Engineering Microbial Living Therapeutics: The Synthetic Biology Toolbox

Microbes can be engineered to act like living therapeutics designed to perform specific actions in the human body. From fighting and preventing infections to eliminating tumors and treating metabolic disorders, engineered living systems are the next generation of therapeutics. In recent years, synth...

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Bibliographic Details
Published in:Trends in biotechnology (Regular ed.) Vol. 37; no. 1; pp. 100 - 115
Main Authors: Pedrolli, Danielle B., Ribeiro, Nathan V., Squizato, Patrick N., de Jesus, Victor N., Cozetto, Daniel A., Tuma, Rafael B., Gracindo, Amanda, Cesar, Mariana B., Freire, Paulo J.C., da Costa, Ana F.M., Lins, Milca R.C.R., Correa, Graciely G., Cerri, Marcel O.
Format: Journal Article
Language:English
Published: England Elsevier Ltd 01-01-2019
Elsevier Limited
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Summary:Microbes can be engineered to act like living therapeutics designed to perform specific actions in the human body. From fighting and preventing infections to eliminating tumors and treating metabolic disorders, engineered living systems are the next generation of therapeutics. In recent years, synthetic biologists have greatly expanded the genetic toolbox for microbial living therapeutics, adding sensors, regulators, memory circuits, delivery devices, and kill switches. These advances have paved the way for successful engineering of fully functional living therapeutics, with sensing, production, and biocontainment devices. However, some important tools are still missing from the box. In this review, we cover the most recent biological parts and approaches developed and describe the missing tools needed to build robust living therapeutics. Living therapeutics have been engineered to diagnose diseases and produce and deliver therapeutics in situ. These therapeutics can be equipped with devices for sensing inputs, controlling gene expression, building memory, and producing and delivering an active compound. Ingenious devices responding to stress, temperature, quorum-sensing signals, and other small molecules have been built to control the production and delivery of therapeutic molecules. To deal with biosafety, some living therapeutics carry biocontainment devices based on cell auxotrophy, temperature-sensitive regulators, and toxin/antitoxin counteraction. Recent advances in synthetic biology greatly expanded the toolbox for engineering living therapeutics; however, new parts are still needed to help synthetic biologists engineer more diverse and fully functional living therapeutics.
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ISSN:0167-7799
1879-3096
DOI:10.1016/j.tibtech.2018.09.005