Researchers have developed a clinically relevant bacterium which produces cancer drugs then self-destructs, releasing the drugs at the site of tumours.
The approach, developed by researchers at the University of California (UC) San Diego and the Massachusetts Institute of Technology (MIT), enables continual production and release of drugs at disease sites in mice while simultaneously limiting the size, over time, of the populations of bacteria engineered to produce the drugs.
The team of researchers, led by Jeff Hasty, a professor of bioengineering and biology, then transferred the bacterial therapy to their MIT collaborators for testing in an animal model of colorectal metastasis. The design of the therapy represents a culmination of four previous Nature papers from the UC San Diego group that describe the systematic development of engineered genetic clocks and synchronisation.
Prof Hasty said: “In synthetic biology, one goal of therapeutics is to target disease sites and minimise damage. We also wanted to deliver a significant therapeutic payload to the disease site.”
To achieve this, he and his team synchronised the bacteria to release bursts of known cancer drugs when a bacterial colony self-destructs within the tumour environment. Conventional chemotherapy cannot always reach a tumour’s inner regions, but bacteria can colonise there. Importantly, the researchers observed that the combination of chemotherapy and the gene products produced by the bacterial circuit consistently reduced tumour size.
The new study offers a therapeutic approach that minimises damage to surrounding cells.
The findings are published in the July 20 online issue of Nature.
“The new work by Jeff Hasty and team is a brilliant demonstration of how theory in synthetic biology can lead to clinically meaningful advances,” said Jim Collins, a professor at MIT.
Next possible steps include investigating the natural presence of bacteria in tumours and then engineering these bacteria for use in vivo and using multiple strains of bacteria to form a therapeutic community.