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

Oligonucleotides (ONs) are synthetic nucleic acid polymers that are revolutionizing the treatment of
diseases as they can directly influence the expression of a protein by binding to its DNA or RNA. An
increasing number of ONs is nowadays under development to treat a variety of diseases that were
previously hard or even impossible to cure with traditional medicines based on small molecules.
During the production process of ONs, a large number of closely related impurities is typically formed
that need to be carefully monitored and controlled. For this purpose, High-Performance Liquid
Chromatography (HPLC) is used as the analytical technique of choice. Due to the high complexity of
ON samples, their analysis via HPLC is, however, very challenging at present. This is because the
influence of specific column parameters on the resulting separation of ONs is currently poorly
understood. This represents a true bottleneck in their pharmaceutical development, as the number of
therapeutic ONs under investigation is rapidly growing. Therefore, this project aims to perform a
detailed investigation of the most important column parameters for efficient ON analysis. The
ultimate goal is to obtain insight into how the ideal column for optimal ON separations should be
designed, to speed up the analysis and pharmaceutical development of therapeutic ONs in the future