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SynNotch-Programmed Macrophages for Cancerous Cell Detection and Sensing.

Tao Wang1, Cia-Hin Lau1, Naian Wang1

  • 1Department of Biology, College of Science, Shantou University, 515063 Shantou, Guangdong, China.

ACS Sensors
|November 4, 2024
PubMed
Summary

Engineered macrophages using Synthetic Notch (synNotch) receptors can detect cancer cells. This novel biosensor detects human chorionic gonadotropin (HCGB5) in urine for early cancer diagnosis.

Keywords:
CRISPR/DxPOCTcell sensorextracellular ligandsgenetic circuitsignal conductorsynthetic biology

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Area of Science:

  • Synthetic biology
  • Cellular engineering
  • Biomedical diagnostics

Background:

  • Synthetic Notch (synNotch) receptors enable engineered cells to respond to external signals by activating specific genetic programs.
  • Current cancer detection methods can be invasive or lack sensitivity, necessitating novel diagnostic approaches.

Purpose of the Study:

  • To develop a cell-based in vivo sensor for detecting cancerous cells using engineered macrophages.
  • To leverage the synNotch system for sensing cancer-specific ligands and triggering a detectable output.

Main Methods:

  • Macrophages were engineered with synNotch receptors to detect cancer cell ligands.
  • Upon ligand binding, synNotch activation led to the nuclear release of a transcriptional activator.
  • This activator induced downstream gene expression, specifically human chorionic gonadotropin (HCGB5) in macrophages.

Main Results:

  • Engineered macrophages successfully detected breast cancer cells expressing artificial EGFP ligands.
  • HCGB5 expression in macrophages was induced only in the presence of cancer cells.
  • Extracellular HCGB5 levels were directly proportional to the number of detected cancer cells.

Conclusions:

  • Demonstrated the feasibility of synNotch-programmed macrophages as a cancer cell sensor.
  • The system shows potential for non-invasive, urine-based cancer detection via HCGB5.
  • Further optimization could lead to point-of-care and home self-testing cancer diagnostics.