Multidimensional Control of Cas9 by Evolved RNA Polymerase-Based Biosensors.

ABSTRACT: Systems to control Cas9 with spatial and temporal precision offer opportunities to decrease side effects, protect sensitive tissues, and create gene therapies that are only activated at defined times and places. Here, we present the design of new Cas9 controllers based on RNA polymerase (RNAP)-based biosensors that produce gRNAs, thereby regulating target knockout. After development and validation of a new abscisic acid-inducible biosensor to control Cas9, we lowered the background of the system using continuous evolution. To showcase the versatility of the approach, we designed biosensors that measure medically relevant protein-protein interactions to drive knockout. Finally, to test whether orthogonal RNAP biosensors could integrate multiple input signals to drive multiple gRNA-based out

SUBMITTER: Pu J 

PROVIDER: S-EPMC5828011 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature