Engineering modular intracellular protein sensor-actuator devices

Velia Siciliano (), Breanna DiAndreth, Blandine Monel, Jacob Beal, Jin Huh, Kiera L Clayton, Liliana Wroblewska, AnneMarie McKeon, Bruce D. Walker and Ron Weiss ()
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Velia Siciliano: Istituto Italiano di Tecnologia
Breanna DiAndreth: Massachusetts Institute of Technology
Blandine Monel: Massachusetts Institute of Technology, and Harvard University
Jacob Beal: Raytheon BBN Technologies
Jin Huh: Massachusetts Institute of Technology
Kiera L Clayton: Massachusetts Institute of Technology, and Harvard University
Liliana Wroblewska: Pfizer
AnneMarie McKeon: Massachusetts Institute of Technology, and Harvard University
Bruce D. Walker: Massachusetts Institute of Technology, and Harvard University
Ron Weiss: Massachusetts Institute of Technology

Nature Communications, 2018, vol. 9, issue 1, 1-7

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-03984-5

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