Rational design of stationary phase carriers for oligonucleotide separations using liquid chromatography (OLIGOCHROM)

Oligonucleotides (ONs) are synthetic polymers of nucleic acids that are currently revolutionising disease treatment. This is because ONs can directly influence protein expression by binding to DNA or RNA. A growing number of ONs are currently being developed for the treatment of various diseases that were previously difficult or even impossible to cure with traditional small-molecule drugs. During ON production, many closely related impurities are formed that must be carefully monitored and controlled. High-performance liquid chromatography (HPLC) is used as the preferred analytical technique for this purpose. However, due to the high complexity of ON samples, their analysis via HPLC is currently very challenging. This is mainly because the effect of specific column parameters on ON separation is poorly understood. This forms a real bottleneck in the pharmaceutical development of ONs, especially since the number of therapeutic ONs in development is rapidly increasing. This project will therefore conduct detailed research into the key column parameters for efficient ON analyses. The ultimate goal is to gain insight into how to design the ideal column for optimal ON separations, to accelerate both ON analysis and the development of therapeutic ONs in the future.