P900SL

P900SL is a 2',4'-bridged nucleic acid (BNA)-modified antisense oligonucleotide (AON) designed to target murine proprotein convertase subtilisin/kexin type 9 (PCSK9) mRNA. By binding to the PCSK9 transcript, P900SL induces its degradation, thereby reducing the levels of secreted PCSK9 protein. This reduction prevents PCSK9-mediated degradation of the low-density lipoprotein receptor (LDLR) in the liver, leading to increased hepatic uptake of LDL from the bloodstream and a subsequent reduction in serum LDL-cholesterol (LDL-C) levels. Research has also indicated that P900SL-mediated inhibition of PCSK9 may upregulate CYP7A1, the rate-limiting enzyme in bile acid synthesis, providing an additional mechanism for cholesterol homeostasis. P900SL was developed as a research tool to evaluate the efficacy and toxicological profile of BNA-based antisense therapies for the treatment of hypercholesterolemia.