Compositions for Activating and Silencing Gene Expression

Stanford researchers have developed an expanded catalog of compact transcription effector domains and fused them onto DNA binding domains to engineer synthetic transcription factors. These synthetic transcription factors perform targeted and tunable gene expression regulation in eukaryotic cells, with applications in gene and cell therapy, synthetic biology, and functional genomics. Previously, a limited number of effector domains were available for engineering synthetic transcription factors. In response, Bassik Lab and Bintu Lab researchers applied a high-throughput approach to discover and characterize effector domains at a 1000-fold larger scale than previous efforts. Their approach has enabled the discovery of hundreds of short effector domains (?80 amino acids; advantageous for delivery) that can upregulate or downregulate transcription in a targeted manner when fused onto a DNA binding domain.

Stage of Development – Research in vitro
The large, diverse domain collection expands the catalog of effectors that can be used to create synthetic transcription factors with new properties. Their systematic analysis of the effectors' sequence-function relationships provides a resource for further engineering compact tools for controlling gene expression, and refines predictive computational models of effector domain function.