Synthetic Regulatory Genomics

The genomics era has yielded high-quality genome assemblies, comprehensive atlases of biochemical signatures of gene regulation, and genetic associations for thousands of common human diseases and traits. These dramatic advances in observational approaches have not been matched by perturbational genetic tools to facilitate direct and systematic hypothesis testing. Enabled by advances in DNA synthesis and assembly, genome engineering tools, and genomic readouts, synthetic regulatory genomics now promises access to a new scale of genomic manipulation to study the function of cohesive genomic units. Synthetic regulatory genomics is distinguished by the breadth of the genetic manipulations and their divergence from the reference sequence. These new tools enable an expanded focus to encompass sufficiency in addition to necessity and to enable a new era of perturbation analysis.