Deadly Disease Turns Friendly as Weapon Against Cancer

Scientists have shown that bacterium behind the lethal Anthrax disease, could provide a friendly ‘weapon’ against cancer by providing a solution for delivering drugs for a specific form of gene therapy.

Using genetic engineering, a team led by Dr Simon Richardson at the University of Greenwich has shown that the anthrax toxin’s ‘warhead’ can be replaced with a gene therapy drug. The toxin’s natural ability of successfully moving around the body is left in place and can be used to transport the drug to the inside of the cell, preventing it from being digested in the cell’s stomach.

“This is the first time a disarmed toxin has been used to deliver gene-modulating drugs directly to a specific compartment within the cell. We’ve achieved this without the use of so called helper molecules, such as large positively charged molecules like poly(L-lysine). This is important as while these positively charged molecules, known as polycations, can condense DNA and protect it from attack by enzymes before it reaches the target, they are also known to be toxic, break cell membranes and are sent quickly to the liver to be removed from the body. In this study we demonstrate that using disarmed toxins without a polycation is effective, at a cellular level," said Dr Richardson.

During the development of this technology, scientists used STFC’s ISIS Neutron and Muon Source to visualise the system they’d built at the molecular level. Neutron measurements enabled the scientists to see that the drug delivery molecules they had designed were behaving as they had predicted.

Lead scientist of the neutron study, Dr Paul Dyer from the University of Greenwich, said: "Understanding the nature of toxin pore biology, in particular how proteins transit through the pore, provides insights into novel drug delivery strategies and therapeutics to prevent Anthrax intoxication in animal and humans. We are currently using neutron reflectometry and scattering to evaluate this process in nanodiscs containing the anthrax pore.”

In further experiments at the ISIS Neutron and Muon Source, Dr Dyer is hoping to see how the ‘gate keeper’, a doughnut-shaped protein which lodges in the cell’s defence, opens the gate for the drug to pass through into the cell. Results from this project may not only impact on the use of gene therapies in the fight against cancer, but may also apply to food security and preventing the release of anthrax both accidentally and deliberately