Messenger RNA: the technology of the future?

According to experts, messenger RNA technology has many potential applications against several diseases, including cancers. A new generation of vaccines is about to emerge beyond the scope of Covid-19.

Will the current health crisis serve to reveal a new phenomenon? Sixty years after the discovery of the concept, messenger RNA technology may soon rewrite the rules of modern medicine. This unprecedented vaccination technique is not based on inoculation with a deactivated or mitigated virus. It is not based on creating a protein or an antigen either. The technology simply transports genetic information which encodes a specific antigen. Once injected, the "messenger" enables cells to manufacture a specific protein, i.e. the antigen. When the immune system comes into contact with this antigen, it automatically produces the corresponding antibodies. In short, mRNA puts the organism to work by showing it how to defend itself against a virus.

Faster, simpler and cheaper

This technology has several significant advantages, notably in terms of timing. Unlike traditional methods, it does not require laboratory culture involving cells and chicken eggs, etc. It took fewer than 60 days between sequencing the full genome of the new coronavirus and initial testing on humans. A year after the first cases appeared in China, two vaccines of this type are currently in widespread use. This is an absolute record in terms of rollout speed. On a comparable basis, the Ebola vaccine required 5 years of work before it was available. Over the past decade, the average estimated development period for the 21 vaccines approved by the FDA was 8 years, according to the JAMA medical review.

Another notable advantage is that RNA-based vaccines can be produced very quickly in large quantities and for a low cost. As they are easier to manufacture, they can also be transformed more easily. This technology can also take genetic mutations into account in a very short space of time, without any major impact on the manufacturing procedures and without jeopardising production lines. This flexibility and reactivity are indispensable factors for an unknown disease like Covid-19. It provides a major advantage for treating unstable emerging pathologies. These advantages must be put into perspective however.

A technology which still needs to prove its worth over time

Although it appears highly promising and advantageous, this methodology is only just at its beginnings. No other mRNA vaccines had been authorised for human use before last autumn. Despite the results of initial clinical and pharmaco-epidemiological trials, its real world efficacity remains to be proven. The degree and duration of immunity will be decisive parameters, particularly among high-risk populations. Under the current understanding, the safety of vaccines must also be analysed. Without sufficient scientific back-testing, long term surveillance of undesirable side effects will be indispensable. As a first encouraging sign, no serious side effects have been observed during the testing phases, or in the field. In the UK, a simple warning has been ascribed to the product currently in use for individuals with a history of extreme allergic reactions to vaccines, drugs or foods. The fragile nature of mRNA vaccines is a further hindrance to their rollout. They require sophisticated logistics to ensure their preservation. Given their instability at room temperature, some of these vaccines need to be stored at very low temperatures. Distribution could therefore prove problematic, given the stringent preservation conditions and the associated costs. Temperature conditions must be fully respected to avoid deterioration.

Combating infectious diseases…

Despite the current uncertainties, messenger RNA technology heralds the development of a new generation of vaccines, capable of covering a wide range of hitherto unsatisfied medical needs. According to experts, this technology could facilitate the implementation of new mechanisms and novel administration methods. Potential applications among infectious diseases, including hepatitis, cardiovascular, genetic and respiratory illnesses, appear to be almost infinite. Several studies are underway to improve the treatment of heart failure, cystic fibrosis, bronchiolitis, mononucleosis and HIV. The most advanced projects include a vaccine against cytomegalovirus, which could enter its final development phase as early as next year. In the medium term, the development of a more complete vaccine against seasonal influenza could also become a reality. Combining this vaccine with regular Covid-19 booster jabs is even being considered. One thing is certain however: science is making progress in great strides, as reflected in several cases. For example, a research team at Pennsylvania University has developed an efficient messenger RNA against a particular strain of the Zika virus*. A very low intradermic dose could trigger a powerful lasting immune response. Initially trialled on rhesus monkeys, a prototype is currently being tested on humans.

… and cancers!

Beyond the scope of infectious diseases, mRNA also has promising outlook in the field of oncology. This technology could enable the immune system to target and destroy cancerous cells, without weakening the organism. As an encouraging signal, most research programmes currently underway are targeting curative uses. Some initial results have been extremely promising. Among head and neck cancers, the combination of medical immunotherapy and a new generation vaccine appear to have reduced tumours in 5 out of 10 participants in a phase I clinical trial, shown in intermediary data presented at the latest Society for Immunotherapy of Cancer annual congress**. Tumours in two of the patients had completely disappeared. Although this is undoubtedly good news, there was no response for 17 patients with colorectal cancer however. At least, this new class of vaccines harbours the promise of more specifically targeted, personalised and more readily accessible medicine. If the efficacity and innocuity of these products were to be demonstrated on a large scale, the last curbs on the widespread use of messenger RNA vaccines would be definitively removed. The use of this method would then be able to be intensified, reaping significant medical and economic benefits. With a strong focus on healthcare innovation, Candriam is attentively monitoring the numerous developments underway in this fast-changing sector. Thanks to its committee of experts, Candriam will identify and support the most pertinent technologies, players and projects.