TAXI UAS - A MOLECULAR SWITCH TO CONTROL EXPRESSION OF GENES IN-VIVO/

Numerous therapies and biological questions could be addressed in mamm als by the application of a molecular switch that would allow physicia ns 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 f rom mammalian genomes; (ii) a receptor that, when it is bound to an in ducer drug, specifically activates transcription from the inducible pr omoter; and (iii) inducer drugs, such as RU486, whose pharmacological properties in humans and several mammalian species including mouse hav e 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 in duction levels of over 100-fold being readily attained. Finally, we de monstrate that the molecular switch can be used to regulate a mouse tr ansgene using a gene therapy paradigm. The specificity of the system s uggests that it should be useful in the analysis of gene function in t ransgenic animals and in the design of strategies for human gene thera py.