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Nat Chem Biol. 2016 Feb;12(2):82-6. doi: 10.1038/nchembio.1979. Epub 2015 Dec 7.

'Deadman' and 'Passcode' microbial kill switches for bacterial containment.

Chan CT1,2,3, Lee JW1,2,3, Cameron DE1,2,3, Bashor CJ1,2,3, Collins JJ1,2,3,4,5,6.

Author information

1
Institute for Medical Engineering &Science, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
2
Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
3
Synthetic Biology Center, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
4
Harvard-MIT Program in Health Sciences and Technology, Cambridge, Massachusetts, USA.
5
Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
6
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts, USA.

Abstract

Biocontainment systems that couple environmental sensing with circuit-based control of cell viability could be used to prevent escape of genetically modified microbes into the environment. Here we present two engineered safeguard systems known as the 'Deadman' and 'Passcode' kill switches. The Deadman kill switch uses unbalanced reciprocal transcriptional repression to couple a specific input signal with cell survival. The Passcode kill switch uses a similar two-layered transcription design and incorporates hybrid LacI-GalR family transcription factors to provide diverse and complex environmental inputs to control circuit function. These synthetic gene circuits efficiently kill Escherichia coli and can be readily reprogrammed to change their environmental inputs, regulatory architecture and killing mechanism.

PMID:
26641934
PMCID:
PMC4718764
DOI:
10.1038/nchembio.1979
[Indexed for MEDLINE]
Free PMC Article

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