4.8 Review

Engineering living therapeutics with synthetic biology

Journal

NATURE REVIEWS DRUG DISCOVERY
Volume 20, Issue 12, Pages 941-960

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41573-021-00285-3

Keywords

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Funding

  1. US Department of Defense [W81XWH-17-1-0159, W81XWH-16-1-0565]
  2. National Institutes of Health [1RC2DK120535-01A1, 5-R33-AI121669-04]
  3. Natural Sciences and Engineering Research Council of Canada
  4. Defense Threat Reduction Agency [HDTRA1-14-1-0006]

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Cell-based therapeutics designed with synthetic biology is an emerging strategy in medicine, utilizing genetically engineered cells for precise therapeutic control and potential treatment of various diseases. Compared to traditional therapies, synthetic biology approaches offer greater flexibility, specificity, and predictability in combating human diseases.
The design of cell-based therapeutics with synthetic biology is a rapidly growing strategy in medicine for the development of effective treatments for a variety of diseases. This article discusses advances in synthetic biology approaches to programme living cells with therapeutic functions as well as challenges for their development. The steadfast advance of the synthetic biology field has enabled scientists to use genetically engineered cells, instead of small molecules or biologics, as the basis for the development of novel therapeutics. Cells endowed with synthetic gene circuits can control the localization, timing and dosage of therapeutic activities in response to specific disease biomarkers and thus represent a powerful new weapon in the fight against disease. Here, we conceptualize how synthetic biology approaches can be applied to programme living cells with therapeutic functions and discuss the advantages that they offer over conventional therapies in terms of flexibility, specificity and predictability, as well as challenges for their development. We present notable advances in the creation of engineered cells that harbour synthetic gene circuits capable of biological sensing and computation of signals derived from intracellular or extracellular biomarkers. We categorize and describe these developments based on the cell scaffold (human or microbial) and the site at which the engineered cell exerts its therapeutic function within its human host. The design of cell-based therapeutics with synthetic biology is a rapidly growing strategy in medicine that holds great promise for the development of effective treatments for a wide variety of human diseases.

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