Engineering modular intracellular protein sensor-actuator devices.
Velia SicilianoBreanna DiAndrethBlandine MonelJacob BealJin HuhKiera L ClaytonLiliana WroblewskaAnneMarie McKeonBruce D WalkerRon WeissPublished in: Nature communications (2018)
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.
Keyphrases
- hepatitis c virus
- human immunodeficiency virus
- antiretroviral therapy
- hiv infected
- hiv aids
- hiv positive
- reactive oxygen species
- genome wide
- copy number
- gene expression
- cell proliferation
- oxidative stress
- protein protein
- transcription factor
- south africa
- amino acid
- small molecule
- single cell
- dna methylation
- social media