Researchers have been working on mRNA-based drugs for decades—primarily in therapeutic areas such as cancer. COVID-19 provided the first large-scale opportunity for the platform to reach the market.  

mRNA indications and the surrounding research are extremely complicated. The research, development, and manufacturing of mRNA continue to develop into more advanced vaccines and a variety of therapeutic modalities. Underlying science, such as the mode of action for example, will become even more specialized. This added complexity can pose communication challenges and may influence how new technologies are understood. This can contribute to hesitancy, even as mRNA as the platform matures, and its use cases expand. 

How does analytical science ensure the purity and safety of modern vaccines at scale? 

Analytical science is foundational to ensuring that (modern) vaccines are safe and effective and meet defined quality standards, like purity and consistency. mRNA vaccines are defined and controlled through a set of product quality attributes (PQAs) and critical quality attributes (CQAs). One example of a CQA is the integrity of mRNA, which is a requirement to produce the target protein in a patient’s body after administration, and therefore critical for the effectiveness of a vaccine. Assays for mRNA integrity determine the intactness of mRNA.  

Another example, purity, can be divided into multiple different CQAs: mRNA purity, 5’capping efficiency, 3’ poly(A) tail length, and whether the full-length mRNA remains intact or if it has fragmented, to name a few. Techniques such as capillary gel electrophoresis (CGE) are used to quantify intact mRNA to determine purity versus degraded fragments, and can determine 3’ poly(A) tail length and distribution¹, providing a clearer picture of product quality.  

Multiple analytical approaches are used to assess the long list of attributes, and the approach continues to evolve alongside the platform. This rigorous analytical framework ensures that every dose meets defined safety and performance criteria. 

Analytical science is also used during process development to understand the best conditions for manufacturing and purification, as well as storage, and formulation. 

 Why is greater transparency in vaccine testing critical for maintaining public trust? 

As mentioned previously, the complexity of the research can pose communication challenges and may influence how new technologies are understood. Maintaining trust requires clear communication. Translating complex scientific data into accessible explanations, ensuring credible experts engage in discussions, and highlighting real-world outcomes can all help support informed understanding. 

This understanding will prove important for mRNA technologies in the future. mRNA-based drugs show tremendous potential in cancer treatments, rare disease therapies, and other personalized and individualized applications.  

1 Di Grandi D, Dayeh DM, Kaur K, Chen Y, Henderson S, Moon Y, Bhowmick A, Ihnat PM, Fu Y, Muthusamy K, Palackal N, Pyles EA. A single-nucleotide resolution capillary gel electrophoresis workflow for poly(A) tail characterization in the development of mRNA therapeutics and vaccines. J Pharm Biomed Anal. 2023 Nov 30;236:115692. doi: 10.1016/j.jpba.2023.115692. Epub 2023 Sep 2. PMID: 37696189. 

https://pubmed.ncbi.nlm.nih.gov/37696189/