LC-HRMS analysis of the antisense oligonucleotide Mipomersen (Kynamro®)

Antisense oligonucleotides (ASOs) have an outstanding therapeutic potential, since they are used for the therapy of genetic diseases. Due to the specific binding of an ASO to the complementary sequence of the RNA of a target protein its formation is suppressed. The ASO Mipomersen (commercially available as Kynamro^®) was developed to treat homozygous familial hypercholesterolemia by inhibiting the production of the low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) and therefore by reducing their concentration in blood. In this application note, Mipomersen is used as a model for the analysis of ASOs using LC-HRMS according to Y. Sun et al. [1]. They worked with an YMC-Triart C8 metal-free column which is an excellent choice for oligonucleotide analysis.