Scientists have taken inspiration from nature to engineer a bacteria that can detect gastrointestinal cancers and precancerous lesions in animal models.
The international collaboration between researchers from the University of California San Diego (UCSD), South Australian Health and Medical Research Institute (SAHMRI) and University of Adelaide modified Acinetobacter baylyi to sense DNA released by colorectal tumours, which floats freely outside of the cancer within the body.
Drawing on bacteria’s ability to obtain new genetic information by interacting with other species and their environment – known as horizontal gene transfer – the group modified A. baylyi using CRISPR to sense, align with and integrate the colorectal cancer-promoting gene KRAS into its own DNA.
The researchers were then able to read a signal from the bacteria to identify its interaction with cancerous KRAS.
The system has been labelled CATCH (Cellular Assay of Target CRISPR-discriminated horizontal gene transfer), with the results of its test in animal models published in Science. Although it’s a long way from human trials, researchers are excited by the outcomes.
“We weren’t even sure if using bacteria as a sensor for mammalian DNA was even possible,” says Professor Jeff Hasty, UCSD’s co-senior author on the research. “The detection of gastrointestinal cancers and precancerous lesions is an attractive clinical opportunity to apply this invention.”
The upside suggested by the study is that DNA fragments of potential cancer don’t need to be isolated and purified to confirm the presence of disease.
But while colorectal cancer was targeted in this study, the project’s future may lie elsewhere.
Biomedical scientist Susan Woods, one of SAHMRI’s co-senior authors on the study who is also based at the Adelaide Medical School, suggests CATCH’s ultimate use might be in sensing out other disease-causing pathogens.
“Detecting cancer is quite difficult because there’re so many different changes that you could possibly be looking for,” Woods tells Cosmos. “So you’d need a sensor that was specific for each change. We’re probably not going to be able to cover all the genotypes of cancer.
“What might be a better use is actually looking for a pathogen. We know, for some bacteria, there’s a particular DNA change that causes a fairly innocuous bacteria to become a pathogen. We could find that quite readily.”
While the first application of the CATCH system shows promise, there’s a long way to go before it makes its way to a human clinical trial.
A. baylyi is a soil bacterium, so applying CATCH to a human-adapted species is an important next step. So too, where horizontal gene transfer is involved, is considering the safety impacts for use in trials and limiting a modified bacterium’s environmental distribution.
“Understanding how DNA moves around different organisms: we have to think carefully about what happens and check that we don’t get anything happening that we don’t want to happen,” Woods says.