Alpha-1 antitrypsin (AAT) RNAi agents, compositions including AAT RNAi agents, and methods of use
AssigneeArrowhead Pharmaceuticals, Inc.
InventorsZhen Li, Rui Zhu, Christine I. Wooddell, Tao Pei
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Abstract
RNAi agents for inhibiting the expression of the alpha-1 antitrypsin (AAT) gene, compositions including AAT RNAi agents, and methods of use are described. Also disclosed are pharmaceutical compositions including one or more AAT RNAi agents together with one or more excipients capable of delivering the RNAi agent(s) to a liver cell in vivo. Delivery of the AAT RNAi agent(s) to liver cells in vivo inhibits AAT gene expression and treats diseases associated with AAT deficiency such as chronic hepatitis, cirrhosis, hepatocellular carcinoma, transaminitis, cholestasis, fibrosis, and fulminant hepatic failure.
Claims21
An RNAi agent for inhibiting the expression of an alpha-1 antitrypsin (AAT) gene comprising a sense strand and an antisense strand,
- wherein nucleotides 2-18 of the antisense strand comprise nucleotides 2-18 of
- (SEQ ID NO:
- 83)
- NGUUAAACAUGCCUAAACN,
- wherein the sense strand is at least substantially complementary to the antisense strand;
- and
- wherein the antisense strand comprises (i) 2 or 3 phosphorothioate linkages at its 5′ end,
- (ii) at least 8 nucleotides selected from 2′-fluoro adenosine, 2′-fluoro cytidine, 2′-fluoro guanosine, and 2′-fluoro uridine, (iii) at least 11 nucleotides selected from 2′-O-methyl adenosine, 2′-O-methyl cytidine, 2′-O-methyl guanosine, and 2′-O-methyl uridine, or (iv) any combination thereof.
Dependencies are inferred from the claim text.