Theranostic cells: emerging clinical applications of synthetic biology

McNerney, Monica P.; Doiron, Kailyn E.; Ng, Tai L.; Chang, Timothy Z.; Silver, Pamela A.

doi:10.1038/s41576-021-00383-3

Cited by 53 publications

(32 citation statements)

References 169 publications

(199 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Regarding the use of microbial biosensors, ensuring biosafety is another challenge. To this end, bacterial pathogenicity, survival, and the risk of mutation should be minimized and under strict control (McNerney et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, synthetic biology offers next-generation diagnostic strategies through the engineering of probiotic bacteria. Early successes of the synthetic biology approaches are in clinical trials targeting metabolic diseases and cancers (McNerney et al, 2021). These strategies have been reviewed (Song et al, 2019;Barra et al, 2020;Lazar and Tabor, 2021;McNerney et al, 2021), including the engineering of probiotics to produce synthetic metabolites and therapeutic proteins (Kang et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

“…Early successes of the synthetic biology approaches are in clinical trials targeting metabolic diseases and cancers (McNerney et al, 2021). These strategies have been reviewed (Song et al, 2019;Barra et al, 2020;Lazar and Tabor, 2021;McNerney et al, 2021), including the engineering of probiotics to produce synthetic metabolites and therapeutic proteins (Kang et al, 2020). Collectively, these technologies have enabled the sensing of tumors and the release of therapeutics (Chien et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The Future Potential of Biosensors to Investigate the Gut-Brain Axis

Wang

Childers

2022

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

The multifaceted and heterogeneous nature of depression presents challenges in pinpointing treatments. Among these contributions are the interconnections between the gut microbiome and neurological function termed the gut-brain axis. A diverse range of microbiome-produced metabolites interact with host signaling and metabolic pathways through this gut-brain axis relationship. Therefore, biosensor detection of gut metabolites offers the potential to quantify the microbiome’s contributions to depression. Herein we review synthetic biology strategies to detect signals that indicate gut-brain axis dysregulation that may contribute to depression. We also highlight future challenges in developing living diagnostics of microbiome conditions influencing depression.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Future Potential of Biosensors to Investigate the Gut-Brain Axis

Wang

Childers

2022

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

show abstract

“…Secreted, diffusible signals can be detected by synthetic receptors that activate expression upon ligand binding [73,74]. Receptors may be engineered into the cells of interest, or they may be engineered into theranostic cells that serve as 'cellular sentinels' [123]. Rather than using biochemical assays to detect secreted proteins and metabolites from a cell of interest, theranostic cells can be engineered with synthetic receptors for the secreted molecule for in situ detection.…”

Section: Validating Cells and Simplifying Readouts In High-complexity Multicellular Assaysmentioning

confidence: 99%

Synthetic gene circuits as tools for drug discovery

Beitz

Oakes

Galloway

2022

Trends in Biotechnology

View full text Add to dashboard Cite

Within mammalian systems, there exists enormous opportunity to use synthetic gene circuits to enhance phenotype-based drug discovery, to map the molecular origins of disease, and to validate therapeutics in complex cellular systems. While drug discovery has relied on marker staining and high-content imaging in cell-based assays, synthetic gene circuits expand the potential for precision and speed. Here we present a vision of how circuits can improve the speed and accuracy of drug discovery by enhancing the efficiency of hit triage, capturing disease-relevant dynamics in cell-based assays, and simplifying validation and readouts from organoids and microphysiological systems (MPS). By tracking events and cellular states across multiple length and time scales, circuits will transform how we decipher the causal link between molecular events and phenotypes to improve the selectivity and sensitivity of cell-based assays. Enhancing phenotypic drug discovery with synthetic biologyDevelopment of new drugs requires identification and optimization of functional molecules that often proceeds sequentially through high-throughput discovery screening, hit validation, hit expansion and optimization, and preclinical disease modeling (see Glossary) (Figure 1, Key figure)[1]. Target-based drug discovery (TDD) programs aim to identify drug candidates that modulate a defined biological target that is hypothesized to play a causal role in initiating or sustaining a disease. TDD programs offer precision by directly screening for drug candidate efficacy using purified molecular targets [2]. By contrast, phenotypic drug discovery (PDD) programs aim to identify drug candidates that modulate a physiologically-relevant biological system or cellular signaling pathway and screen for drug efficacy using cell-based assays [2]. Cell-based assays are target-agnostic and provide the opportunity to identify therapeutics that resolve diseaseassociated phenotypic deficits even when the disease etiology remains obscure and targets are undefined. Thus, PDD has recently received renewed interest for its potential to identify first-in-class drugs that act via a novel mechanism of action (MoA) as well as identify drugs for disease with complex or unknown etiology [1][2][3][4]. In order to identify drug candidates that translate to effective therapeutics in the clinic, PDD programs require cell-based assays that faithfully recapitulate and report on disease-relevant processes. To efficiently and effectively screen in phenotypic models, assay development for initial discovery screens must balance throughput with the ability to capture these disease processes [1]. As PDD probes a larger biological space than TDD to identify potential therapeutics, the number of hits from an initial discovery screen in a PDD program may be very large [2]. Following initial discovery screens, hit validation and triage are required to produce a small number of high-confidence candidates to proceed to the resource-intensive stages of hit expansion, compound optimization, and hig...

show abstract

“…A major advantage of MBSs is their ability to execute in situ tasks without the risk of compromising the surrounding biological systems. Moreover, with the power of synthetic biology, these organisms can adopt genetic circuitries that allow environmental signals to trigger the execution of programmed tasks (Cubillos-Ruiz et al, 2021;McNerney et al, 2021). This dynamic responsiveness allows for applications that are condition-sensitive, in other words, programmed responses that are modulated based on environmental inputs (Chen et al, 2016;Yin et al, 2017;Zheng et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Microbial Biocontainment Systems for Clinical, Agricultural, and Industrial Applications

Angles

Valle-Pérez

Hauser

et al. 2022

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

Many applications of synthetic biology require biological systems in engineered microbes to be delivered into diverse environments, such as for in situ bioremediation, biosensing, and applications in medicine and agriculture. To avoid harming the target system (whether that is a farm field or the human gut), such applications require microbial biocontainment systems (MBSs) that inhibit the proliferation of engineered microbes. In the past decade, diverse molecular strategies have been implemented to develop MBSs that tightly control the proliferation of engineered microbes; this has enabled medical, industrial, and agricultural applications in which biological processes can be executed in situ. The customization of MBSs also facilitate the integration of sensing modules for which different compounds can be produced and delivered upon changes in environmental conditions. These achievements have accelerated the generation of novel microbial systems capable of responding to external stimuli with limited interference from the environment. In this review, we provide an overview of the current approaches used for MBSs, with a specific focus on applications that have an immediate impact on multiple fields.

show abstract

Theranostic cells: emerging clinical applications of synthetic biology

Cited by 53 publications

References 169 publications

The Future Potential of Biosensors to Investigate the Gut-Brain Axis

The Future Potential of Biosensors to Investigate the Gut-Brain Axis

Synthetic gene circuits as tools for drug discovery

Microbial Biocontainment Systems for Clinical, Agricultural, and Industrial Applications

Contact Info

Product

Resources

About