Modular antibody-based protein sensors in mammalian cells for in-vivo rewiring of cellular fate

The potential of synthetic networks to reshape cellular behavior relies on the ability of engineered circuits to sense and process endogenous information and implement robust responses to intracellular conditions. We engineered a modular platform for programmable sensing-actuation devices in mammalian cells upon detection of a target protein. The genetic device couples the ability of single chain fragment antibody to specifically bind a target protein with TEV (Tobacco Etch Virus) protease activity. We successfully developed a programmable sensing-actuation device for proteins associated with hepatitis C virus (HCV), human immunodeficiency virus (HIV) and Huntington disease. Moreover, we demonstrate selective cell killing with incorporation of a pro-apoptotic gene, proving that our device has the potential to rewire cell fate. Our results demonstrate the capability of a modular framework to be adapted to detect different cellular states, and to reprogram cellular function by sensing protein biomarkers, in mammalian cells.