mRNA Purification: Can a New Method Remove RNA

Why do mRNA medicines need unwanted RNA removed?

IndexBox projects growing demand for nucleic acid raw materials through 2035, supported by applications including mRNA vaccines and gene therapies. That commercial outlook provides context for a practical pharmaceutical challenge: producing useful RNA also requires identifying and controlling unwanted material. The forecast itself does not establish that any experimental medicine works or will receive approval. [IndexBox market outlook](https://www.indexbox.io/blog/nucleic-acid-raw-materials-market-forecast-to-2035-growth-accelerates-on-mrna-vaccine-and-gene-therapy-demand/)

Manufacturers produce mRNA through a process called in vitro transcription, which copies a DNA template into RNA. Depending on the process, this can also generate double-stranded RNA, or dsRNA. Cells can recognize these byproducts through innate immune sensors. WHO's regulatory considerations identify dsRNA as an impurity that should be removed or measured and controlled when the manufacturing process produces it. This is distinct from the intended immune response to a vaccine's target protein. [WHO mRNA vaccine guidance](https://www.who.int/publications/m/item/annex-3-mRNA-vaccines-trs-no-1039)

What did the new mRNA purification study demonstrate?

Kyle Tynan and colleagues at the National Institute of Standards and Technology and the Institute for Bioscience and Biotechnology Research reported a size-exclusion chromatography method in Biomedical Chromatography. Their laboratory system separated the unwanted dsRNA from the target mRNA with a resolution factor of 1.6, a measure of how distinctly the components emerged during chromatography. The researchers described this as baseline separation. [Published study](https://pubmed.ncbi.nlm.nih.gov/42306876/)

The reported 81.8% recovery measures how much target mRNA was retained through the purification procedure. It is not a percentage improvement in vaccine protection, a measure of final product purity, or a reduction in side effects. The study establishes a laboratory separation result; it does not demonstrate improved treatment outcomes or establish commercial manufacturing performance. [NIST research summary](https://www.nist.gov/publications/purification-double-stranded-rna-impurities-vitro-transcribed-mrna-using-size-exclusion)

Could better RNA purification improve future treatments?

Earlier research provides biological support for removing dsRNA. In a 2019 study in Molecular Therapy–Nucleic Acids, Markus Baiersdörfer and colleagues developed a cellulose-based purification method. One experiment found approximately 90% less dsRNA in the recovered mRNA fraction than in the starting material. The researchers also reported improved protein production from purified mRNA in animal experiments. These findings concern a different purification method and cannot be used as a direct performance comparison with the newer chromatography study. [Cellulose purification study](https://pmc.ncbi.nlm.nih.gov/articles/PMC6444222/)

The same research illustrates why purification alone cannot determine a medicine's biological effects. In mice, the inflammatory response also depended on whether the RNA contained modified nucleosides, showing that RNA chemistry and impurity removal interact. WHO consequently treats purity as one part of a broader evaluation that includes product characterization, biological activity, and clinical safety and efficacy. The practical implication is that improved separation methods may support drug development, while claims of safer or more effective treatment must be established for each product. [Experimental findings](https://pmc.ncbi.nlm.nih.gov/articles/PMC6444222/), [WHO regulatory considerations](https://www.who.int/publications/m/item/annex-3-mRNA-vaccines-trs-no-1039)