dc.contributor.authorBerenstein, Marianaen_GB
dc.contributor.authorWu, Yingen_GB
dc.contributor.authorPodhajcer, Osvaldo L.en_GB
dc.contributor.authorWinyard, Paul G.en_GB
dc.contributor.authorChernajovsky, Yutien_GB
dc.contributor.authorGould, Daviden_GB
dc.date.accessioned2012-12-17T13:27:12Zen_GB
dc.date.accessioned2013-03-20T17:09:04Z
dc.date.issued2012en_GB
dc.description.abstractThe aim of this study was to construct a promoter containing DNA motifs for an endogenous transcription factor associated with inflammation along with motifs for pharmacological regulation factors. We demonstrate in transfected cells that expression of a gene of interest is induced by hypoxic conditions or through pharmacological induction, and also show pharmacological repression. In vivo studies utilised electroporation of plasmid to mouse paws, a delivery method shown to be effective by bioluminescence imaging. For gene therapy, the promoter was used to drive expression of IL-1Ra in a paw inflammation model with therapeutic effect observed which was further enhanced when the promoter was additionally induced with a pharmacological activator. One of the most important observations from this study was that promoter induction by hypoxia or inflammation could be prevented by the pharmacological repressor in the absence of doxycycline. These studies demonstrate that hybrid promoters enable pharmacological adjustment to the pathophysiological level of gene expression and, importantly, that they allow termination of gene expression even in the presence of pathophysiological stimuli. © Springer-Verlag 2012.en_GB
dc.identifier.citationVol. 90 (4), pp. 401 - 411en_GB
dc.identifier.doi10.1007/s00109-011-0826-3en_GB
dc.identifier.urihttp://hdl.handle.net/10036/4091en_GB
dc.language.isoenen_GB
dc.publisherSpringeren_GB
dc.relation.urlhttp://dx.doi.org/10.1007/s00109-011-0826-3en_GB
dc.subjectGene therapyen_GB
dc.subjectRegulated gene expressionen_GB
dc.subjectHypoxiaen_GB
dc.subjectTetracyclineen_GB
dc.subjectInflammationen_GB
dc.subjectArthritisen_GB
dc.titleA novel hybrid promoter responsive to pathophysiological and pharmacological regulationen_GB
dc.typeArticleen_GB
dc.date.available2012-12-17T13:27:12Zen_GB
dc.date.available2013-03-20T17:09:04Z
dc.identifier.issn0946-2716en_GB
dc.descriptionCopyright © 2012 Springer. This article is published with open access at Springerlink.comen_GB
dc.identifier.journalJournal of Molecular Medicineen_GB


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