Antimicrobial agents for the dual inhibition of apolipoprotein c-iii (apoc3) and proprotein convertase subtilisin-kexin 9 (pcsk9) expression, compositions thereof, and methods of use

Abstract

RNAi agents, compositions including RNAi agents, and methods for the dual inhibition of the apolipoprotein C-III (APOC3) and proprotein convertase subtilisin-kexin 9 (PCSK9) genes are described. The APOC3-PCSK9 RNAi agents disclosed herein inhibit the expression of the APOC3 and PCSK9 genes. Pharmaceutical compositions including one or more APOC3-PCSK9 RNAi agents, optionally with one or more additional drugs, are also described. In vivo administration of the described TSLP-targeted RNAi agents to liver cells enables the inhibition of APOC3 and / or PCSK9 gene expression, which may provide a therapeutic benefit to subjects, including human subjects, for the treatment of various diseases, including hypertriglyceridemia and hypercholesterolemia.