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Published November 26, 2010 | Accepted Version + Supplemental Material
Journal Article Open

Reprogramming Cellular Behavior with RNA Controllers Responsive to Endogenous Proteins


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.

Additional Information

© 2011 American Association for the Advancement of Science. Received 11 May 2010; accepted 6 October 2010. We thank K. Hertel for providing the pHis-BIVT-MS2-RSp55 construct, M. Jensen for providing pCD19t-Tk-T2A-IL15op_epHIV7, L. J. Maher for providing pGAD24, and B. Stewart for laboratory assistance. This work was supported by the Caltech Joseph Jacobs Institute for Molecular Engineering for Medicine (grant to C.D.S.), the NIH (fellowship to K.G.H., grant to C.D.S.), the U.S. Department of Defense (grant to C.D.S.), the Alfred P. Sloan Foundation (fellowship to C.D.S.), and the Bill and Melinda Gates Foundation (grant to C.D.S.). The authors have filed for a patent related to this work.

Attached Files

Accepted Version - nihms322765.pdf

Supplemental Material - Culler.SOM.pdf


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