Team Engineers Bacteria that Can Detect Tumor DNA

Scientists from the University of California San Diego have engineered bacteria that can detect the presence of tumor DNA in a live organism. Their innovation, which detected cancer in the colons of mice, could pave the way to new biosensors capable of identifying various infections, cancers and other diseases. The study was published in Science.

Bacteria previously have been designed to carry out various diagnostic and therapeutic functions, but lacked the ability to identify specific DNA sequences and mutations outside of cells. The new Cellular Assay for Targeted CRISPR-discriminated Horizontal gene transfer, or CATCH, was designed to do just that.

Tumors are known to shed their DNA into the environments surrounding them. Many technologies can analyze 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.

“Many bacteria can take up DNA from their environment, a skill known as natural competence,” said Rob Cooper, the study’s co-first author who along with colleagues collaborated on the idea of natural competence in relation to bacteria and colorectal cancer. They began to formulate the possibility of engineering bacteria, which are already prevalent in the colon, as new biosensors that could be deployed inside the gut to detect DNA released from colorectal tumors. They focused on Acinetobacter baylyi, a bacterium in which Cooper identified the elements necessary for both taking up DNA and using CRISPR to analyze it.

The team then designed, built, and tested Acinetobacter baylyi as a sensor for identifying DNA from KRAS, a gene that is mutated in many cancers. They programmed the bacterium with a CRISPR system designed to discriminate mutant 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.

The new research is based on previous ideas related to horizontal gene transfer, a technique used by organisms to move genetic material between one another in a manner distinct from traditional parent-to-offspring genetic inheritance. While horizontal gene transfer is widely known from bacteria to bacteria, the researchers achieved their goal of applying this concept from mammalian tumors and human cells into bacteria.

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.