Episode 6: Analysis of the complex component parts of Mergo™: an oligonucleotide-based drug delivery system for the treatment of immune and genetic diseases

As interest in oligonucleotide therapeutics increases, there is an ever-growing need for analytical techniques that can properly analyse and quantitate these complex biomolecules. Mass spectrometry (MS) is required to analyse impurities, degradants, and other biological/chemical modifications and is the method of choice for the analysis of synthetic oligonucleotides. Sixfold Bioscience, in collaboration with the National Measurement Laboratory (NML) have been using the Agilent AdvancedBio 6545XT LC/Q-TOF to develop a method to analyse complex oligonucleotides of various lengths with volatile ion pair reagents. This method is used for quality control of oligonucleotides that are subsequently assembled into Mergos™ for use in in vivo applications. In addition to the analytical capabilities currently being utilised by Sixfold, the Agilent 1290 Infinity II Preparative system is also being used for oligonucleotide purification. Both reverse-phase (C18) and anion-exchange (IEX) chromatography is regularly carried out to assist in Sixfold's purification workflow. As a result of this work, and as an extension to the work currently being carried out by the Tate group at Imperial College, a Metabolomics group is in the process of being formed at the Molecular Sciences Research Hub. This group will aim to solve challenges related to the analysis of biomolecules and will take advantage of the combined know-how and expertise of scientists at Imperial College, Sixfold Bioscience and Agilent. Dr James Rushworth, Research Associate at Sixfold Bioscience. For Research Use Only. Not for use in diagnostic procedures. DE44320.2788078704