Antisense modulation of C-reactive protein expression
View Patent ↗Antisense compounds, compositions and methods are provided for modulating the expression of C-reactive protein. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding C-reactive protein. Methods of using these compounds for modulation of C-reactive protein expression and for treatment of diseases associated with expression of C-reactive protein are provided.
1. A composition comprising an oligomeric compound 12 to 30 nucleobases in length that specifically hybridizes with SEQ ID NO:3, wherein said compound comprises at least an 8-nucleobase portion of SEQ ID NO: 28, and wherein said compound inhibits the expression of C-reactive protein, and a pharmaceutically acceptable carrier or diluent.
2. The composition of claim 1 further comprising a colloidal dispersion system.
3. The composition of claim 1 wherein the oligomeric compound is an oligonucleotide.
4. The composition of claim 3 , wherein the oligonucleotide comprises at least one modified internucleoside linkage.
5. The composition of claim 4 wherein the modified internucleoside linkage is a phosphorothioate linkage.
6. The composition of claim 3 wherein the oligonucleotide comprises at least one modified sugar moiety.
7. The composition of claim 6 wherein the modified sugar moiety is a 2′-O-methoxyethyl sugar moiety.
8. The composition of claim 3 wherein the oligonucleotide comprises at least one modified nucleobase.
9. The composition of claim 8 wherein the modified nucleobase is a 5-methylcytosine.
10. The composition of claim 3 wherein the oligonucleotide is a chimeric oligonucleotide.
11. An oligomeric compound 12 to 30 nucleobases in length that is 100% complementary to SEQ ID NO:3, wherein said oligomeric compound comprises at least an 8-nucleobase portion of SEQ ID NO: 28, and wherein said oligomeric compound inhibits the expression of C-reactive protein.
12. The oligomeric compound of claim 11 wherein the compound is an oligonucleotide.
13. The oligomeric compound of claim 12 , wherein the oligonucleotide comprises at least one modified internucleoside linkage.
14. The oligomeric compound of claim 13 wherein the modified internucleoside linkage is a phosphorothioate linkage.
15. The oligomeric compound of claim 12 wherein all of the internucleoside linkages of the oligonucleotide are phosphorothioate linkages.
16. An oligonucleotide 12 to 30 nucleobases in length that specifically hybridizes with SEQ ID NO:3, wherein said oligonucleotide comprises at least an 8-nucleobase portion of SEQ ID NO: 28, and comprises at least one modified sugar moiety, and wherein said oligonucleotide inhibits the expression of C-reactive protein.
17. The oligonucleotide of claim 16 wherein the modified sugar moiety is a 2′-O-methoxyethyl sugar moiety.
18. An oligonucleotide 12 to 30 nucleobases in length that specifically hybridizes with SEQ ID NO:3, wherein said oligonucleotide comprises at least an 8-nucleobase portion of SEQ ID NO: 28 and comprises at least one modified nucleobase, and wherein said oligonucleotide inhibits the expression of C-reactive protein.
19. The oligonucleotide of claim 18 wherein the modified nucleobase is a 5-methylcytosine.
20. The oligomeric compound of claim 15 wherein the oligonucleotide is a chimeric oligonucleotide.
21. The oligomeric compound of claim 20 wherein the chimeric oligonucleotide is a gapmer.
22. The oligomeric compound of claim 21 wherein the gapmer comprises:
a 5′ wing segment;
a 3′ wing segment; and
a gap segment positioned between said 5′ wing segment and said 3′ wing segment.
23. The oligomeric compound of claim 22 wherein each of said 5′ wing segment and 3′ wing segment comprise at least one 2′-O-methoxyethyl sugar moiety.
24. An oligomeric compound 20 nucleobases in length that specifically hybridizes with SEQ ID NO:3, wherein said oligomeric compound comprises at least an 8-nucleobase portion of SEQ ID NO: 28, wherein said oligomeric compound inhibits the expression of C-reactive protein.
25. The composition of claim 1 , wherein said oligomeric compound comprises at least a 12 nucleobase portion of SEQ ID NO:28.
26. The composition of claim 1 , wherein said oligomeric compound is 100% complementary to SEQ ID NO:3.
27. An oligomeric compound 12 to 30 nucleobases in length that is 100% complementary to SEQ ID NO:3, wherein said oligomeric compound comprises at least a 12-nucleobase portion of SEQ ID NO: 28, and wherein said oligomeric compound inhibits the expression of C-reactive protein.
28. The composition of claim 6 wherein the modified sugar moiety is a bicyclic sugar moiety.
29. The oligonucleotide of claim 16 wherein the modified sugar moiety is a bicyclic sugar moiety.
30. The composition of claim 25 , wherein the oligomeric compound comprises the nucleobase sequence of SEQ ID NO:28.
31. The oligomeric compound of claim 27 , wherein the oligomeric compound comprises the nucleobase sequence of SEQ ID NO:28.
32. The composition of claim 1 , wherein said oligomeric compound is single-stranded.
33. The oligomeric compound of claim 11 , wherein said oligomeric compound is single-stranded.
34. The composition of claim 26 further comprising a colloidal dispersion system.
35. The composition of claim 26 wherein the oligomeric compound is an oligonucleotide.
36. The composition of claim 35 , wherein the oligonucleotide comprises at least one modified internucleoside linkage.
37. The composition of claim 35 wherein the modified internucleoside linkage is a phosphorothioate linkage.
38. The composition of claim 36 , wherein all of the internucleoside linkages of the oligonucleotide are phosphorothioate linkages.
39. The composition of claim 35 wherein the oligonucleotide comprises at least one modified sugar moiety.
40. The composition of claim 39 , wherein the modified sugar moiety is a bicyclic sugar moiety.
41. The composition of claim 39 wherein the modified sugar moiety is a 2′-O-methoxyethyl sugar moiety.
42. The composition of claim 35 wherein the oligonucleotide comprises at least one modified nucleobase.
43. The composition of claim 42 wherein the modified nucleobase is a 5-methlcytosine.
44. The composition of claim 35 wherein the oligonucleotide is a chimeric oligonucleotide.
45. The composition of claim 44 , wherein the chimeric oligonucleotide is a gapmer.
46. The oligomeric compound of claim 45 wherein the gapmer comprises:
a 5′ wing segment;
a 3′ wing segment; and
a gap segment positioned between said 5′ wing segment and said 3′ wing segment.
47. The composition of claim 46 wherein each of said 5′ wing segment and 3′ wing segment comprise at least one 2′-O-methoxyethyl sugar moiety.
48. The composition of claim 26 wherein said oligomeric compound is 20 nucleotides in length.