Emma Harry, a European Applications Lab Manager at Waters, outlined some of the services that Waters offers for oligonucleotide mapping. The oligonucleotide market is growing rapidly, with its value expected to double by 2027. In 2023, approximately 11 FDA-approved oligonucleotide therapeutics were on the market. However, strict manufacturing standards and the complexity of these therapeutics present limitations.
Waters aims to assist the biopharma industry with these challenges. Harry specifically highlighted the technologies available at Waters for oligonucleotide mapping. The XEVO G3 QToF calibrates mass spectrometry and offers higher-resolution and user-friendly functionalities. The BioAccord System is a user-friendly QC monitoring system. The CONFIRM Sequence is a new software specifically designed to sequence oligonucleotides. Using the libraries, a user can customise their oligonucleotide and once the oligonucleotide information is added to the system it creates a dot map for the oligonucleotide sequence.
Harry discussed three samples: Gem 91, a 40MER, and several isomers. The XEVO G3 generated Gem 91 data. Gem 91 is a 25-mer phosphonothioate oligonucleotide and the software took very little time (6 minutes) to generate the sequence and predicted 100% coverage. Harry added that scientists can also observe fragmentation. However, for larger oligonucleotides, the software sometimes struggles to sequence the middle section, so the team is working on running an hVIP, to tackle this. Harry mentioned that low-level impurities are detected down to 0.08%, showing the system's sensitivity, making it suitable for QC and regulatory compliance.
Furthermore, the potential of Ion Mobility Spectrometry (IMS) was explored. By providing an orthogonal separation based on size and shape, IMS significantly enhances resolution. The Cyclic
IMS system, which allows multiple passes of ions, was able to effectively distinguish isomers, that would otherwise appear as a single peak in traditional mass spectrometry. This capability is highly valuable for those seeking higher-resolution separations.
In conclusion, Waters' analytical XEVO G3 QTOF system and CONFIRM Sequence software, offer a powerful and efficient approach to oligonucleotide mapping. The application of ion mobility technology further enhances analytical capabilities, particularly for distinguishing structural variants.
