The use of mRNA vaccines to tackle Covid-19 marks the start of a new era of medicine

Within the gloom of Covid-19 lies a glimmer of medical innovation. In December 2020, two vaccines – one jointly developed by Pfizer and BioNTech, another developed by Moderna – became the first to receive approval for Covid-19. These were no ordinary vaccines: they were ‘messenger RNA’ or ‘mRNA’ vaccines. The first to be used in the human body, they may augur well for a new era in medicine.

All vaccines work by teaching the body to recognise and destroy infectious agents such as viruses and bacteria. Conventional vaccines typically train the immune system by delivering weakened or inactivated forms of these viruses or bacteria into the body. This encourages the immune system to produce antibodies that can tackle those germs. Messenger RNA vaccines skip the first step, instead handing the body instructions to manufacture a portion of a protein, in this case known as a ‘spike protein’. This spike protein is the same as that found on the surface of a virus. The body recognises that the protein doesn’t belong and so begins building an immune response and making antibodies. If the actual virus enters the body later on, it’s ready to produce the correct antibodies.  

The potential for mRNA-based medicines has long been recognised, but technological challenges stymied their application. ‘At the biological level, there were three major challenges with mRNA technology: its reactivity, stability and the delivery method into cells,’ explains Aneesh Thakur, who is developing mRNA vaccines at the University of Copenhagen. ‘Now that we have addressed those three biggest issues, it’s definitely game-changing.’

BioNTech and Moderna had already perfected their mRNA-based technology before the pandemic arrived. It was this that enabled the rapid development of the new vaccines. It took just two days after the SARS-CoV-2 genome was sequenced by Chinese scientists for Moderna to select the appropriate sequence of the virus’s DNA to target with a vaccine.

The events of 2020 are now seen as an endorsement for this technology, which could be leveraged to treat a wide range of diseases and disorders. According to Özlem Türeci and Uğur Şahin, the co-founders of Germany’s BioNTech, the successful development of mRNA vaccines for Covid-19 opens up the possibility of developing similar vaccines for other infectious diseases, including tuberculosis and malaria, and for any pandemic-causing viruses that emerge in the future.

HIV is one example. Scientists have thus far failed to produce a vaccine against HIV because of its ability to rapidly mutate and evade the immune system. But some biotech firms are banking on mRNA-based vaccines to change that. IAVI recently revealed that its mRNA-based HIV vaccine was able to induce the correct immune response in 97 per cent of participants in early clinical trials. The same approach could be used to build vaccines against other difficult-to-treat viruses, including dengue, Zika and hepatitis C, and malaria. Other companies have joined the effort: ConserV Bioscience and eTheRNA announced a collaboration on 8 March, which aims to deliver an mRNA-based HIV vaccine. 

The technology could also improve the vaccines that we already have. Infectious diseases often outpace conventional vaccines by evolving new mutations. Influenza is one example: manufacturers must decide which strains to target months before the annual season, limiting vaccine efficacy to around 50–70 per cent. But mRNA-based vaccines can be very quickly manufactured to target a range of viral subtypes. Since 2018, BioNTech and Pfizer have separately been working on a ‘universal’ mRNA-based flu vaccine that they hope will soon circumvent the need for seasonal influenza jabs. 

The very nature of an mRNA-based approach to medicine also has applications for other, non-infectious diseases. Mainstream drug development has focused on building small molecules to manipulate the behaviour of proteins (which form the major building blocks, cellular architecture and molecular machinery of the body). However, geneticists estimate that only 10–14 per cent of proteins are ‘druggable’. Targeting mRNA instead means influencing which proteins get made in the first place, before they have a chance to lead to disease or cause a condition to progress.

This approach has significant potential in cancer treatment. Cancer cells have constellations of unique proteins on their surface. By packaging the instructions for such proteins into mRNA-based vaccines, doctors hope to be able to prime the patient’s immune system to recognise and fight cancer. BioNTech already has an RNA-based therapy for skin cancer in clinical trials that tailors a unique mRNA vaccine to each patient; Moderna is building mRNA therapies that train the immune system to recognise cancerous proteins created by mutations in a gene called KRAS, which is involved in around 20 per cent of cancers; and CureVac is conducting trials of a similar mRNA-based vaccine for treating lung cancer.

With RNA, there is also the possibility of triggering the body to produce proteins that help fight disease. Moderna and AstraZeneca are jointly developing an mRNA-based medicine that stimulates the body to produce a protein which encourages the regrowth of blood vessels – a treatment that could be used to help rejuvenate cardiac blood vessels after heart attacks.

Other biotech firms are using the technology to improve treatments for diseases where patients fail to produce a necessary protein because they lack the corresponding gene, such as phenylketonuria and glycogen-storage disorders, for example, which cause the liver and kidneys to enlarge.

Expectations are high but there’s still a long way to go. ‘It’s not the end here – it’s almost like a first-generation iPhone. The technology will be continually improved upon and refined,’ says Thakur. ‘The next generation of mRNAbased vaccines and therapies will be far safer and more effective, even than what we’ve already seen with Covid-19.’