Serpinc1 iRNA compositions and methods of use thereof

摘要

The invention relates to iRNA, e.g., double-stranded ribonucleic acid (dsRNA), compositions targeting the Serpinc1 gene, and methods of using such iRNA, e.g., dsRNA, compositions to inhibit expression of Serpinc1 and methods of treating subjects having a bleeding disorder, such as a hemophilia.

主权项

1. A double-stranded ribonucleic acid (dsRNA) agent for inhibiting expression of Serpinc1, wherein said dsRNA agent comprises a sense strand and an antisense strand, the antisense strand comprising a region of complementarity which comprises at least 21 contiguous nucleotides differing by no more than 1 nucleotide from the nucleotide sequence of 5′ -UUGAAGUAAAUGGUGUUAACCAG-3′ (SEQ ID NO:562),
wherein the antisense strand comprises at least one phosphorothioate internucleoside linkage and a 3′ overhang of at least 1 nucleotide, wherein all of the nucleotides of the sense strand and all of the nucleotides of the antisense strand are modified nucleotides, wherein the nucleotide modifications are selected from the group consisting of 2′—O—methyl (2′-OMe) and 2′-fluoro nucleotide modifications, and wherein a ligand comprising an N-acetylgalactosamine (Ga1NAc) derivative is conjugated to the 3′ end of the sense strand of the dsRNA agent.