mRNA: The messenger molecule

Posted: 18th November 2021

Originally discovered in 1961, messenger RNA (mRNA) is now world-famous as our get-out-of-jail-free card to escaping a locked-down COVID world.

But what is this ‘messenger’ molecule? And why is it so important in driving ‘new’ vaccine technology?

“If we think of DNA as our library – stable and locked away deep inside our cells – then mRNA is like a photocopy of just a few pages of information from that library,” explains SVI’s Professor Carl Walkley. “It’s a copy of a tiny section of DNA with largely a single job: instructions for the part of the cell that creates proteins. Once the mRNA’s instructions are used, they literally self-destruct.”

It is this ability to provide detailed instructions for protein production and then disappear that has now been harnessed to give the world protection against COVID-19.

But mRNA’s characteristics as highly specialised and mobile for a long time saw it relegated to the sidelines of medical research.

“Because mRNA is inherently unstable, it was for decades viewed as too difficult and expensive to develop as a therapeutic product,” says Carl. “However, it turns out that being rapidly modifiable, short-lived and able to be manufactured quickly makes it perfect for use in vaccines.”

Key to the success of applying mRNA in vaccines was how to deliver it, intact, so a cell can use its instructions without the immune system being activated. Encasing it in droplets of fat, or lipids, and making it look like the cells’ own RNA tricks the body into accepting it into cells, so the mRNA can do its work.

“Now that we’ve harnessed it, the beauty of mRNA vaccine technology is that it is endlessly modifiable and highly specific,” says Dr Jacki Heraud-Farlow, Christine Martin Fellow in SVI’s Cancer and RNA Biology laboratory, which Carl leads.

“Once we have the genetic code for any new or variant virus, it will be possible to replicate a section of it in mRNA and quickly deploy this into a vaccine candidate, ready for trials. The makers of the current mRNA vaccines, for instance, have revealed that they made a prototype vaccine within days of the new coronavirus genome being published.”

But like many seemingly ‘wonder’ discoveries in science, mRNA has a long history attached to it and is not an overnight discovery. Multiple leaps and incremental pieces of fundamental and applied research done in labs across the globe, in the 60 years since mRNA was first discovered, add up to what we see in vaccines today.

SVI’s Cancer and RNA Biology team are internationally recognised for their work to understand the complexities of ribonucleic acid (RNA) – of which mRNA is just one form.

“RNA is fundamental to transcribing DNA’s instructions into the creation of proteins that build every part of our bodies,” says Carl. “Our research investigates a family of proteins that change the sequence of RNA. Part of the reason for these changes is to trick the body’s immune system so it doesn’t destroy its own RNA, because – ironically – many viruses are actually RNA molecules.”

“We are seeking to understand how cells know which RNA is their own – and therefore safe – and which RNA might be a danger to the cell, such as a virus. We are trying to understand how RNA stays under control in normal cells, and how those intricate processes go wrong in cancer cells and in rare autoimmune diseases. This knowledge will have multiple applications – better care for people with rare genetic diseases, and the development of more targeted and effective treatments for cancers.”

For more on the history of mRNA vaccines, see this article from Nature magazine.

For more information please see: Cancer & RNA biology