Engineering microbial diagnostics and therapeutics with smart control

Amrofell, Matthew B.; Rottinghaus, Austin G.; Moon, Tae Seok

doi:10.1016/j.copbio.2020.05.006

Cited by 23 publications

(11 citation statements)

References 53 publications

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“…2 and Table 1). 25,27,28 Here, we describe the emerging advances of SB-inspired cell engineering approaches in diagnostics that may speed up data acquisition with improved sensitivity, specificity, real-time quantification, and accuracy at a substantially lower cost.…”

Section: Engineered Cells For Diagnosismentioning

confidence: 99%

Synthetic biology-inspired cell engineering in diagnosis, treatment and drug development

Zhao

Song

Xie

et al. 2023

Sig Transduct Target Ther

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The fast-developing synthetic biology (SB) has provided many genetic tools to reprogram and engineer cells for improved performance, novel functions, and diverse applications. Such cell engineering resources can play a critical role in the research and development of novel therapeutics. However, there are certain limitations and challenges in applying genetically engineered cells in clinical practice. This literature review updates the recent advances in biomedical applications, including diagnosis, treatment, and drug development, of SB-inspired cell engineering. It describes technologies and relevant examples in a clinical and experimental setup that may significantly impact the biomedicine field. At last, this review concludes the results with future directions to optimize the performances of synthetic gene circuits to regulate the therapeutic activities of cell-based tools in specific diseases.

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Section: Engineered Cells For Diagnosismentioning

confidence: 99%

Synthetic biology-inspired cell engineering in diagnosis, treatment and drug development

Zhao

Song

Xie

et al. 2023

Sig Transduct Target Ther

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“…In particular, AMTs could be programmed with such genetic circuits to sense disease biomarkers and deliver therapeutics with site and dose specificity. This on-demand drug release is an attractive attribute of AMTs that could potentially enable an entirely novel therapeutic paradigm, in which drugs are delivered by self-regulating microbial cells that adapt to the precise disease state of an individual patient. , Bacterial biosensors have also been explored as diagnostic tools to detect the presence of pathological biomarkers in clinical samples , as a cost-effective solution to point-of-care diagnosis. Recent work has also demonstrated the feasibility of implementing bacterial biosensors in ingestible chips to wirelessly report on biomarkers in the intestine .…”

Section: Introductionmentioning

confidence: 99%

Characterization of Eight Bacterial Biosensors for Microbial Diagnostic and Therapeutic Applications

2022

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The engineering of microbial cells to produce and secrete therapeutics directly in the human body, known as advanced microbial therapeutics, is an exciting alternative to current drug delivery routes. These living therapeutics can be engineered to sense disease biomarkers and, in response, deliver a therapeutic activity. This strategy allows for precise and self-regulating delivery of a therapeutic that adapts to the disease state of the individual patient. Numerous sensing systems have been characterized for use in prokaryotes, but a very limited number of advanced microbial therapeutics have incorporated such sensors. We characterized eight different sensors that respond to physiologically relevant conditions and molecules found in the human body in the probiotic strain Escherichia coli Nissle 1917. The resulting sensors were characterized under aerobic and anaerobic conditions and were demonstrated to be functional under gut-like conditions using the nematode Caenorhabditis elegans as an in vivo model. We show for the first time how a biosensor is able to detect in vivo the bile acid-like molecule Δ4 -dafachronic acid, a small molecule in C. elegans that regulates lifespan. Furthermore, we exemplify how bacterial sensors can be used to dynamically report on changes in the intestinal environment of C. elegans, by demonstrating the use of a biosensor able to detect changes in lactate concentrations in the gut lumen of individual C. elegans. The biosensors presented in this study allow for dynamic control of expression in vivo and represent a valuable tool in further developing advanced microbiome therapeutics.

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“…Various promoters were constructed responding to chemical or physical factors such as Isopropyl β-d-1-thiogalactopyranoside (IPTG) 11 , nisin 12 , NO 13 and temperature 14 . Although these designs have good regulatory ability in specific application background, the ability is still greatly restricted 15 . Because of the complex physiological changes, seldom diseases have proper regulatory sensors, which limited the flexibility and generality of this strategy.…”

Section: Introductionmentioning

confidence: 99%

Optogenetic operated probiotics to regulate host metabolism by mimicking enteroendocrine

Zhang

Ling

et al. 2021

Preprint

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The enteroendocrine system plays an important role in metabolism. The gut microbiome regulates enteroendocrine in an extensive way, arousing attention in biomedicine. However, conventional strategies of enteroendocrine regulation via gut microbiome are usually non-specific or imprecise. Here, an optogenetic operated probiotics system was developed combining synthetic biology and flexible electronics to achieve in situ controllable secretion to mimic enteroendocrine. Firstly, optogenetic engineered Lactococcus lactis (L. lactis) were administrated in the intestinal tract. A wearable optogenetic device was designed to control optical signals remotely. Then, L. lactis could secrete enteroendocrine hormone according to optical signals. As an example, optogenetic L. lactis could secrete glucagon-like peptide-1(GLP-1) under the control of the wearable optogenetic device. To improve the half-life of GLP-1 in vivo, the Fc domain from immunoglobulin was fused. Treated with this strategy, blood glucose, weight and other features were relatively well controlled in rats and mice models. Furthermore, up-conversion microcapsules were introduced to increase the excitation wavelength of the optogenetic system for better penetrability. This strategy has biomedical potential in metabolic diseases therapy by mimicking enteroendocrine.

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Engineering microbial diagnostics and therapeutics with smart control

Cited by 23 publications

References 53 publications

Synthetic biology-inspired cell engineering in diagnosis, treatment and drug development

Synthetic biology-inspired cell engineering in diagnosis, treatment and drug development

Characterization of Eight Bacterial Biosensors for Microbial Diagnostic and Therapeutic Applications

Optogenetic operated probiotics to regulate host metabolism by mimicking enteroendocrine

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