Engineering molecular circuits using synthetic biology in mammalian cells

Abstract

Synthetic biology has made significant leaps over the past decade, and it now enables rational and predictable reprogramming of cells to conduct complex physiological activities. The bases for cellular reprogramming are mainly genetic control components affecting gene expression. A huge variety of these modules, ranging from engineered fusion proteins regulating transcription to artificial RNA devices affecting translation, is available, and they often feature a highly modular scaffold. First endeavors to combine these modules have led to autoregulated expression systems and genetic cascades. Analogous to the rational engineering of electronic circuits, the existing repertoire of artificial regulatory elements has further enabled the ambitious reprogramming of cells to perform Boolean calculations or to mimic the oscillation of circadian clocks. Cells harboring synthetic gene circuits are not limited to cell culture, as they have been successfully implanted in animals to obtain tailor-made therapeutics that have made it possible to restore urea or glucose homeostasis as well as to offer an innovative approach to artificial insemination.