Therapeutic oligonucleotides: the state-of-the-art in purification technologies

Currently, there are over 40 oligonucleotide-based pharmaceutical products in various stages of clinical development for the treatment of an assortment of life-threatening diseases. As a result, the production of synthetic oligonucleotides has become increasingly important, with applications in antisense-, aptamer-, ribozyme-, immunostimulatory CpG molecule- and RNAi-related therapeutics. Due to the enormous commercial interest in these technologies, the manufacturing and purification processes for oligonucleotide production have been furtive and practiced in a confidential environment. As a result, limited information on large-scale processing is available in the scientific literature. The purpose of this article is to review the current state-of-the-art in oligonucleotide purification technologies, which have resulted in drug products meeting stringent therapeutic specifications. An indication of new and emerging purification technologies, including simulated moving bed- and membrane-based separation, is given.