Researchers worldwide are rapidly developing novel, ground-breaking applications for mRNA technology in the diagnosis and treatment of diseases, owing to their rapid development and production times without the need for a massive manufacturing facility. Besides, mRNA vaccines are produced via biochemical rather than biological processes, in contrast to traditional vaccine technologies that rely on cell culture or other means (for example, chicken eggs). This simplifies the manufacturing process, making it more reliable and portable than previous vaccine producers. The time it takes to make the active pharmaceutical ingredient for an mRNA vaccine is also drastically reduced due to its ease of production, taking only three to seven days compared with one month for a non-replicating viral vector and a DNA-based vaccine. In fact, according to the World Health Organization, due to the unique properties of mRNA technology and the absence of cell-based biological components, mRNA vaccines may be manufactured in large quantities by already operating pharmaceutical manufacturers, even if these firms have no prior expertise with vaccines.
Billions of dollars have been invested in mRNA therapy, and a growing number of biotechnology companies, including Moderna, CureVac, BioNTech, Argos Therapeutics, Translate Bio, Ethris and Arcturus have emerged with applications in oncology, and genetic, cardiovascular or infectious diseases (Table 1). In fact, according to ClinicalTrials.gov, there are more than 200 mRNA-based vaccine clinical trials for other diseases than COVID-19 (almost 100 just for cancer) that have either been completed or are actively recruiting participants. Based on the results of these studies, we know that a vaccine’s risk–benefit profile must strike the right balance between immunological and inflammatory activation. In addition, early cancer clinical trial findings with mRNA vaccines as monotherapy and in combination with checkpoint inhibitors have shown positive results. This indicates that these vaccines exhibit promising benefits even for complex diseases such as cancer or HIV.
In fact, from a clinical perspective, mRNA vaccines have the potential to provide broad-spectrum immunity, along with the implementation of quick-response manufacturing. Since mRNA vaccines are constrained only by the efficacy of the recipient’s immune system against the disease, locating the corresponding mRNA is a straightforward task if a promising protein candidate is discovered. With a speedy manufacturing pipeline in place, these novel vaccine technologies might enable production and distribution within 1–3 months of the emergence of a new variant.
In the future, the next generation of lipid nanoparticles will face new challenges, such as improved stability and multifunctionality, which should be considered in their design to increase tolerance and safety18. Forthcoming developments also include single-dose second-generation vaccines and ‘multi-variant’ vaccines that might offer defence against newly developing viruses. The development of mRNA vaccines, which can prevent a variety of diseases with a single injection, has the potential to drastically streamline the current immunization schedules. In the search for a ‘multi-variant’ vaccine, researchers at the National Institutes of Health have identified a new target — the N (nucleocapsid) protein — which rarely mutates and targets multiple chemokines, weakening the body’s immune response. Personalized vaccines are another future application of mRNA vaccines, which are manufactured using a generic approach that may be used to produce mRNA vaccinations targeting patient-specific antigens quickly. In addition to directly immunizing patients, mRNAs can be used in cellular therapies to transfect patient-derived cells ex vivo to change cell phenotype or function. These cells are then expanded and delivered into the patient.
Moreover, artificial intelligence and machine learning will certainly be useful to design highly structured ‘superfolder’ mRNA strands21 and make mRNA vaccines safer and more durable (with fewer refrigeration requirements). A multi-pronged approach to reducing the world’s substantial disease burden by making mRNA vaccines more widely available, affordable, efficient and safe is of utmost importance. Another potential development would be self-boosting vaccines protected and delivered by stable nanoparticles or local scaffold patches (for example, microneedles) that can be administered in a single injection and do not require the patient to return for boosters. These self-boosting platforms can be loaded with multiple doses into a single shot, which is especially relevant for populations that don’t have easy access to medical services.
This is where genetics meets nanomedicine. This discussion demonstrates how genetics has evolved in the past 20 years since the Human Genome Project, allowing hundreds of millions of people to be vaccinated with mRNA vaccines and hindering the pandemic. The ability of mRNA therapeutics to better link the biology of human physiological systems with new mRNA payloads and in vivo nanodelivery systems, by providing options for continuous dosage with acceptable safety profiles and greater precision, length and duration, may be critical to their success. It is a new age for the technology and manufacture of mRNA vaccines, which stands as a monument to the advances that science has made over decades of research at the intersection of genetics and nanomedicine. This intersection will go down in history as one of science and medical research’s greatest achievements.