Advances in medical technology are paving the way for the use of cells, rather than pills, in detecting, preventing, and treating diseases. This field of medicine, known as cellular or cell therapy, is already being used in certain clinical situations such as faecal microbial transplants for severe gastrointestinal infections and bone marrow transplants for blood cancer. A new study published in Science describes how bacteria can be engineered to detect cancer cells.
The study began with a presentation by synthetic biologist Rob Cooper, who was studying genes and gene transfer in bacteria. Genes are the basic units of genetic inheritance, and gene transfer is the process by which genes are passed from one cell to another. This can occur vertically, through reproduction, or horizontally, when DNA is passed between unrelated cells.
Horizontal gene transfer is common in the microbial world, with certain bacteria able to acquire genes from cell-free DNA in their environment. This process, known as natural competence, inspired the idea that bacteria could be engineered to detect cancer by taking up tumor DNA.
The researchers chose Acinetobacter baylyi, a naturally competent bacterium, as the experimental biosensor for detecting cancer. They modified its genome to contain DNA sequences that matched those found in a specific human cancer gene. These sequences acted as landing pads for tumor DNA, allowing it to integrate into the bacterial genome. The integration of tumor DNA activated other genes, including an antibiotic resistance gene, which served as a signal for cancer detection.
The researchers conducted a series of experiments using the biosensor and tumor cells. They successfully detected tumor DNA when it was presented to the biosensor in purified form or alongside living tumor cells. They also tested the biosensor in live mice with and without colorectal cancer, and it accurately discriminated between the two groups.
The researchers further engineered the biosensor to detect single base pair changes within tumor DNA, allowing for more precise detection and targeting of specific genes. This technology, called CATCH (cellular assay for targeted, CRISPR-discriminated horizontal gene transfer), shows promise for detecting a range of diseases, particularly infections and cancers.
However, further testing is needed before CATCH can be used in clinical settings. The researchers are working on increasing the efficiency of DNA detection, evaluating the biosensor’s performance compared to other diagnostic tests, and ensuring safety for patients and the environment.
The potential of cellular healthcare extends beyond disease detection. Biosensors can be programmed to respond to disease signals by delivering specific biological therapies directly to the affected area in real time. This combination of diagnosis and treatment holds great promise for the future of medicine.
The study was conducted by a team including Professor Jeff Hasty, Dr Rob Cooper, Associate Professor Susan Woods, and Dr Josephine Wright.
