Antisense apolipoprotein B-100 as novel treatment for hypercholesterolemia: focus on ISIS 301012

Antisense oligonucleotides (ASOs) are single-stranded DNA-like molecules, which can effectively limit the availability of specific mRNA, resulting in less translation of the encoded protein. Since these antisense drugs largely distribute to hepatic cells, liver targets are preferred candidates for antisense strategies. ISIS 301012 is an ASO that inhibits the production of apolipoprotein (Apo)B-100, the major Apo of atherogenic lipids that is produced predominantly in the liver. Since adequate lowering of atherogenic lipoproteins cannot be achieved in all patients at increased cardiovascular risk, the use of ApoB antisense has emerged as a promising, novel modality to reduce hepatic ApoB secretion.