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

Chan, Ching-Kit; Lee, Jeong Wook; Cameron, D. Ewen; Bashor, Caleb J.; Collins, James J.

doi:10.1038/nchembio.1979

Cited by 290 publications

(288 citation statements)

References 46 publications

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“…The toggle switch uses two mutually repressing genes, effectively forming a positive feedback circuit, which leads to a bistable system that can switch between two possible states under suitable stimulation [24]. The toggle switch has been employed in several applications, such as in microbial kill switches for bacterial containment [25] and in detection/ recording devices for living diagnostics [26]. The repressilator, instead, uses three genes mutually repressing each other in a loop, effectively forming a negative feedback system with substantial phase lag along the loop, leading to a genetic oscillator [27].…”

Section: From Parts To Modulesmentioning

confidence: 99%

Control theory meets synthetic biology

Vecchio

Qian

2016

J. R. Soc. Interface.

239

191

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The past several years have witnessed an increased presence of control theoretic concepts in synthetic biology. This review presents an organized summary of how these control design concepts have been applied to tackle a variety of problems faced when building synthetic biomolecular circuits in living cells. In particular, we describe success stories that demonstrate how simple or more elaborate control design methods can be used to make the behaviour of synthetic genetic circuits within a single cell or across a cell population more reliable, predictable and robust to perturbations. The description especially highlights technical challenges that uniquely arise from the need to implement control designs within a new hardware setting, along with implemented or proposed solutions. Some engineering solutions employing complex feedback control schemes are also described, which, however, still require a deeper theoretical analysis of stability, performance and robustness properties. Overall, this paper should help synthetic biologists become familiar with feedback control concepts as they can be used in their application area. At the same time, it should provide some domain knowledge to control theorists who wish to enter the rising and exciting field of synthetic biology.

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Section: From Parts To Modulesmentioning

confidence: 99%

Control theory meets synthetic biology

Vecchio

Qian

2016

J. R. Soc. Interface.

239

191

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“…To combat this, engineered safeguard mechanisms have been developed to prevent unintended proliferation of engineered bacteria by killing bacteria that escape from spatial confinement [109] or by controlling the death or survival of engineered bacteria through specific chemical cues [110]. …”

Section: Treatmentsmentioning

confidence: 99%

Quantitative and synthetic biology approaches to combat bacterial pathogens

Bethke

Wang

et al. 2017

Current Opinion in Biomedical Engineering

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Antibiotic resistance is one of the biggest threats to public health. The rapid emergence of resistant bacterial pathogens endangers the efficacy of current antibiotics and has led to increasing mortality and economic burden. This crisis calls for more rapid and accurate diagnosis to detect and identify pathogens, as well as to characterize their response to antibiotics. Building on this foundation, treatment options also need to be improved to use current antibiotics more effectively and develop alternative strategies that complement the use of antibiotics. We here review recent developments in diagnosis and treatment of bacterial pathogens with a focus on quantitative biology and synthetic biology approaches.

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“…In the absence of aTc, this single-layer switch achieved an escape frequency of approximately equal to 2.4 × 10 −6 . Most recently, the “DEADMAN” and “PASSCODE” switches employed EcoRI as a cell-killing toxin without coexpression of the inhibitor, as their bistability multiple reinforcing layers enabled the tight control of EcoRI expression 31 .…”

Section: Strategy 3: Self-destroyingmentioning

confidence: 99%

Recent advances in synthetic biosafety

Simon

Ellington

2016

F1000Res

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Synthetically engineered organisms hold promise for a broad range of medical, environmental, and industrial applications. Organisms can potentially be designed, for example, for the inexpensive and environmentally benign synthesis of pharmaceuticals and industrial chemicals, for the cleanup of environmental pollutants, and potentially even for biomedical applications such as the targeting of specific diseases or tissues. However, the use of synthetically engineered organisms comes with several reasonable safety concerns, one of which is that the organisms or their genes could escape their intended habitats and cause environmental disruption. Here we review key recent developments in this emerging field of synthetic biocontainment and discuss further developments that might be necessary for the widespread use of synthetic organisms. Specifically, we discuss the history and modern development of three strategies for the containment of synthetic microbes: addiction to an exogenously supplied ligand; self-killing outside of a designated environment; and self-destroying encoded DNA circuitry outside of a designated environment.

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

Cited by 290 publications

References 46 publications

Control theory meets synthetic biology

Control theory meets synthetic biology

Quantitative and synthetic biology approaches to combat bacterial pathogens

Recent advances in synthetic biosafety

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