REMOTE CONTROL OF CELL FUNCTION USING TEMPERATURE AS AN INPUT

The increasing prevalence of RNA and cell-based therapies such as CAR-T, encapsulated cells, and gene therapies have generated a need to control cell function deep inside the body. However, traditional methods of deep-tissue cell actuation require injection of chemicals which can suffer from poor uptake, clearing, and a lack of spatio/temporal precision. Newer methods such as optogenetics suffer from the inability of light to penetrate tissue beyond a few millimeters. An attractive solution to overcome this challenge is using temperature as an inducer. Temperature can be regulated at distances of 10s of centimeters using safe and clinically approved technology such as focused ultrasound or hot/cold compresses. In this work, we develop a modular protein actuator that responds to small changes in temperature. We used this system to thermally control a wide variety of cellular functions including proteolysis, nuclear shuttling, Ras/Erk signaling, cell size, and cell death. Finally, we demonstrate that these tools can be used to non-invasively, locally activate cell death in cancer xenografts in mice.