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TAXI/UAS: A molecular switch to control expression of genes in vivo

Human Gene Therapy, ISSN: 1043-0342, Vol: 7, Issue: 7, Page: 809-820
1996
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Article Description

Numerous therapies and biological questions could be addressed in mammals by the application of a molecular switch that would allow physicians and/or investigators to turn individual genes on or off during the lifetime of the organism. We have constructed such a switch, composed of three elements: (i) an inducible promoter that is normally absent from mammalian genomes; (ii) a receptor that, when it is bound to an inducer drug, specifically activates transcription from the inducible promoter; and (iii) inducer drugs, such as RU486, whose pharmacological properties in humans and several mammalian species including mouse have been well studied. The molecular switch is functional in transiently and stably transfected cells. Importantly, both the total output and the induction levels of the reporter gene can be finely tuned, with induction levels of over 100-fold being readily attained. Finally, we demonstrate that the molecular switch can be used to regulate a mouse transgene using a gene therapy paradigm. The specificity of the system suggests that it should be useful in the analysis of gene function in transgenic animals and in the design of strategies for human gene therapy.

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