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Engineering modular intracellular protein sensor-actuator devices

Author

Listed:
  • Velia Siciliano

    (Istituto Italiano di Tecnologia
    Massachusetts Institute of Technology)

  • Breanna DiAndreth

    (Massachusetts Institute of Technology)

  • Blandine Monel

    (Massachusetts Institute of Technology, and Harvard University
    Howard Hughes Medical Institute)

  • Jacob Beal

    (Raytheon BBN Technologies)

  • Jin Huh

    (Massachusetts Institute of Technology)

  • Kiera L Clayton

    (Massachusetts Institute of Technology, and Harvard University
    Howard Hughes Medical Institute)

  • Liliana Wroblewska

    (Pfizer)

  • AnneMarie McKeon

    (Massachusetts Institute of Technology, and Harvard University
    Howard Hughes Medical Institute)

  • Bruce D. Walker

    (Massachusetts Institute of Technology, and Harvard University
    Howard Hughes Medical Institute
    Massachusetts Institute of Technology)

  • Ron Weiss

    (Massachusetts Institute of Technology)

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.

Suggested Citation

  • Velia Siciliano & Breanna DiAndreth & Blandine Monel & Jacob Beal & Jin Huh & Kiera L Clayton & Liliana Wroblewska & AnneMarie McKeon & Bruce D. Walker & Ron Weiss, 2018. "Engineering modular intracellular protein sensor-actuator devices," Nature Communications, Nature, vol. 9(1), pages 1-7, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-03984-5
    DOI: 10.1038/s41467-018-03984-5
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    Cited by:

    1. Alexander E. Vlahos & Jeewoo Kang & Carlos A. Aldrete & Ronghui Zhu & Lucy S. Chong & Michael B. Elowitz & Xiaojing J. Gao, 2022. "Protease-controlled secretion and display of intercellular signals," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    2. Nik Franko & Ana Palma Teixeira & Shuai Xue & Ghislaine Charpin-El Hamri & Martin Fussenegger, 2021. "Design of modular autoproteolytic gene switches responsive to anti-coronavirus drug candidates," Nature Communications, Nature, vol. 12(1), pages 1-12, December.
    3. Yage Ding & Cristina Tous & Jaehoon Choi & Jingyao Chen & Wilson W. Wong, 2024. "Orthogonal inducible control of Cas13 circuits enables programmable RNA regulation in mammalian cells," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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