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.
Our Solution
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.
