Engineering autonomous closed-loop designer cells for disease therapy

Synthetic biology has made it possible to engineer mammalian cells for on-demand delivery of therapeutic agents, providing therapeutic solutions for chronic or intractable diseases. Currently, most of the engineered therapeutic cells are regulated by the administration of exogenous inducers, but the need for repeated administration of these xenobiotics is problematic from the viewpoints of patients' compliance and quality of life, as well as possible side effects. Recently, synthetic biologists started to address these issues by constructing autonomous, closed-loop therapeutic cells, often referred to as designer cells. These cells are equipped with sensing modules that detect and link marker(s) of the target disease to signaling cascades that stimulate the secretion of specified therapeutic agents in a timely and quantitative manner, without the need of exogenous inducers. Here, we review recent work on designer cell engineering and their in vivo therapeutic applications, focusing on the molecular mechanisms and signaling pathways employed.