Extremely short, or tiny, fragments of RNA - working copies of our genetic code - play a critical role in keeping the immune system in check, preventing inflammation and the onset of autoimmune disease, according to an international team of researchers led by scientists from The Hudson Institute of Medical Research in collaboration with The Australian National University (ANU).
According to the research team, the findings could lead to the development of new treatments for common autoimmune conditions such as lupus, psoriasis, rheumatoid arthritis and more.
The research findings, published in Nature Immunology , builds on the Nobel prize winning discoveries of microRNA (2024) and siRNAs (2006). Except where the molecules detailed in those discoveries contain around 20 bases, the new findings have uncovered short RNA fragments as small as one to three bases.
Historically, these tiny RNA fragments (between one and three bases long) were thought to be biological waste, until now.
"Our discovery shows that selected RNA fragments of only one to three bases help protect our bodies against misfiring of the immune system which mistakenly attacks the body - leading to autoimmunity," Professor Michael Gantier from The Hudson Institute of Medical Research, said.
"That tells us that extremely short RNA fragments generated during RNA recycling have important anti-inflammatory functions that no one suspected.
"We discovered that very short RNA fragments can bind to sensors of our immune system and block their activation, preventing the onset of autoimmune disease.
"This is the shortest class of RNAs ever reported to have a biological function - around six times shorter than Nobel Prize winning microRNAs."
When you are infected by a virus, your immune system uses special sensors (called TLR7 and TLR8) to detect bits of viral RNA and trigger an early immune response.
But the body's own dying cells also release RNA fragments, yet those fragments don't trigger the immune system's same defensive response.
Co-author Professor Ben Corry from ANU said key to this work was understanding why the immune system responds to viral RNA but doesn't respond to our bodies' own RNA.
"To do this we had to explain where each kind of molecule binds to protein receptors using computational modelling on the supercomputers housed at ANU," Professor Corry said.
"We found that a tiny difference in the structure of some of your own RNA makes it bind differently to the receptors, turning off the immune system like a special 'off switch', unless a burst of foreign RNA is present.
"This prevents the body attacking its own cells, which causes autoimmune disease."
The international research team's findings recently progressed through their first clinical trial, thanks to Australian-based pharmaceutical company Noxopharm.
The Heracles trial successfully showed the safety of a topical cream containing these tiny RNAs, with the aim of treating skin lupus and other skin autoimmune conditions.
This is the first clinical use of Noxopharm's SOFRA platform, and the company is confident of its potential for treating a range of autoimmune conditions.
This research also involved scientists from Japan, the United Kingdom and the United States.
