Abstract
Publisher Summary This chapter describes components that allow the tight regulation of gene expression in cell culture in response to a small molecule dimerizer. The system displays low or undetectable levels of transcription in the absence of dimerizer and high levels of dimerizer-dependent transcription. Target gene expression can be controlled accurately over a broad range and transcription can be turned off readily by the addition of monomeric ligand to the tissue culture medium. These properties appear to be robust; in particular, it is relatively easy to generate stable cell lines with low basal levels of transcription and high induction ratios of target gene expression. The incorporation of the bumped dimerizer and holed FK506-binding protein (FKBP) represent a significant advance in dimerizer-regulated transcription because it allows the use of small molecules that lack significant affinity for endogenous cellular FKBP. The flexibility of the dimerizer system and the fact that its protein components are derived exclusively from human protein sequences means that it is well placed for eventual use in regulating therapeutic gene expression in patients.
Published Version
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