A Brief Review on Engineering Synthetic Regulators for Bi-Directional Gene Expression Regulation

ABSTRACT: Since the advent of the first synthetic gene circuit, the field of gene circuits design has made great progress over the past several decades, bringing in feedback controllers, biomolecular neural networks, etc. The foundation of these circuits lies in their capability to precisely regulate gene expression in response to environmental cues. In this brief review, we focus on the constituent gene activation and repression regulatory parts, discuss their application and current progresses in bi-directional gene expression regulations, given the critical importance of such capability in ensuring a wide range of circuit properties, such as reference tracking, disturbance rejection, and system stability. We also discuss the integration of mathematical modeling in facilitating circuits design to complement the review. We anticipate more efforts to develop synthetic gene regulators that can repeatedly up- and down-regulate target gene expression dynamics in the future.