Genetically-engineered bacteria could detect tumour DNA

The discovery was made using a new Cellular Assay for Targeted CRISPR-discriminated Horizontal gene transfer (CATCH), designed by scientists from the University of California San Diego and their colleagues in Australia. 

Their innovation, which detected cancer in the colons of mice, could pave the way for new biosensors capable of identifying various infections, cancers and other diseases.

In the past, bacteria have been used to carry out various diagnostic and therapeutic functions. However, the method has so far lacked the ability to identify specific DNA sequences and mutations outside of cells. 

“As we started on this project four years ago, we weren’t even sure if using bacteria as a sensor for mammalian DNA was even possible,” said Dr Jeff Hasty, a professor at the University of California San Diego. “The detection of gastrointestinal cancers and precancerous lesions is an attractive clinical opportunity to apply this invention.”

Tumours are known to disperse, or shed, their DNA into the environments surrounding them. Many technologies can analyse purified DNA in the lab, but these cannot detect DNA where it is released.

Under the CATCH strategy, the researchers engineered bacteria using CRISPR technology to test free-floating DNA sequences on a genomic level and compare those samples with predetermined cancer sequences. 

“Knowing that cell-free DNA can be mobilised as a signal or an input, we set out to engineer bacteria that would respond to tumour DNA at the time and place of disease detection,” said Dan Worthley, a gastroenterologist and cancer researcher with the Colonoscopy Clinic in Brisbane, Australia.

The bacteria selected for the study was Acinetobacter baylyi. It was engineered to identify DNA from KRAS, a gene that is mutated in many cancers.

They programmed the bacterium with a CRISPR system designed to discriminate mutant copies from normal copies of KRAS. This means that only bacteria that had taken up mutant forms of KRAS – as found in precancerous polyps and cancers, for example – would survive to signal or respond to the disease.

“It was incredible when I saw the bacteria that had taken up the tumour DNA under the microscope,” said Australian researcher Josephine Wright. “The mice with tumours grew green bacterial colonies that had acquired the ability to grow on antibiotic plates.”

The researchers are now adapting their bacteria biosensor strategy with new circuits and different types of bacteria for detecting and treating human cancers and infections.

“There’s a future where nobody needs to die of colorectal cancer,” believes Worthley. “We hope that this work will be useful to bioengineers, scientists and clinicians in pursuit of this goal.”

The scientists’ findings were published in the journal Science.