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

2015; Nature Portfolio; Volume: 12; Issue: 2 Linguagem: Inglês

10.1038/nchembio.1979

1552-4469

Clement T. Y. Chan, Jeong Wook Lee, D. Ewen Cameron, Caleb J. Bashor, James J. Collins,

RNA and protein synthesis mechanisms

Synthetic biology has expanded the availability of engineered bacterial systems for diverse applications and is now developing safeguards for their effective and secure use. The report of two synthetic gene circuit ‘kill switches’ provides new biocontainment mechanisms for engineered Escherichia coli. 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.