New Route To On-Off Gene Control

A bacterial immune system component called CRISPR/Cas9 has been widely adopted in the past year for modifying genes and turning them on or off to study gene expression and develop new therapies. Timothy K. Lu and coworkers at MIT have now succeeded in both activating and repressing genes with the same Cas9 construct, just slightly modified by a customized guide RNA in each case to hit a different spot on a gene’s promoter (ACS Synth. Biol. 2013, DOI: 10.1021/sb400081r). The researchers note that the constructs are easier to design, synthesize, and validate than gene transcription control elements based on zinc finger proteins and transcription activator-like effectors and are more compact and versatile than CRISPR/Cas9 systems that turn genes on or off but not both. They also showed that their system can be used to turn synthetic gene promoters on and off in engineered yeast and human cells—a step toward creating synthetic circuits inside cells that could be used to detect or correct malfunctioning networks that cause disease.