text: Yamamoto et al. in 2012 demonstrated that BNA-based antisense therapeutics inhibited hepatic PCSK9 expression, resulting in a strong reduction of the serum LDL-C levels of mice. The findings supported the hypothesis that PCSK9 is a potential therapeutic target for hypercholesterolemia and the researchers were able to show that BNA-based antisense oligonucleotides (AONs) induced cholesterol-lowering action in hypercholesterolemic mice.  A moderate increase of aspartate aminotransferase, ALT, and blood urea nitrogen levels was observed whereas the histopathological analysis revealed no severe hepatic toxicities. The same group, also in 2012, reported that the 2,4-BNA[NMe] analog when used in antisense oligonucleotides showed significantly stronger inhibitory activities which is more pronounced in shorter (13- to 16mer) oligonucleotides. Their data led the researchers to conclude that the 2,4-BNA[NMe] analog may be a better alternative to conventional LNAs.