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Engineering a modular double-transmembrane synthetic receptor system for customizing cellular programs.

Jingru Zhou1, Qiangqiang Ge1, Dandan Wang1

  • 1Department of Laboratory Medicine, The First Affiliated Hospital of USTC, MOE Key Laboratory for Membraneless Organelles and Cellular Dynamics, Hefei National Center for Cross-disciplinary Sciences, Biomedical Sciences and Health Laboratory of Anhui Province, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230027, P.R. China.

Cell Reports
|April 12, 2023
PubMed
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Researchers developed a novel synthetic receptor system for engineered cells. This system enables precise control over cellular responses to disease signals, expanding therapeutic applications.

Keywords:
CP: Cell biologycell engineeringdouble-transmembrane helicespositive loopsynthetic receptorstranscriptional programs

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Area of Science:

  • Synthetic biology
  • Cell engineering
  • Biotechnology

Background:

  • Designer receptors allow engineered cells to detect and respond to specific physiological or disease states.
  • Expanding the therapeutic potential of engineered cells requires novel synthetic receptor strategies.

Purpose of the Study:

  • To develop a versatile synthetic receptor system for engineered cells with dual control and enhanced sensitivity.
  • To demonstrate the adaptability of this system to various extracellular protein signals and customized outputs.

Main Methods:

  • Designed a synthetic receptor system incorporating two transmembrane helices for signal transduction.
  • Integrated a sensor-actuator device with a positive feedback loop for signal amplification and minimal background noise.
  • Tested the system's response to specific protein inputs like interleukin-1 (IL-1), programmed death ligand 1 (PD-L1), and HER2.

Main Results:

  • The synthetic receptor system demonstrated sensitive detection of extracellular protein signals.
  • The system successfully responded to diverse inputs including IL-1, PD-L1, and HER2.
  • Customized outputs, such as fluorescence and interleukin-2 (IL-2), were effectively released.

Conclusions:

  • The developed synthetic receptor system offers robust signaling and broad applicability.
  • This system represents a valuable tool for cell engineering in both fundamental research and translational medicine.