By Irene Hsiao
Bryan Dickinson and his team have made strides in their investigation of RNA polymerase-based biosensors in two new papers in JACS and ACS Chemical Biology this September. In “Multidimensional Control of Cas9 by Evolved RNA Polymerase-Based Biosensors,” Dickinson, postdoc Jinyue Pu, and graduate student Kaitlin Kentala demonstrate a method for regulating the activity of Cas9, the RNA-guided protein used in the genome-editing technology CRISPR. Using RNAP biosensors that measure particular small molecules to induce the production of guide RNAs, the Dickinson group has developed a responsive, self-regulating on-off switch for Cas9 activity that promises greater precision in targeting and controlling gene therapies. In “RNA Polymerase Tags to Monitor Multidimensional Protein-Protein Interactions Reveal Pharmacological Engagement of Bcl-2 Proteins,” Dickinson and coworkers tag proteins of interest with N- or C-terminal split RNA polymerases. In the event of a protein-protein interaction, the resulting RNAP biosensor system encodes a unique RNA output, which can be used as an indicator and potentially engineered to produce a responsive therapeutic product. They demonstrate the use of their technology in a study of drug validation of Bcl-2 proteins, which induce and inhibit cell death. Together, these papers show that RNA polymerase biosensors can be used not only to gather information about chemistry in living cells, but also to respond to the conditions produced to drive therapeutic outcomes.