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Using Synthetic Biology to Engineer Living Cells That Interface with Programmable Materials
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Programmable protein circuits in living cells.

Xiaojing J Gao1, Lucy S Chong1, Matthew S Kim1

  • 1Howard Hughes Medical Institute, Division of Biology and Biological Engineering, Broad Center, California Institute of Technology, 1200 East California Boulevard, Pasadena, CA 91125, USA.

Science (New York, N.Y.)
|September 22, 2018
PubMed
Summary
This summary is machine-generated.

Engineered viral proteases form a modular system for synthetic biology, enabling complex cellular functions. This protein circuit engineering platform offers scalable biotechnological applications without genomic integration.

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Area of Science:

  • Synthetic Biology
  • Molecular Engineering
  • Mammalian Cell Engineering

Background:

  • Engineering cellular behaviors requires sophisticated synthetic circuits.
  • Composable protein-protein regulation systems are crucial for rational circuit design.
  • Viral proteases offer potential as modular protein components.

Purpose of the Study:

  • To develop a composable protein-protein regulation system for engineering cellular functions.
  • To demonstrate the utility of engineered viral proteases as modular circuit components.
  • To create a scalable platform for protein circuit engineering in mammalian cells.

Main Methods:

  • Engineered viral proteases were designed to function as orthogonal modular proteases (CHOMP).
  • Input proteases were engineered to dock with and cleave target proteases, inhibiting their function.
  • CHOMP components were assembled into regulatory cascades, logic gates, and signal-processing functions.

Main Results:

  • The CHOMP system successfully implemented diverse circuit-level functions in mammalian cells.
  • A rationally designed CHOMP circuit induced cell death in response to Ras oncogene activation.
  • CHOMP circuits can be encoded as single transcripts and delivered without genomic integration.

Conclusions:

  • Engineered viral proteases provide a versatile and composable platform for synthetic protein circuits.
  • The CHOMP system enables the creation of complex regulatory and signal-processing functions.
  • CHOMP offers a scalable approach for protein circuit engineering in biotechnology.