Reprogramming cellular behavior. with RNA controllers
responsive to endogenous proteins.
Culler SJ, Hoff KG, Smolke CD.
Division of Chemistry and Chemical Engineering, 1200 East
California Boulevard, MC 210-41, California Institute of Technology, Pasadena,
CA 91125, USA.
Synthetic genetic devices that interface with native cellular
pathways can be used to change natural networks to implement new forms of
control and behavior. The engineering of gene networks has been limited by an
inability to interface with native components. We describe a class of RNA
control devices that overcome these limitations by coupling increased abundance
of particular proteins to targeted gene expression events through the regulation
of alternative RNA splicing. We engineered RNA devices that detect signaling
through the nuclear factor κB and Wnt signaling pathways in human cells and
rewire these pathways to produce new behaviors, thereby linking disease markers
to noninvasive sensing and reprogrammed cellular fates. Our work provides a
genetic platform. that can build programmable sensing-actuation devices enabling
autonomous control over cellular behavior.