P901SL

P901SL is a 2′,4′-bridged nucleic acid (BNA)-modified antisense oligonucleotide (AON) designed to target the messenger RNA (mRNA) of proprotein convertase subtilisin/kexin type 9 (PCSK9). Developed by researchers at the National Cerebral and Cardiovascular Center Research Institute in Japan, it is a 20-mer phosphorothioated gapmer that binds to a consensus sequence shared by human and murine PCSK9 mRNA. By inhibiting PCSK9 expression, P901SL prevents the PCSK9-mediated degradation of low-density lipoprotein receptors (LDLR) in the liver, thereby increasing hepatic LDL uptake and reducing serum LDL-cholesterol levels. In preclinical studies using hypercholesterolemic mice, P901SL demonstrated significant cholesterol-lowering effects, although it showed a delayed onset of action compared to its 2′,4′-BNA_NC-modified counterpart, P901SNC.