RNA interference mediated inhibition of hepatitis B Virus (HBV) gene expression using short interfering nucleic acid (siNA)
View Patent ↗The present invention relates to compounds, compositions, and methods for the study, diagnosis, and treatment of traits, diseases and conditions that respond to the modulation of HBV gene expression and/or activity, and/or modulate a HBV gene expression pathway. Specifically, the invention relates to double-stranded nucleic acid molecules including small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules that are capable of mediating or that mediate RNA interference (RNAi) against HBV gene expression.
1. A double-stranded short interfering nucleic acid (siNA) molecule comprising a sense strand comprising the nucleotide sequence 5′-B gCCgaUCCaUaCUgCggaaUsU B-3′ (SEQ ID NO:326) and an antisense strand comprising the nucleotide sequence 5′-UUCCgCagUaUggaUCggCUsU-3′ (SEQ ID NO:225), wherein B is an inverted abasic moiety, bolded nucleotides comprise 2′-O-methyl modifications, lower case nucleotides comprise 2′-fluoro modifications, italicized nucleotides are deoxynucleotides, and s is a phosphorothioate linkage.
2. A composition comprising the double-stranded short interfering nucleic acid (siNA) according to claim 1 and a pharmaceutically acceptable carrier or diluent.
3. A composition comprising:
(a) the double-stranded short interfering nucleic acid (siNA) of claim 1 ;
(b) a cationic lipid;
(c) cholesterol;
(d) DSPC; and
(e) PEG-DMG.
4. A composition comprising:
(a) the double-stranded short interfering nucleic acid (siNA) of claim 1 ;
(b) (13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine;
(c) cholesterol;
(d) DSPC; and
(e) PEG-DMG.
5. The composition according to claim 4 , wherein the (13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine, cholesterol, DSPC, and PEG-DMG have a molar ratio of 50:30:10:2 respectively.
6. A composition comprising the composition according to claim 5 and a pharmaceutically acceptable carrier or diluent.
7. A method of treating a human subject suffering from a condition which is mediated by the action, or by loss of action, of Hepatitis B Virus (HBV), which comprises administering to said subject an effective amount of the double-stranded short interfering nucleic acid (siNA) molecule of claim 1 .
8. The method according to claim 7 , wherein the condition is HBV infection.
9. The method according to claim 7 , wherein the condition is hepatocellular carcinoma.
10. A kit comprising the double-stranded short interfering nucleic acid (siNA) according to claim 1 .