RNA interference mediated inhibition of interleukin and interleukin receptor gene expression using short interfering nucleic acid (siNA)
This invention relates to compounds, compositions, and methods useful for modulating interleukin and/or interleukin receptor gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of interleukin and/or interleukin receptor gene expression and/or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features 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 and methods used to modulate the expression of interleukin and/or interleukin receptor genes.
1. A chemically modified nucleic acid molecule, wherein:
(a) the nucleic acid molecule comprises a sense strand having SEQ ID NO:1715 and a separate antisense strand having SEQ ID NO: 1723
(b) 50 percent or more of the nucleotides in each strand comprise a 2′-sugar modification, wherein the 2′-sugar modification of any of the pyrimidine nucleotides differs from the 2′-sugar modification of any of the purine nucleotides.
2. The nucleic acid molecule of claim 1 , wherein the 2′-sugar modification of any of the purine nucleotides in the sense strand differs from the 2′-sugar modification of any of the purine nucleotides in the antisense strand.
3. The nucleic acid molecule of claim 1 , wherein the 2′-sugar modification is selected from the group consisting of 2′-deoxy-2′-fluoro, 2′-O-methyl, and 2′-deoxy.
4. The nucleic acid of claim 3 , wherein the 2′-deoxy-2′-fluoro sugar modification is a pyrimidine modification.
5. The nucleic acid of claim 3 , wherein the 2′-deoxy sugar modification is a pyrimidine modification.
6. The nucleic acid of claim 3 , wherein the 2′-O-methyl sugar modification is a pyrimidine modification.
7. The nucleic acid molecule of claim 4 , wherein said pyrimidine modification is in the sense strand, the antisense strand, or both the sense strand and antisense strand.
8. The nucleic acid molecule of claim 6 , wherein said pyrimidine modification is in the sense strand, the antisense strand, or both the sense strand and antisense strand.
9. The nucleic acid molecule of claim 3 , wherein the 2′-deoxy sugar modification is a purine modification.
10. The nucleic acid molecule of claim 3 , wherein the 2′-O-methyl sugar modification is a purine modification.
11. The nucleic acid molecule of claim 9 , wherein the purine modification is in the sense strand.
12. The nucleic acid molecule of claim 10 , wherein the purine modification is in the antisense strand.
13. The nucleic acid molecule of claim 1 , wherein the nucleic acid molecule comprises ribonucleotides.
14. The nucleic acid molecule of claim 1 , wherein the sense strand includes a terminal cap moiety at the 5′-end, the 3′-end, or both of the 5′- and 3′-ends.
15. The nucleic acid molecule of claim 14 , wherein the terminal cap moiety is an inverted deoxy abasic moiety.
16. The nucleic acid molecule of claim 1 , wherein said nucleic acid molecule includes one or more phosphorothioate internucleotide linkages.
17. The nucleic acid molecule of claim 16 , wherein one of the phosphorothioate internucleotide linkages is at the 3′-end of the antisense strand.
18. The nucleic acid molecule of claim 1 , wherein the 5′-end of the antisense strand includes a terminal phosphate group.
19. A composition comprising the nucleic acid molecule of claim 1 , in a pharmaceutically acceptable carrier or diluent.