Compositions and methods for inhibiting expression of IKK-B gene
View Patent ↗The invention relates to a double-stranded ribonucleic acid (dsRNA) for inhibiting the expression of the IKK-B gene, comprising an antisense strand having a nucleotide sequence which is less that 30 nucleotides in length, generally 19-25 nucleotides in length, and which is substantially complementary to at least a part of the IKK-B gene. The invention also relates to a pharmaceutical composition comprising the dsRNA together with a pharmaceutically acceptable carrier; methods for treating diseases caused by the expression or activation of the IKK-B gene using the pharmaceutical composition; and methods for inhibiting the expression of the IKK-B gene in a cell.
1. A double-stranded ribonucleic acid (dsRNA) compound, comprising an antisense strand and a sense strand that are separate and each equal to or less than 30 nucleotides in length, wherein the compound is targeted to the target sequence of AL-DP-4440 (SEQ ID NO:25 and SEQ ID NO:26) within a nucleic acid molecule encoding IKK-B, and wherein the compound specifically hybridizes with the nucleic acid molecule so that expression of IKK-B is inhibited by at least 40%.
2. The dsRNA of claim 1 , wherein the dsRNA further comprises a non-nucleotide moiety.
3. The dsRNA of claim 1 , wherein the dsRNA is stabilized against nucleolytic degradation.
4. The dsRNA of claim 1 , wherein the sense strand and/or the antisense strand further comprises at least one 3′-overhang wherein the 3′-overhang comprises from 1 to 6 nucleotides.
5. The dsRNA of claim 1 , further comprising a phosphorothioate at the first internucleotide linkage at the 5′ end of the sense strand and/or the antisense strand.
6. The dsRNA of claim 1 , further comprising a phosphorothioate at the first internucleotide linkage at the 3′ end of the sense strand and/or the antisense strand.
7. The dsRNA of claim 1 , further comprising a 2′-modified nucleotide in the sense strand and/or the antisense strand.
8. The dsRNA of claim 7 , wherein the 2′-modified nucleotide comprises a modification selected from the group consisting of: 2′-deoxy, 2′-deoxy-2′-fluoro, 2′-O-methyl, 2′-O-methoxyethyl (2′-O-MOE), 2′-O-aminopropyl (2′-O-AP), 2′-O-dimethylaminoethyl (2′-O-DMAOE), 2′-O-dimethylaminopropyl (2′-O-DMAP), 2′-O-dimethylaminoethyloxyethyl (2′-O-DMAEOE), and 2′-O-N-methylacetamido (2′-O-NMA).
9. The dsRNA of claim 1 , wherein the sense strand comprises 15 or more contiguous nucleotides of the nucleotide sequence of SEQ ID NO:13.
10. The dsRNA of claim 1 , wherein the dsRNA consists of the sequences set forth in SEQ ID NO:13 and SEQ ID NO:14.
11. The dsRNA of claim 1 , wherein the antisense strand comprises 15 or more contiguous nucleotides of the nucleotide sequence of SEQ ID NO:14.
12. The dsRNA of claim 1 , wherein the sense strand comprises the sequence set forth in SEQ ID NO:25.
13. The dsRNA of claim 1 , wherein the antisense strand comprises the sequence set forth in SEQ ID NO:26.
14. The dsRNA of claim 1 , wherein the dsRNA consists of the sequences set forth in SEQ ID NO:25 and SEQ ID NO:26.
15. A vector encoding at least one of the antisense strand and the sense strand of the dsRNA of claim 1 .
16. A cell comprising the dsRNA of claim 1 .
17. A pharmaceutical composition, comprising the dsRNA of claim 1 and a pharmaceutically acceptable carrier.