Automated workflows for RNA and oligonucleotides

Nucleic acids form the active pharmaceutical ingredient (API) and often incorporate modified nucleotides to improve stability or lower immunogenicity, making them critical to drug efficacy. 

Separation from synthesis-related impurities is important for characterization and CMC testing. For mRNA, understanding 5’ capping efficiency and 3’ poly(A) tail heterogeneity is a key regulatory requirement. 

Sequence mapping by mass spectrometry enables you to confirm the identity of these molecules and to identify and localize modifications within the sequence. 

Waters offers high-performance column chemistries and fit-for-purpose compliance-ready LC-MS workflows ideal for identifying and locating sequence modifications. Waters solutions combine unparalleled separations performance with robust and accurate mass analysis to support characterization, monitoring, and quality control (QC) requirements. 

Viral vector characterization and monitoring

Nucleic acid sequences may be “encapsidated” in viral vectors, designed by nature to enter cells and release their genetic payload. The capsid of these viral vectors varies to provide for targeted delivery. The native genetic material is replaced with a transgene sequence that gets transcribed and translated into a functional protein. Viral vectors are being developed for both ex-vivo gene-modified cell therapies (e.g., Car-T) and in-vivo gene therapies. 

The development and characterization of different serotypes and the monitoring of critical quality attributes across development, manufacturing, and QC is important to ensuring safety and efficacy. Waters offers key analytical methods, including empty/full analysis using anion exchange (AEX) chromatography, post-translational modification (PTM) analyses, confirming viral protein ratios using reversed-phase (RP) chromatography, and aggregation and titer analyses using size-exclusion chromatography (SEC).