Scientific Background

Hudson Institute of Medical Research is a leading Australian medical research organisation recognised internationally for discovery science and translational research, and home to Australia’s largest group of inflammation and immunity scientists and clinicians.

The partnership with Noxopharm is founded on a breakthrough discovery made by Associate Professor Michael Gantier of the Hudson Institute, an expert in nucleic acids biology, and an international team of researchers.

To protect us against infections, our immune system relies on special immune sensors inside our cells that act like security guards. Two such sensors, called TLR7 and TLR8, selectively detect fragmented pieces of RNA that come from invading viruses or bacteria. Once these RNA fragments are detected, TLR7 and TLR8 sound the alarm, which leads to inflammation that, in turn, fights the infection.

Every day, billions of our cells quietly die and are replaced as part of our body’s natural housekeeping. This natural cell death also results in an abundance of RNA fragments. Curiously, these RNA fragments do not trigger the immune system in healthy people – and it is this fundamental question of why immune sensors such as TLR7 and TLR8 do not mistakenly sound the alarm from our own body’s RNA fragments that is at the heart of this discovery.

The team’s research discovered that some of our own RNA fragments carry a special chemical tag called 2′-O-methyl (2′-OMe). Critically, the team was able to demonstrate that these tagged RNA fragments bind in a different way to TLR7 and TLR8, effectively blocking their activation by other RNA fragments. Thus, this tag keeps the immune sensors in check, preventing false alarms by stopping them from overreacting to our own RNA fragments.

This discovery is critically important as it provides a new explanation for the cause of some autoimmune diseases. The importance of this protective mechanism is demonstrated in people with genetic mutations that prevent the binding of the tagged RNA to TLR7 and TLR8. These patients’ immune systems wrongly attack their own cells due to unchecked TLR7 and TLR8 activation, leading to chronic inflammation that drives autoimmunity.

The work outlined above has become the foundation of Noxopharm's Sofra technology platform, enabling the company to create leading-edge new drugs that mimic the tagged RNA and are intended to restore the balance to a misfiring immune system by using the same natural mechanisms that the body employs.