Multi-input drug-controlled switches of mammalian gene expression based on engineered nuclear hormone receptors.

ABSTRACT: Protein-based switches that respond to different inputs to regulate cellular outputs, such as gene expression, are central to synthetic biology. For increased controllability, multi-input switches that integrate several cooperating and competing signals for the regulation of a shared output are of particular interest. The nuclear hormone receptor (NHR) superfamily offers promising starting points for engineering multi-input-controlled responses to clinically approved drugs. Starting from the VgEcR/RXR pair, we demonstrate that novel (multi-)drug regulation can be achieved by exchange of the ecdysone receptor (EcR) ligand binding domain (LBD) for other human NHR-derived LBDs. For responses activated to saturation by an agonist for the first LBD, we show that outputs can be boosted by an ago

SUBMITTER: Kretschmer S 

PROVIDER: S-EPMC9915577 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature