Texas A Researchers Use AI to Transform Caffeine into Molecular Off-Switch for Engineered Cells
Researchers at the Texas A&M Health Institute of Biosciences and Technology have developed a novel system called CODS (Caffeine-Operated Dissociation System) using AI-guided de novo protein design. This system leverages caffeine as a molecular 'pause button' for engineered cells. The study, published in the Journal of the American Chemical Society, describes how the team reprogrammed an existing caffeine-responsive module into a ligand-dependent dissociation system. The CODS system pairs a caffeine-binding protein with a synthetic mini-binder, which dissociates upon caffeine addition, effectively shutting down cellular functions. This innovation allows for precise control over engineered cells, demonstrated in various biological contexts, including gene circuits and CAR T cells. 
