Scientists from the University of California, San Diego, and their colleagues in Australia have developed bacteria that can detect the presence of tumour DNA in a living organism, ushering in a new era of technologically powerful biological sensors.
Presence of tumour DNA
Their discovery, which detected cancer in mouse colons, could pave the way for new biosensors capable of detecting infections, tumours, and other disorders.
Bacteria were previously engineered to perform a variety of diagnostic and therapeutic roles, but they lacked the ability to detect specific DNA sequences and mutations outside of cells.
The new “Cellular Assay for Targeted CRISPR-discriminated Horizontal Gene Transfer,” or “CATCH,” was created to accomplish exactly that.
“We weren’t even sure if using bacteria as a sensor for mammalian DNA was even possible four years ago,” said scientific team leader Jeff Hasty, a professor in the UC San Diego School of Biological Sciences and Jacobs School of Engineering.
“Detection of gastrointestinal cancers and precancerous lesions is a promising clinical application for this invention.”
Tumours are known to distribute, or shed, their DNA into their surrounding habitats.
Many technologies can analyse purified DNA in the lab, but they cannot identify DNA in the wild. Using CRISPR technology.
The researchers created bacteria to test free-floating DNA sequences on a genomic level and compare those samples to preset cancer sequences.
“Many bacteria can take up DNA from their environment, a skill known as natural competence,” said Rob Cooper, a scientist at UC San Diego’s Synthetic Biology Institute and the study’s co-first author.
Hasty, Cooper, and Australian Doctor
Hasty, Cooper, and Australian doctor Dan Worthley worked together to develop the concept of natural competence in relation to bacteria and colon cancer, which is the third highest cause of cancer-related death in the United States.
They began to consider the prospect of manipulating bacteria found in the colon as new biosensors that could be used inside the gut to detect DNA produced by colorectal tumours.
They concentrated on Acinetobacter baylyi, a bacterium in which Cooper discovered the components required for both DNA uptake and CRISPR analysis.
“Knowing that cell-free DNA can be mobilised as a signal, or an input, we set out to engineer bacteria that would respond to tumour DNA at the time and place of disease detection,” explained Worthley, a gastroenterologist and cancer researcher at Brisbane’s Colonoscopy Clinic.
The researchers conceived, produced, and tested Acinetobacter baylyi as a sensor for recognising DNA from KRAS, a gene that is altered in many malignancies, with Australian colleagues Susan Woods and Josephine Wright.
They used a CRISPR technique to instruct the bacterium to distinguish between mutant and non-mutated versions of KRAS.
This indicates that only bacteria that have acquired mutant forms of KRAS, such as those seen in precancerous polyps and malignancies, would be able to signal or respond to the disease.
The new study builds on prior concepts about horizontal gene transfer, a process employed by organisms to pass genetic material between themselves in a way that differs from standard parent-to-offspring genetic inheritance.
While horizontal gene transfer from bacteria to bacteria is well known, the researchers were able to apply this principle from mammalian tumours and human cells into bacteria.
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