Engineering Modular Intracellular Protein Sensor-actuator Devices

Overview

Journal Nat Commun

Specialty Biology

Date 2018 May 16

PMID 29760420

Citations 21

Authors

Velia Siciliano

Breanna DiAndreth

Blandine Monel

Jacob Beal

Jin Huh

Kiera L Clayton

Liliana Wroblewska

AnneMarie McKeon

Bruce D Walker

Ron Weiss

Affiliations

Soon will be listed here.

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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