Vaccines to prevent SARS-CoV-2 infection were not the first attempt at utilizing the promise of mRNA in a therapeutic setting. From the discovery of mRNA in the 1960s, many scientists, clinicians, and patients have contributed findings and advancements that provided the knowledge and experience necessary to rapidly progress from sequencing of SARS-CoV-2 to emergency use authorizations for mRNA-based COVID-19 vaccines. For example, mRNA is rapidly degraded once produced inside the cell to provide protection against detrimental protein build up and only provide protein during a relatively short timeframe. This presents a problem when limitations in protein production hinder the proper immune response to vaccine treatment. However, scientists have not only figured out ways to deliver exogenous mRNA inside a cell, but they have also added features to increase longevity of mRNA translation to allow enough protein to be produced for a therapeutic effect.
Viral mRNA vaccines present a relatively simple therapeutic use case. A viral protein is sequenced and used to create an mRNA molecule that once injected is used by the patient’s cells to create a protein that activates the adaptive immune response and arms it to fight off future infections. Similarly, tumor proteins can be sequenced, and a similar strategy taken, but instead of fighting off future infections, the immune system can be triggered to kill existing cancer cells. With localized infections or disease, challenges can arise with honing the mRNA/proteins to the area of concern. Thus, like advancements made in delivery and longevity, efforts are also focused on how to effectively deliver mRNA to specific tissue types, cell types, and organs.
Despite additional breakthroughs needed in specific use cases, mRNA therapeutics have provided a platform for rapid and robust vaccine development and the opportunity to change the course of human health. Given the unprecedented timelines achieved with mRNA vaccines during the pandemic, one can envision the days of decades spent on vaccine development as being merely a thing of the past. The basics of mRNA, the key instructions for a cell to make a protein, make it a useful therapeutic strategy for producing proteins in vivo to fight off future infections or existing disease. This provides many advantages such as reduced complexity and cost in manufacturing and the ability to leverage the human body for necessary post-translational modifications, both of which can present challenges in historical therapeutic protein expression systems.
mRNA manufacturing workflow
Manufacturing advantages aside, like many other therapeutic manufacturing workflows, every step in the mRNA process builds upon the prior step. Plasmids are critical starting materials used for mRNA synthesis, after which the resulting purified mRNA is encapsulated for more efficient stability and delivery. The encapsulated final drug product must then be sterile-filled, packaged, labeled, and shipped to its final clinical destination. Additionally, in-process and final release testing are critical to ensure robust Chemistry, Manufacturing, and Controls (CMC). As the manufacturing process progresses, every step adds complexity and cost, so it’s important to ensure steps are compatible and integrated into each other.
Given the recent success of mRNA therapeutics, the industry has experienced some constraints in development and manufacturing capacity. The expectations around pace have also increased and thus it’s a race to fill gaps as quickly and efficiently as possible to enable rapid progression toward each upcoming milestone. That’s why companies such as Thermo Fisher Scientific have ramped up service offerings and are taking a flexible approach to filling gaps and providing integrated service offerings that can get mRNA products to clinic and market faster. This infographic explores each intertwined step in the mRNA manufacturing process and outlines how Thermo Fisher Scientific’s flexible approach can get your mRNA product to clinic and market faster.
View the full mRNA workflow infographic here.
- The tangled history of mRNA vaccines, https://www.nature.com/articles/d41586-021-02483-w