There is still a long way to go to treat cancer in real time, at the exact point in the body where the cancer cells are. But a US-Australian research team has taken a small step towards this: In mouse experiments, they use genetically modified bacteria as biosensors to detect colon cancer in the body. The team led by Susan Woods from the University of Adelaide and Jeff Hasty from the University of California in San Diego predicts the first step for later treatment in the journal “Science”.
A special ability of competent bacteria
In the process, the team relies on horizontal gene transfer: genes are transferred from one cell to another. However, not by multiplying the DNA and dividing the bacterial cells. Rather, the DNA is passed between unrelated cells. In this way, bacteria also absorb DNA sequences from their immediate environment, they are competent.
In the future we will diagnose and treat many diseases with cells, not drugs.
Dan Worthleygastroenterologist and cancer researcher
The researchers took advantage of this property of competent bacteria, because tumors also release fragments of genetic material into their environment. The researchers modified the bacterium Acinetobacter baylyi using Crispr/Cas gene scissors to contain long DNA sequences that match the DNA of the human cancer gene KRAS reflected. mutated KRAS-variants are often involved in the development of colon cancer, but also of many other tumors.
“When we started the project four years ago, it wasn’t even certain whether it was even possible to use bacteria as a sensor for mammalian DNA,” Hasty is quoted as saying in a statement from his university. The procedure, called Catch for Cellular Assay for Targeted Crispr-discriminated Horizontal gene transfer, aims to ensure that bacteria take up DNA directly and match the DNA sequences with those of certain cancer genes.
If the bacteria don’t have the cancer gene KRASG12D repel, they die off from an antibiotic that they produce themselves. However, if the gene is present, a gene for antibiotic resistance is activated and the microbes multiply: the signal that the cancer has been identified.
The team first tested this ability in cell cultures in the laboratory, then on artificial organ structures and finally in a mouse model. Mice were injected with colon cancer cells that developed around tumors in the colon. The sensor bacteria, which the animals received by enema, reliably recognized the intestinal tumor.
“Our technology is currently restricted to certain sequences, so cancer detection is based on hotspot mutations like KRASG12D limited,” the researchers write. Your method is not yet ready for clinical use.
Potential is there to treat even other diseases
First of all, you have to make it possible for the bacteria to be taken in through the mouth and then to multiply sufficiently in the digestive tract. In addition, the procedure must be able to keep up with current examination methods such as colonoscopy and, last but not least, be safe for people and the environment.
“Catch has the potential to detect colorectal cancer early with the goal of preventing more people from dying from this and other cancers,” said Woods. But you can also treat infectious diseases. “In the future, we will identify and treat many diseases using cells, not drugs,” said co-author Dan Worthley.
It is even conceivable to equip the bacterial biosensors with substances such as proteins, molecules or nanobodies, so that they could immediately release the corresponding active substance when a disease is detected.