Emerging mammalian gene switches for controlling implantable cell therapies

Engineered cell-based therapies have emerged as a new paradigm in modern medicine, with several engineered T cell therapies currently approved to treat blood cancers and many more in clinical development. Tremendous progress in synthetic biology over the past two decades has allowed us to program cells with sophisticated sense-and-response modules that can effectively control therapeutic functions. In this review, we highlight recent advances in mammalian synthetic gene switches, focusing on devices designed for therapeutic applications. Although many gene switches responding to endogenous or exogenous molecular signals have been developed, the focus is shifting towards achieving remote-controlled production of therapeutic effectors by stimulating implanted engineered cells with traceless physical signals, such as light, electrical signals, magnetic fields, heat or ultrasound.