What is mRNA?
Messenger RNA (mRNA) is a single-stranded molecule that carries genetic instructions from the cell's nucleus to its ribosomes, where proteins are assembled. It is transcribed from DNA, translated into protein, and then rapidly degraded — a temporary message rather than a permanent record.
For background on where this process takes place inside cells, see our cells and organelles guide. The nucleus, ribosomes and cytoplasm all feature in the mRNA vaccine story.
The key breakthrough: modified nucleosides
For decades, attempts to use synthetic mRNA as a medicine failed because the immune system recognised it as foreign (a danger signal left over from viral defence mechanisms) and destroyed it before it could be translated. The mRNA also triggered dangerous inflammatory responses.
In 2005, Katalin Karikó and Drew Weissman at the University of Pennsylvania published a paper showing that replacing uridine — one of the four RNA nucleosides — with pseudouridine caused the immune system to ignore the mRNA. The modified mRNA could now enter cells, produce protein, and avoid destruction.
Combined with lipid nanoparticles (tiny fat droplets that protect mRNA and help it enter cells), this created a practical delivery platform. The same platform underlies the Pfizer-BioNTech and Moderna COVID-19 vaccines developed in 2020 — designed, tested and manufactured faster than any vaccine in history.
Personalised cancer vaccines
Every tumour accumulates unique mutations that produce abnormal proteins called neoantigens — molecular fingerprints not found on normal cells. mRNA technology allows a personalised vaccine to be designed for each patient's tumour, instructing their immune system to recognise and attack cells bearing those neoantigens.
In a 2023 Phase 2 trial, a personalised mRNA cancer vaccine from BioNTech and Moderna reduced the recurrence of high-risk melanoma by 44% compared with immunotherapy alone. The full results were published in Nature in 2023.
For the related gene-editing approach to cancer treatment, see our CRISPR gene editing article. For how the immune system is trained by the gut microbiome, see our gut microbiome article.
What comes next
Beyond cancer, active mRNA vaccine programmes include:
- Influenza — annual reformulation of mRNA flu vaccines could be faster and more precisely targeted than current egg-grown vaccines.
- HIV — mRNA vaccines encoding broadly neutralising antibodies are in Phase 1 trials.
- RSV and other respiratory viruses — Moderna's RSV mRNA vaccine was approved in 2024.
- Rare genetic diseases — replacing missing or defective proteins using periodic mRNA doses rather than permanent gene editing.