Bacteria Engineered to Detect Tumor DNA Could Seek and Destroy Gastrointestinal and Other Cancers

Tumors release their DNA into their surrounding environment, a phenomenon known as shedding. While various technologies can analyze purified DNA in laboratory settings, they fall short in detecting DNA in its released state. Although bacteria have been engineered for diverse diagnostic and therapeutic tasks, they cannot recognize specific DNA sequences and mutations outside of cells. Now, researchers have engineered bacteria that can identify tumor DNA in a live organism. This innovation, which successfully detected cancer in the colons of mice, has the potential for the creation of new biosensors to identify infections, cancers, and other diseases.

Under the new “Cellular Assay for Targeted CRISPR-discriminated Horizontal gene transfer,” or “CATCH,” strategy, scientists from the University of California San Diego (La Jolla, CA, USA) used CRISPR technology to engineer bacteria capable of assessing free-floating DNA sequences on a genomic level. These samples were then compared with predetermined cancerous sequences. The concept involved repurposing bacteria that are naturally present in the colon as biosensors, capable of detecting DNA released from colorectal tumors. The focus was on Acinetobacter baylyi, a bacterium in which the essential components for both acquiring DNA and utilizing CRISPR for analysis were identified.

Image: As seen in a dish, Acinetobacter baylyi (green) bacteria surround clumps of colorectal cancer cells (Photo courtesy of UC San Diego)

The researchers proceeded to design, construct, and assess Acinetobacter baylyi as a sensor for detecting DNA from the KRAS gene, which is frequently mutated in various cancers. They programmed the bacterium with a CRISPR system to differentiate between mutant and normal (non-mutated) variants of the KRAS gene. Consequently, only bacteria that had incorporated mutant KRAS forms, as present in precancerous growths and cancers, would survive to indicate or respond to the disease. This research builds upon the concept of horizontal gene transfer, a method by which genetic material is exchanged among organisms in a manner distinct from traditional genetic inheritance. While horizontal gene transfer is commonly observed between bacteria, the researchers successfully adapted this concept from mammalian tumors and human cells into bacteria.

The researchers are presently refining their bacteria-based biosensor strategy, exploring new circuits and various bacterial species for detecting and treating human cancers and infections. Researchers believe that in the future, cellular interventions will surpass traditional medicinal approaches. A living bacterium capable of detecting DNA within the gastrointestinal tract holds remarkable potential as a sentinel for identifying and combating gastrointestinal cancers, along with numerous other malignancies.

“There is so much potential to engineer bacteria to prevent colorectal cancer, a tumor that is immersed in a stream of bacteria, that could help, or hinder, its progression,” said researcher Susan Woods.

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