Engineering modular intracellular protein sensor-actuator devices
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s41467-018-03984-5.pdf
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Author(s)
Monel, Blandine
Beal, Jacob
Clayton, Kiera L
Wroblewska, Liliana
McKeon, AnneMarie
Walker, Bruce D.
Siciliano, Velia
DiAndreth, Breanna
Huh, Jin Hang
Weiss, Ron
Date Issued
May 2018
Journal
Nature Communications
Publisher
Nature Publishing Group
Citation
Siciliano, Velia et al. “Engineering Modular Intracellular Protein Sensor-Actuator Devices.” Nature Communications 9, 1 (May 2018): 1881 © 2018 The Author(s)
Version
Final published version
Abstract
Understanding and reshaping cellular behaviors with synthetic gene networks requires the ability to sense and respond to changes in the intracellular environment. Intracellular proteins are involved in almost all cellular processes, and thus can provide important information about changes in cellular conditions such as infections, mutations, or disease states. Here we report the design of a modular platform for intrabody-based protein sensing-Actuation devices with transcriptional output triggered by detection of intracellular proteins in mammalian cells. We demonstrate reporter activation response (fluorescence, apoptotic gene) to proteins involved in hepatitis C virus (HCV) infection, human immunodeficiency virus (HIV) infection, and Huntington's disease, and show sensor-based interference with HIV-1 downregulation of HLA-I in infected T cells. Our method provides a means to link varying cellular conditions with robust control of cellular behavior for scientific and therapeutic applications.
MIT Department
Institute for Medical Engineering and Science
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Synthetic Biology Center
Terms of Use
Creative Commons Attribution 4.0 International License
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DOI of Published Version
https://doi.org/10.1038/s41467-018-03984-5
