Downstream processing of oligonucleotides: meeting regulatory and commercial demands

“Each conjugation strategy brings its own set of purification challenges, and these must be worked through systematically before scale‑up.” As the pipeline of oligonucleotide therapeutics continues to expand, and as approved compounds begin to address broader patient populations, the demands placed on downstream processing are intensifying. Purification, finishing, and impurity control must now operate at greater scale, with higher complexity molecules, and under increasingly scrutinized regulatory frameworks. Nucleic Acid Insights brought together a panel of experts to discuss the key challenges and emerging solutions in this space: Piotr Putaj (Director of Oligonucleotide Chemistry, VICO Therapeutics), Jared Jackson (Oligonucleotide Scientist), and Maria del Carme Pons Royo (Postdoctoral Researcher, MIT). The discussion covers purification strategies, impurity management, conjugation complexity, the role of analytics, and the future of the field, alongside the distinct downstream challenges presented by mRNA therapeutics.