Nucleic Acid Sensors
Our bodies are constantly under attack from foreign invaders like bacteria, viruses and fungi, and have evolved many layers of defence to combat these intruders and limit infection.
As part of these natural defences, every cell in our body has built-in alarms to watch for nucleic acids – genetic material including DNA and RNA – that don't belong there.
Normally, our own DNA stays neatly packaged inside the nucleus in the centre of our own cells, but sometimes during infection or disease it shows up somewhere it shouldn't, such as floating in the cytoplasm outside of the nucleus.
Also, pathogenic genetic material appears when people get an infection, which is equally unwelcome. In both cases, specialised proteins within our cells called nucleic acid sensors detect these DNA or RNA intruders almost instantly to raise the alarm.
Nucleic acid sensors include several Toll-like Receptors (TLRs), which sit within immune cells watching for the genetic fingerprints of invading viruses and bacteria. The moment a TLR spots something suspicious, it sets off a chain reaction that calls the immune system into action, helping the body fight off the infection.
The nucleic acid-sensing TLRs are TLR3, TLR7, TLR8 and TLR9 – with TLR7/8 being the targets of Noxopharm’s SOF-SKN™ drug candidate. Outside of TLRs, our cells also have a second line of nucleic acid sensors, including RIG-I, MDA5 and cGAS, which give the cell multiple and overlapping ways to spot an invader.
A macrophage cell showing TLRs on its surface
This defence system is a natural target for new medicines because it can be tuned in two directions – both up and down.
To tune it up, drug-like molecules that activate TLRs are already used as vaccine adjuvants, and are being explored in cancer immunotherapy to help the immune system better recognise and attack tumours.
Conversely, the system can be tuned down in instances when these same receptors misfire and react to the body's own DNA or RNA, helping to prevent chronic inflammation seen in autoimmune diseases where the body mistakenly attacks itself, such as in lupus.
Noxopharm and academic collaborator Professor Michael Gantier from Hudson Institute of Medical Research have published cutting-edge research redefining the paradigm for how these receptors operate in both healthy and disease states.
Noxopharm’s Sofra™ platform leverages this new understanding of these receptors, allowing the company to design potent synthetic biomimics of natural nucleic acids to engage and precisely tune these sensors, either amplifying or restraining them.
This unique and versatile approach is now enabling the development of treatments for inflammatory and autoimmune diseases, oncology and beyond – all built on one of biology's most fundamental defence mechanisms.
