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Related Experiment Video

Updated: Sep 11, 2025

Structured Approach to Colonoscopy Technique Optimization: A Single-Center Experience with Novice Endoscopists
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Multilayered safety framework for living diagnostics in the colon.

Sonia Mecacci1, Lucía Torregrosa-Barragán1, Enrique Asin-Garcia1,2

  • 1Laboratory of Systems and Synthetic Biology, Wageningen University & Research, Wageningen, Netherlands.

Frontiers in Systems Biology
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Summary

A novel living diagnostic tool, Colourectal, uses engineered bacteria to detect colorectal cancer biomarkers in stool. This synthetic biology approach enhances early cancer detection while prioritizing safety through multiple biological containment strategies.

Keywords:
auxotrophybiocontainmentbiosafetycolorectal cancerdiagnostic toolgenetic circuitsinducible kill switchessafe-by-design

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Area of Science:

  • Synthetic biology
  • Microbial diagnostics
  • Genetic engineering

Background:

  • Colorectal cancer is a leading cause of cancer death globally.
  • Current screening methods for colorectal cancer have limitations in detection rates and specificity.
  • There is a need for innovative diagnostic tools to improve early detection and patient outcomes.

Purpose of the Study:

  • To develop a novel living diagnostic tool for colorectal cancer using synthetic biology.
  • To engineer a strain of *Escherichia coli* Nissle 1917 for detecting cancer biomarkers and reporting results in stool.
  • To implement a multi-layered biosafety strategy for the safe *in vivo* application of genetically modified bacteria.

Main Methods:

  • Development of an engineered *Escherichia coli* Nissle 1917 strain.
  • Design of a synthetic chimeric receptor for mucin-dependent gene expression, confining bacteria to the colon.
  • Implementation of a temperature-sensitive kill switch for viability control outside the human body.
  • Integration of a CRISPR-Cas-mediated emergency kill switch for rapid bacterial inactivation.

Main Results:

  • The engineered bacteria successfully bind to tumor cells and detect two distinct colorectal cancer biomarkers.
  • A colored protein is secreted by the bacteria, making the diagnostic signal observable in stool.
  • The implemented biosafety measures include auxotrophy to mucin, a temperature-sensitive kill switch, and an emergency CRISPR-Cas kill switch.
  • The safe-by-design strategy ensures bacterial confinement to the colon, limits viability to the human body, and provides an emergency shutdown mechanism.

Conclusions:

  • The Colourectal project presents a viable synthetic biology approach for a living diagnostic tool for colorectal cancer.
  • The multi-layered biosafety strategy provides a robust framework for the safe development and potential future application of engineered microorganisms in human diagnostics.
  • This research contributes to advancing the field of microbial diagnostics and offers a promising direction for improving colorectal cancer screening.