Abstract
The growing field of human synthetic biology has rapidly accelerated the development of programmable genetic systems that can control cellular phenotypes and function. As the scale of synthetic systems has increased, researchers have focused on identifying modular regulators that act at the levels of DNA, RNA, and protein to create synthetic control points at each level of gene expression. Expanding these assays to multiple cellular contexts has made it possible to both manipulate endogenous gene programs and create synthetic gene circuits that yield designer cell outputs. Here, we review recent advances in high-throughput human synthetic biology that have led to the development of multilevel tools for gene expression control. We highlight the development of synthetic gene programs that can both provide information on and manipulate cellular behavior and discuss the application of programmable genetic tools in therapeutic contexts to illuminate the power of these new biological approaches.