Characterization of Apolipoprotein C3 LNA/DNA Impurities and Degradation Products by LC/MS/MS

摘要

Antisense oligonucleotides and small interfering RNA are promising therapeutic interventions for silencing molecular targets that otherwise are not drugable. Their therapeutic implementation is hindered by poor bioavailability and in vivo stability. Incorporation of locked nucleic acids (LNA) into RNA and DNA sequences increases their specificity, sensitivity, and stability, thus enabling their use as biotherapeutics. A specific LNA/DNA construct was developed to silence the Apo C3 gene, which is essential to the assembly and secretion of very low density lipoprotein (VLDL), a precursor to LDL. LDL is involved in cholesterol transport and cardiovascular disease. The Apo C3 LNA/DNA gapmer comprises 14 residues with the following sequence: βZ*βZ*βA*dG*dT*dA*dG*dT*dC*dT*dT*βT*βZ*βA, where　β　Z, and * correspond to LNA, 5-methyl cytosine, and phosphorothioate, respectively.