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 medium RNA interference (RNAi) against CTNNB1 gene expression.
1. An isolated double-stranded short interfering nucleic acid (siNA) molecule that inhibits the expression of cadherin-associated protein, beta 1 (CTNNB1), wherein
(a) the siNA comprises a sense strand and an antisense strand;
(b) each strand is independently 15 to 30 nucleotides in length; and
(c) at least one strand comprises at least a 15 nucleotide sequence of SEQ ID NO:5.
2. A double-stranded short interfering nucleic acid (siNA) molecule that inhibits the expression of cadherin-associated protein, beta 1 (CTNNB1), wherein
(a) the siNA comprises a sense strand and an antisense strand;
(b) each strand is independently 15 to 30 nucleotides in length; and
(c) the antisense strand comprises at least 15 nucleotides having sequence complementary to 5′-CUGUUGGAUUGAUUCGAAA-3′ (SEQ ID NO:5).
3. A double-stranded short interfering nucleic acid (siNA) molecule that inhibits the expression of cadherin-associated protein, beta 1 (CTNNB1), wherein
(a) the siNA comprises a sense strand and an antisense strand;
(b) each strand is independently 15 to 30 nucleotides in length; and
(c) the antisense strand comprises at least a 15 nucleotide sequence of 5′-UUUCGAAUCAAUCCAACAG-3′ (SEQ ID NO:4918); and wherein one of more of the nucleotides are optionally chemically modified.
4. The double-stranded short interfering nucleic acid (siNA) molecule according to any one of claims 1 - 3 , wherein at least one nucleotide is a chemically modified nucleotide.
5. The double-stranded short interfering nucleic acid (siNA) molecule according to any one of claims 1 - 3 further comprising at least one non-nucleotide.
6. The double-stranded short interfering nucleic acid (siNA) molecule according to any one of claims 1 - 3 , wherein at least one nucleotide comprises a universal base.
7. The double-stranded short interfering nucleic acid (siNA) molecule according to any one of claims 1 - 3 , having at least one phosphorothioate internucleotide linkage.
8. The double-stranded short interfering nucleic acid (siNA) molecule according to any one of claims 1 - 3 , comprising a cap on the 3′-end, 5′-end or both 3′ and 5′ ends of at least one strand.
9. The double-stranded short interfering nucleic acid (siNA) molecule according to any one of claims 1 - 3 , comprising one or more 3′- overhang nucleotides on one or both strands.
10. The double-stranded short interfering nucleic acid (siNA) molecule of any one of claims 1 - 3 , comprising SEQ ID NOS: 6370 and 6369.
11. The double-stranded short interfering nucleic acid (siNA) molecule of any one of claims 1 - 3 , comprising SEQ ID NOS: 2021 and 2068.
12. A composition comprising the double-stranded short interfering nucleic acid (siNA) according to any one of claims 1 - 3 in a pharmaceutically acceptable carrier or diluent.
13. A composition comprising:
(a) a double-stranded short interfering nucleic acid (siNA) having SEQ ID NOS: 6370 and 6369;
(b) (13Z,16Z)-N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine;
(c) cholesterol;
(d) DSPC; and
(e) PEG-DMG.
14. A composition comprising:
(a) a double-stranded short interfering nucleic acid (siNA) having SEQ ID NOS: 2021 and 2068;
(b) (13Z,16Z)-N,N-dimethyl-3-nonyldocosa-13,16-dien-1-amine;
(c) cholesterol;
(d) DSPC; and
(e) PEG-DMG.
15. A method of treating a human subject suffering from a condition which is mediated by the action, or by loss of action, of CTNNB1, which comprises administering to said subject an effective amount of the double-stranded short interfering nucleic acid (siNA) molecule of claim 10 or 11 .