RNA interference mediated inhibition of catenin (cadherin-associated protein), beta 1 (CTNNB1) 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 CTNNB1 gene expression and/or activity, and/or modulate a beta-catenin 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 CTNNB1 gene expression.
1. A double-stranded short interfering nucleic acid (siNA) molecule that inhibits the expression of cadherin-associated protein, beta 1 (CTNNB1), wherein the siNA comprises:
5′-CUGUUGGAUUGAUUCGAAA-3′ (SEQ ID NO: 5) and 5′-UUUCGAAUCAAUCCAACAG-3′ (SEQ ID NO: 4918).
2. The double-stranded short interfering nucleic acid (siNA) molecule according to claim 1 , wherein at least one nucleotide is a chemically modified nucleotide.
3. The double-stranded short interfering nucleic acid (siNA) molecule according to claim 1 further comprising at least one non-nucleotide.
4. The double-stranded short interfering nucleic acid (siNA) molecule according to claim 1 , wherein at least one nucleotide comprises a universal base.
5. The double-stranded short interfering nucleic acid (siNA) molecule according to claim 1 , having at least one phosphorothioate internucleotide linkage.
6. The double-stranded short interfering nucleic acid (siNA) molecule according to claim 1 , comprising a cap on the 3′-end, 5′-end or both 3′ and 5′ ends of at least one strand.
7. The double-stranded short interfering nucleic acid (siNA) molecule according to claim 1 , comprising one or more 3′-overhang nucleotides on one or both strands.
8. The double-stranded short interfering nucleic acid (siNA) molecule according to claim 1 , wherein the 5′ end of the antisense strand is phosphorylated.
9. The double-stranded short interfering nucleic acid (siNA) molecule of claim 7 , wherein the 3′-overhang nucleotides on at least one strand are 2′-O-methyl nucleotides.
10. The double-stranded short interfering nucleic acid (siNA) molecule of claim 9 , wherein the 2′-O-methyl nucleotides are linked with a phosphorothioate internucleotide linkage.
11. The double-stranded short interfering nucleic acid (siNA) molecule of claim 2 , wherein the chemically modified nucleotide is a 2′-deoxy-2′-fluoro nucleotide.
12. The double-stranded short interfering nucleic acid (siNA) molecule of claim 2 , wherein the chemically modified nucleotide is a 2′-deoxy nucleotide.
13. The double-stranded short interfering nucleic acid (siNA) molecule of claim 2 , wherein the chemically modified nucleotide is a 2′-O-alkyl nucleotide.
14. A double-stranded short interfering nucleic acid (siNA) molecule comprising SEQ ID NOS: 2021 and 2068.
15. A double-stranded short interfering nucleic acid (siNA) molecule comprising SEQ ID NOS: 2147 and 6368.
16. A composition comprising:
(a) the double-stranded short interfering nucleic acid (siNA) of claim 14 ;
(b) (13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine;
(c) cholesterol;
(d) DSPC; and
(e) PEG-DMG.
17. A composition comprising:
(a) the double-stranded short interfering nucleic acid (siNA) of claim 15 ;
(b) (13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine;
(c) cholesterol;
(d) DSPC; and
(e) PEG-DMG.
18. The composition according to claim 16 , wherein the (13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine, cholesterol, DSPC, and PEG-DMG have a molar ratio of 58:30:10:2, respectively.
19. The composition according to claim 16 , further comprising sucrose, trehalose, or any combination thereof.
20. The composition according to claim 17 , wherein the (13Z,16Z)—N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine, cholesterol, DSPC, and PEG-DMG have a molar ratio of 58:30:10:2, respectively.