G Protein–Coupled Receptors Revisited: Therapeutic Applications Inspired by Synthetic Biology

G protein–coupled receptors (GPCRs) mediate the majority of cellular responses to hormones and neurotransmitters within the human body. They have much potential in the emerging field of synthetic biology, which is the rational, systematic design of biological systems with desired functionality. The responsiveness of GPCRs to a plethora of endogenous and exogenous ligands and stimuli make them ideal sensory receptor modules of synthetic gene networks. Such networks can activate target gene expression in response to a specific stimulus. Additionally, because GPCRs are important pharmacological targets of various human diseases, genes encoding their protein/peptide ligands can also be incorporated as target genes of the response output elements of synthetic gene networks. This review aims to critically examine the potential role of GPCRs in constructing therapeutic synthetic gene networks and to discuss various challenges in utilizing GPCRs for synthetic biology applications.