Multiplexed Gene Expression Tuning with Orthogonal Synthetic Gene Circuits

[Image: see text] Understanding the individual and joint contribution of multiple protein levels toward a phenotype requires precise and tunable multigene expression control. Here we introduce a pair of mammalian synthetic gene circuits that linearly and orthogonally control the expression of two reporter genes in mammalian cells with low variability in response to chemical inducers introduced into the growth medium. These gene expression systems can be used to simultaneously probe the individual and joint effects of two gene product concentrations on a cellular phenotype in basic research or biomedical applications.