The covid-19 pandemic saw the advent of a revolutionary technology: the first vaccines to be approved that contain messenger RNA (mRNA). The approach helped scientists create vaccines based on this genetic material in less than a year, turning the tide of the pandemic and shattering the previous four-year record set by the mumps vaccine.
Not only have these new vaccines saved millions of lives, they have also confirmed the potential of mRNA to transform treatments. Today, hundreds of trials for mRNA-based therapies are under way. “This is a technology that’s just starting to hit the market,” says at Weill Cornell Medicine in New York City.
mRNA vaccines might seem entirely new, but they were actually more than half a century in the making. In 1961, this genetic material was discovered and found to carry instructions for producing proteins in cells.
Advertisement
This raised an exciting possibility: we could use mRNA to get our cells to pump out proteins, so long as we know their genetic sequences. The trouble was that our immune system flags foreign mRNA as an intruder, rapidly destroying it before it can be translated into proteins.
But in 2005, and , both at the University of Pennsylvania, found a way to modify mRNA so it could slip past our defences, laying the groundwork for vaccines.
Most antiviral vaccines work by introducing a dead version of the pathogen or a protein from it into the body. This trains our immune system to recognise the virus as an invader so it can quickly identify and attack it in the future. Proteins for these vaccines must be made in living cells, though, which is expensive and time-intensive.
But mRNA vaccines provide cells with the genetic instructions to produce the protein themselves. “mRNA allows us to turn you into a little manufacturing powerhouse facility,” says at pharmaceutical company Moderna in Massachusetts. This rapidly accelerates the process of making vaccines. For instance, Moderna started testing its mRNA covid-19 vaccine in people just 66 days after the SARS-CoV-2 virus was sequenced.
Another reason why mRNA vaccines rose to the occasion with covid-19 is that drug companies already had systems in place for producing them. Before the pandemic, they were being tested for infections such as Zika, says Karikó. “So we were able to move with a lot of speed and confidence in the manufacturing platform,” says Bennett.
Another benefit is that they are adaptable. “Once you have the [protein] sequence, you can produce a vaccine,” says Salvatore. So if a virus mutates, manufacturers can tweak their vaccines.
The ones made by Moderna and Pfizer/BioNTech have already paved the way for an mRNA vaccine against respiratory syncytial virus, which is approved in the US, Canada, the European Union and Qatar. Many more mRNA-based interventions could be on the horizon. “There are around 300 mRNA clinical trials going on,” says Weissman. “Many are for vaccines, including [against] HIV, influenza, norovirus, C. difficile, malaria, tuberculosis and other pathogens.”
In June 2024, Moderna announced promising results from a final-stage trial of a for influenza and covid-19. This elicited higher immune responses against the viruses responsible than the licensed flu and covid-19 vaccines in people aged 50 and up. The firm aims to submit the data to the US Food and Drug Administration by the end of the year, says Bennett, noting that a dual vaccine should improve immunisation compliance.
Other conditions may also be treated with mRNA technology. For instance, a trial of a personalised skin cancer is scheduled to conclude in 2029. In an earlier trial, combining it with a standard cancer drug of the cancer spreading or the person dying by 65 per cent during the roughly one-year study period, compared with the drug alone.
Weissman and his colleagues are also investigating mRNA as a treatment for genetic conditions, such as sickle cell disease. The idea is to deliver gene-editing therapy by encoding it in mRNA, but the challenge is developing ways to deliver mRNA therapies to the part of the body we want to target, says Karikó.
While mRNA may take years to reach its full potential, Weissman believes it is halfway there. This is largely due to the covid-19 vaccines sparking interest and investment that have brought the tech closer to revamping medicine.
Read more in our special report about the five years since covid-19
