Toward a world of theranostic medication: Programming biological sentinel systems for therapeutic intervention

Kojima, Ryosuke; Aubel, Dominique; Fussenegger, Martin

doi:10.1016/j.addr.2016.05.006

Cited by 30 publications

(24 citation statements)

References 74 publications

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“…Devices that endow mammalian cells with customised cell-contact sensing/response abilities can be used to create therapeutic cells for cancert reatment. [15] The best-known device in this class is the chimeric antigen receptor (CAR). CAR consists of a single-chain antibody (scFv) that recognises at arget antigen, and at ransmembrane and intracellular domain that triggers intracellular signalling and downstream gene expression in Tcells (Figure 2A,l eft).…”

Section: Controlling Gene Expression By Specific Cell Contactmentioning

confidence: 99%

Synthetic Biology: Engineering Mammalian Cells To Control Cell‐to‐Cell Communication at Will

Kojima

Fussenegger

2019

ChemBioChem

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Cell‐to‐cell communication plays a key role in the regulation of many natural biological processes. Recent advances in mammalian synthetic biology are making it possible to rationally engineer cell‐to‐cell communication for therapeutic and other purposes. Here, we review state‐of‐the‐art engineering principles to control cell‐to‐cell communication, focusing on communication between mammalian cells with diffusible factors (e.g., small molecules or exosomes) or direct cell contact, and on interkingdom communication between mammalian cells and bacteria. Potential applications include construction of artificial tissues able to perform complex computations, sophisticated cell‐based cancer therapies, use of mammalian cells as a new class of cargo delivery modality, development of design principles to control pattern formation of cell populations, and treatment of infectious diseases. We also discuss the challenges facing practical applications, and possible enabling technologies to overcome them.

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Section: Controlling Gene Expression By Specific Cell Contactmentioning

confidence: 99%

Synthetic Biology: Engineering Mammalian Cells To Control Cell‐to‐Cell Communication at Will

Kojima

Fussenegger

2019

ChemBioChem

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“…More recently, gene regulatory modules from Neurospora crassa were coupled to the Lac repressor to create a new orthogonal genetic tool, called LacQ, for regulating gene expression in mammalian cells [4]. Many of these transcription factor genetic circuits have been extensively reviewed elsewhere [128–137, 55, 138, 139, 47, 140, 59, 141–146, 66]. …”

Section: Targeting the Cell – Modules In Synthetic Biologymentioning

confidence: 99%

Bottom-up approaches in synthetic biology and biomaterials for tissue engineering applications

Weisenberger

Deans

2018

Journal of Industrial Microbiology and Biotechnology

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Synthetic biologists use engineering principles to design and construct genetic circuits for programming cells with novel functions. A bottom-up approach is commonly used to design and construct genetic circuits by piecing together functional modules that are capable of reprogramming cells with novel behavior. While genetic circuits control cell operations through the tight regulation of gene expression, a diverse array of environmental factors within the extracellular space also has a significant impact on cell behavior. This extracellular space offers an addition route for synthetic biologists to apply their engineering principles to program cell-responsive modules within the extracellular space using biomaterials. In this review, we discuss how taking a bottom-up approach to build genetic circuits using DNA modules can be applied to biomaterials for controlling cell behavior from the extracellular milieu. We suggest that, by collectively controlling intrinsic and extrinsic signals in synthetic biology and biomaterials, tissue engineering outcomes can be improved.

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“…It requires no special equipment, such as a confocal microscope or cell sorter. Much work in synthetic biology to date has focused on engineering diagnostic or therapeutic devices (Braff et al, 2016;Daeffler et al, 2017;Danino et al, 2015;Hwang et al, 2017;Kojima et al, 2016;Riglar et al, 2017;Slomovic et al, 2015). We hope that future work will expand the use of engineered organisms as research tools for exploring the complexities of in vivo settings and the dynamic actions of antibiotics and other therapeutic agents.…”

Section: No Antibioticsmentioning

confidence: 99%

Using Engineered Bacteria to Characterize Infection Dynamics and Antibiotic Effects In Vivo

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Pezone

et al. 2017

Cell Host & Microbe

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Synthetic biology has focused on engineering microbes to synthesize useful products or to serve as living diagnostics and therapeutics. Here we utilize a host-derived Escherichia coli strain engineered with a genetic toggle switch as a research tool to examine in vivo replicative states in a mouse model of chronic infection, and to compare in vivo and in vitro bacterial behavior. In contrast to the effect of antibiotics in vitro, we find that the fraction of actively dividing bacteria remains relatively high throughout the course of a chronic infection in vivo and increases in response to antibiotics. Moreover, the presence of non-dividing bacteria in vivo does not necessarily lead to an antibiotic-tolerant infection, in contrast to expectations from in vitro experiments. These results demonstrate the utility of engineered bacteria for querying pathogen behavior in vivo, and the importance of validating in vitro studies of antibiotic effects with in vivo models.

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Toward a world of theranostic medication: Programming biological sentinel systems for therapeutic intervention

Cited by 30 publications

References 74 publications

Synthetic Biology: Engineering Mammalian Cells To Control Cell‐to‐Cell Communication at Will

Synthetic Biology: Engineering Mammalian Cells To Control Cell‐to‐Cell Communication at Will

Bottom-up approaches in synthetic biology and biomaterials for tissue engineering applications

Using Engineered Bacteria to Characterize Infection Dynamics and Antibiotic Effects In Vivo

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