The pharmaceutical industry’s success in the race against the clock to develop a vaccine against COVID-19 has popularised and socialised the term “mRNA vaccine” beyond the biomedical research sector. Although it may seem that this therapeutic technology originated during the fight against the COVID-19 virus, the reality is that it has been in development for 30 years . What the pandemic did was to increase resources in this field of research, accelerating development times and, subsequently, putting the focus on other applications of this technology as well.
What mRNA therapy is and how it works
All living things – from humans to bacteria – require the constant generation of proteins to survive. The mechanism of protein generation is initiated by copying fragments of DNA – a process known as transcription; these copies are messenger RNA, a macromolecule containing genetic information from DNA called mRNA. Cells use the information in the mRNA to make proteins, and then the mRNA is broken down. This process is constantly repeated inside cells. A dysfunction in this process can lead to metabolic impairment, serious illness and/or even life-threatening conditions.
The technology of mRNA therapy uses this cellular mechanism: introducing synthetic mRNA into cells, forcing them to use it as if it were their own, producing proteins. It is worth mentioning that mRNA presents no risk of genomic integration, unlike other DNA-based vaccines.
Fields of application
The principle of mRNA therapy is to deliver the mRNA molecule to cells which, using their internal mechanism, convert the mRNA into functional proteins. In this way, its use can be broad: from vaccines, to protein replacement therapies, or treating genetic dysfunctions. Some of these applications were already being investigated before the COVID-19 pandemic.
Vaccines for infectious diseases
This involves making the body generate a specific protein from the surface of a virus (commonly known as spike proteins); this protein is harmless to the human body, although the immune system does detect it as foreign and produces specific antibodies against it. In the case of infection, the antibodies already created act against the infectious agent, preventing it or minimising its consequences.
This is the strategy that has been followed to generate the COVID-19 vaccine and is now being investigated for use in other infections. This is the case for the AIDS virus, for which Moderna announced last August 2021 the start of phase 1 studies of two vaccines .
Another important application is the influenza vaccine, where Pfizer, Moderna and Sanofi, among others, are investigating its use. The mRNA technology is faster to adopt and more flexible than other vaccine technologies, so it can be more easily adapted to the influenza virus, which seasonally undergoes genetic changes – i.e. new strains.
Rabies virus is another field of research for the application of an mRNA vaccine. In 2020, CureVac announced positive results from phase 1 clinical trials.
There has been some interesting research in this field, even before the COVID-19 pandemic. In 2013, Nature Biotechnology published a study showing that intramyocardial injection of endothelial growth factor-encoding mRNA induced vascular regeneration in myocardial infarction in a mouse model . Moderna currently has an mRNA-based therapy for this growth factor in a phase 2 clinical trial.
Cancer immunotherapy is, after the COVID-19 vaccine, where mRNA technology is being used the most, with published studies and several ongoing trials. Research in this field has existed for more than a decade. It is based on introducing mRNA to express tumour antigens to stimulate the immune system against cancer cells. This technology also allows personalised therapies that identify particular mutations specific to each patient.
Several pharmaceutical companies are researching and developing mRNA therapies for cancer immunotherapy. For example, Moderna has several clinical phase 1 and 2 treatment trials. BioNTech is developing clinical phase treatments for melanoma, prostate and ovarian cancer, among others(5).
Treatments for rare diseases
mRNA technology also has potential for the treatment of rare genetic diseases associated with dysfunctions due to protein deficiency or misexpression. This is the example of ornithine transcarbamylase enzyme deficiency, a genetic disorder that renders this enzyme ineffective . This enzyme is necessary for urea metabolism and its deficiency or ineffectiveness affects the ability to eliminate ammonia from the body. Arcturus Therapeutics is developing an mRNA treatment for this disease.
Challenges of mRNA therapies
mRNA therapies still have a number of potential challenges to overcome. Stability of the mRNA is a key issue: it is an unstable molecule, so the method and/or vehicle of transmission is essential, and related to this is the need to develop transfer methods that are selective to the specific cells into which the mRNA is introduced. Another important aspect is that some of these therapies will require chronic dosing of mRNA, so the immune system may react, reducing the effectiveness of the treatment.
Market outlook and growth
The mRNA technology has been around since before the pandemic, and several companies have clinical trials underway. However, there are few market studies of mRNA-based therapies and their conclusions differ, although most agree that there is overall growth. For example, BCC Research estimated in 2021 that the mRNA therapeutics market would grow from $46.7 billion in 2021 to $101.3 billion in 2026. Verified Marked Research estimates that the market will reach $115.11 billion by 2030.
The success of the COVID-19 mRNA vaccine has pushed the research of this technology into several pharmaceutical fields. Clinical trials by several companies and ongoing research will determine the potential of this technology in the coming years.
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- mRNA-based therapeutics: powerful and versatile tools to combat diseases, Shugang Qin et al., Springer Nature, 2022
- mRNA therapeutics: beyond vaccine applications, Balkrishen Bhat et , Trends in Molecular Medicine, 2021
- mRNA Technologies: A Primer, Congressional Research Service, 2022
- Modified mRNA directs the fate of heart progenitor cells and induces vascular regeneration after myocardial infarction, Lior Zangi et al., Nature Biotechnology, 2013
- 7 potential applications of mRNA-based therapies, Brian Buntz, Drug Discovery & Development, 2022