4.8 Article

The evolution of synthetic receptor systems

Journal

NATURE CHEMICAL BIOLOGY
Volume 18, Issue 3, Pages 244-255

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41589-021-00926-z

Keywords

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Funding

  1. Indo-US Science & Technology Forum (IUSSTF)
  2. Department of Science & Technology (DST), Government of India
  3. National Science Foundation [DGE-1842165, CBET-2034495]
  4. National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (NIH) [1R01EB026510, EB021030-03]
  5. National Institute of General Medicine of the NIH [R35 GM138256]

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Researchers have repurposed natural receptors to engineer synthetic receptors that enable cells to detect and respond to their environments. By improving and integrating protein-based receptors and signal-processing components, customized functions and programming can be achieved.
Receptors enable cells to detect, process and respond to information about their environments. Over the past two decades, synthetic biologists have repurposed physical parts and concepts from natural receptors to engineer synthetic receptors. These technologies implement customized sense-and-respond programs that link a cell's interaction with extracellular and intracellular cues to user-defined responses. When combined with tools for information processing, these advances enable programming of sophisticated customized functions. In recent years, the library of synthetic receptors and their capabilities has substantially evolved-a term we employ here to mean systematic improvement and expansion. Here, we survey the existing mammalian synthetic biology toolkit of protein-based receptors and signal-processing components, highlighting efforts to evolve and integrate some of the foundational synthetic receptor systems. We then propose a generalized strategy for engineering and improving receptor systems to meet defined functional objectives called a 'metric-enabled approach for synthetic receptor engineering' (MEASRE).

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