Colon noah picture Bacteria into colon Bacteria finds cancer
Bacteria detects cancer Bacteria secretes colour Poop is blue
Abstract
Plain text
Colorectal cancer is the second most deadly cancer worldwide. Current screening methods have low detection rates and result in frequent false positives, leading to missed diagnoses or unnecessary colonoscopies. We therefore created a user-friendly and easy self-test referred to as a living diagnostic. The bacterial strain Escherichia coli Nissle 1917 was designed to bind to tumour cells, detect two distinct cancer biomarkers, and secrete a coloured protein in the stool, hence the name Colourectal. Lactate serves as the first biomarker. We modelled and constructed a threshold-based circuit that uses this biomarker as an inducer resulting in the production of a signal protein at significantly elevated lactate levels. The second biomarker, matrix metalloproteinase 9, activates the colour of our signal protein. Only when both biomarkers are present will our coloured signal protein be observable in the stool. Additionally, we have implemented biosafety circuits to restrict to the colon, by creating a dependence on temperature and mucin. A third layer of biosafety allows removal of the bacterium when needed. Further, we have modelled persistence of our living diagnostic in the gut and used this to determine an optimal administration strategy. The detection of two different early cancer biomarkers and the three layers of biosafety, make Colourectal a safe and sensitive alternative to current colorectal cancer screening methods.

Colorectal cancer, sometimes called colon cancer, is the second deadliest cancer worldwide. Current screening methods have low detection rates and often result in false positives. This leads to missed diagnoses or unnecessary, invasive treatments. To solve this, we created an easy diagnostic tool called Colourectal. This is a bacterial strain that is designed to detect two distinct cancer indicators in the colon. A coloured protein will appear in the stool only if:

  • Lactate is detected at high levels and
  • Matrix Metalloproteinase 9 (MMP-9) activates the colour of our signal protein.

It is designed to only work in the colon, and it can be removed at any time. As a result, Colourectal has been designed to be safe to use as a self-test alternative to current screening methods.

2 million people got diagnosed with Colorectal cancer in 2020
Colorectal cancer was the second most deadly cancer in 2020
Early diagnosis is key to survival
Current treatment
Invitation of risk groups FIT biopsy test Positivty result colonoscopy
The current most used screening method for colorectal cancer is the Faecal Immunochemical Test (FIT). This test requires the user to take their own stool sample and send it to the laboratory for analysis. The FIT only detects blood in the stool, which causes a false positive rate of almost 30% [3].
Our Solution
Invitation of risk groups FIT biopsy test Positivty result colonoscopy
Our living diagnostic will replace the current diagnostic method with a simple and user-friendly test that detects two early cancer biomarkers on-site in the colon. Only when both biomarkers are present, the colour of the protein can be observed in the stool. Colourectal is easy and safe and can be administered at home as a self-test.
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