Engineering modular intracellular protein sensor-actuator devices

Nature Communications
Velia SicilianoRon Weiss

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.

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Citations

Sep 17, 2020·Nature Communications·Timothy FreiVelia Siciliano
Apr 3, 2019·Frontiers in Bioengineering and Biotechnology·Fabio CaliendoVelia Siciliano
Aug 10, 2019·BMC Biology·Aidan TinafarKeith Pardee
Jul 11, 2020·Advanced Biosystems·Michele DipaloFrancesco De Angelis
May 14, 2020·Advanced Biosystems·Hirohisa OhnoHirohide Saito
Apr 18, 2020·BioDrugs : Clinical Immunotherapeutics, Biopharmaceuticals and Gene Therapy·Congcong ZhangAndrea L J Marschall
Mar 30, 2021·Ageing Research Reviews·Rohan GuptaPravir Kumar
Apr 14, 2021·Cell·Zibo Chen, Michael B Elowitz
Jul 4, 2019·Nano Letters·Fabrizio A PennacchioFrancesca Santoro
Mar 20, 2019·ACS Synthetic Biology·Junmin WangCalin Belta

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Methods Mentioned

BETA
transfection
flow cytometry
Flow
flow-cytometry
Fluorescence
phage display
transfections
ELISA

Software Mentioned

Rosetta
FACSDiva8
FlowJo

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