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Related Experiment Video

Updated: Feb 23, 2026

Mimicking the Function of Signaling Proteins: Toward Artificial Signal Transduction Therapy
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Engineering Synthetic Signaling Pathways with Programmable dCas9-Based Chimeric Receptors.

Toni A Baeumler1, Ahmed Ashour Ahmed2, Tudor A Fulga1

  • 1Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK.

Cell Reports
|September 14, 2017
PubMed
Summary

Researchers developed a new synthetic receptor platform using CRISPR/Cas9 (dCas9) technology. This dCas9-synR system allows designer cells to sense signals and control gene expression for advanced cellular engineering.

Keywords:
CRISPRGPCRRTKchimeric receptorsdCas9-VP64dCas9-synRgenome engineeringsplit Cas9synthetic receptorstranscriptional programs

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Area of Science:

  • Synthetic biology
  • Molecular and cellular biology
  • Biotechnology

Background:

  • Synthetic receptors are crucial for engineering cells to perform specific functions.
  • Current limitations exist in the programmability and adaptability of synthetic receptors.

Purpose of the Study:

  • To develop a novel, modular synthetic receptor platform based on nuclease-deficient CRISPR/Cas9 (dCas9).
  • To demonstrate the adaptability and functionality of this platform for cellular engineering applications.

Main Methods:

  • Engineered chimeric receptors integrating a dCas9 signal transduction module with native ectodomain scaffolds.
  • Tested receptor performance for OFF/ON state transitions and dose-dependent activation.
  • Programmed receptors to link disease markers with multi-gene expression circuits.

Main Results:

  • The dCas9 synthetic receptor (dCas9-synR) architecture was successfully adapted to various scaffolds.
  • Receptors exhibited stringent OFF/ON state transitions and dose-dependent activation.
  • Demonstrated programming of disease markers to control therapeutically relevant gene circuits.

Conclusions:

  • The modular dCas9-synR platform offers a generalizable blueprint for next-generation synthetic receptors.
  • This technology enables the creation of designer cells with complex, customizable functions.
  • Advances cellular engineering by providing a versatile tool for signal transduction and gene regulation.