Traceless Regulation of Genetic Circuitry

The advent of synthetic biology, enabling the construction of synthetic genetic circuitry with designed functionality, has has a revolutionary impact on medicine, agriculture, sustainable energy, and the industrial production of high-value compounds over the last few decades. Gene switches have an indispensable role as regulators of such systems. Despite the early introduction of chemically inducible switches to regulate genetic circuitry, 'traceless' physical cues (e.g., light, heat, sound, magnetism, electricity, and mechanical force) can provide greater specificity, higher spatiotemporal resolution, more flexible switching patterns, and better compatibility with bioelectronic interfaces, which is of particular significance given the rise of electrogenetics. Indeed, traceless gene switches are on a path to become universal biological control ports interfacing physiology with the electronic world. In this review, we discuss the impact, challenges, and prospects of physically inducible, traceless gene switches in the context of recent cutting-edge applications.