abstract |
The present disclosure provides meroduplex ribonucleic acid molecules (mdRNA) capable of decreasing or silencing PCSK9 gene expression. An mdRNA of this disclosure comprises at least three strands that combine to form at least two non-overlapping double-stranded regions separated by a nick or gap wherein one strand is complementary to a PCSK9 mRNA. In addition, the meroduplex may have at least one uridine is a 5-methyluridine, a nucleoside is a locked nucleic acid, or optionally other modifications, and any combination thereof. Also provided are methods of decreasing expression of a PCSK9 gene in a cell or in a subject to treat a PCSK9-related disease. |