Journal article
Engineering modular intracellular protein sensor-actuator devices
Nature communications, Vol.9(1), pp.1881-7
05/14/2018
DOI: 10.1038/s41467-018-03984-5
PMCID: PMC5951936
PMID: 29760420
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.
Details
- Title: Subtitle
- Engineering modular intracellular protein sensor-actuator devices
- Creators
- Velia Siciliano - Massachusetts Institute of TechnologyBreanna DiAndreth - Massachusetts Institute of TechnologyBlandine Monel - Ragon Institute of MGH, MIT and HarvardJacob Beal - RTXJin Huh - Massachusetts Institute of TechnologyKiera L. Clayton - Ragon Institute of MGH, MIT and HarvardLiliana Wroblewska - PfizerAnneMarie McKeon - Ragon Institute of MGH, MIT and HarvardBruce D. Walker - Ragon Institute of MGH, MIT and HarvardRon Weiss - Massachusetts Institute of Technology
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.9(1), pp.1881-7
- Publisher
- Springer Nature
- DOI
- 10.1038/s41467-018-03984-5
- PMID
- 29760420
- PMCID
- PMC5951936
- ISSN
- 2041-1723
- eISSN
- 2041-1723
- Number of pages
- 7
- Grant note
- R01CA207029 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) W911NF-11-2-0054 / DARPA; United States Department of Defense; Defense Advanced Research Projects Agency (DARPA) P50 GM098792 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Language
- English
- Date published
- 05/14/2018
- Academic Unit
- Electrical and Computer Engineering
- Record Identifier
- 9984627291302771
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