Antisense modulation of superoxide dismutase 1, soluble expression
View Patent ↗Antisense compounds, compositions and methods are provided for modulating the expression of superoxide dismutase 1, soluble. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding superoxide dismutase 1, soluble. Methods of using these compounds for modulation of superoxide dismutase 1, soluble expression and for treatment of diseases associated with expression of superoxide dismutase 1, soluble are provided.
1. A compound 20 to 50 nucleobases in length comprising the nucleobase sequence of SEQ ID NO: 98.
2. The compound of claim 1 wherein the compound is an antisense oligonucleotide.
3. The compound of claim 2 wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.
4. The compound of claim 3 wherein the modified internucleoside linkage is a phosphorothioate linkage.
5. The compound of claim 2 wherein the antisense oligonucleotide comprises at least one modified sugar moiety.
6. The compound of claim 5 wherein the modified sugar moiety is a 2′-O-methoxyethyl sugar moiety.
7. The compound of claim 2 wherein the antisense oligonucleotide comprises at least one modified nucleobase.
8. The compound of claim 7 wherein the modified nucleobase is a 5-methylcytosine.
9. The compound of claim 2 wherein the antisense oligonucleotide is a chimeric oligonucleotide.
10. A compound consisting of the nucleobase sequence of SEQ ID NO: 98.
11. The compound of claim 10 wherein the compound is an antisense oligonucleotide.
12. The compound of claim 11 wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.
13. The compound of claim 12 wherein the modified internucleoside linkage is a phosphorothioate linkage.
14. The compound of claim 11 wherein the antisense oligonucleotide comprises at least one modified sugar moiety.
15. The compound of claim 14 wherein the modified sugar moiety is a 2′-O-methoxyethyl sugar moiety.
16. The compound of claim 11 wherein the antisense oligonucleotide comprises at least one modified nucleobase.
17. The compound of claim 16 wherein the modified nucleobase is a 5-methylcytosine.
18. The compound of claim 11 wherein the antisense oligonucleotide is a chimeric oligonucleotide.
19. The compound of claim 11 wherein nucleotides 1 to 5 and 16 to 20 have a 2′-O-methoxyethyl sugar moiety, each internucleoside linkage is a phosphorothioate linkage, and each cytosine is a 5-methylcytosine.
20. A compound comprising a modified oligonucleotide consisting of 12 to 30 linked nucleosides and having a nucleobase sequence comprising at least 12 contiguous nucleobases of the nucleobase sequence set forth in SEQ ID NO: 98.
21. The compound of claim 20 , consisting of a single-stranded modified oligonucleotide.
22. The compound of claim 21 , wherein the nucleobase sequence of the modified oligonucleotide is 100% complementary to SEQ ID NO: 3.
23. The compound of claim 21 , wherein at least one internucleoside linkage is a modified internucleoside linkage.
24. The compound of claim 23 , wherein each internucleoside linkage is a phosphorothioate internucleoside linkage.
25. The compound of claim 21 , wherein at least one nucleoside comprises a modified sugar.
26. The compound of claim 25 , wherein at least one modified sugar is a bicyclic sugar.
27. The compound of claim 25 , wherein at least one modified sugar comprises a 2′-O-methoxyethyl.
28. The compound of claim 21 , wherein at least one nucleoside comprises a modified nucleobase.
29. The compound of claim 28 , wherein the modified nucleobase is a 5-methylcytosine.
30. The compound of claim 20 , wherein the modified oligonucleotide comprises:
a gap segment consisting of linked deoxynucleosides;
a 5′ wing segment consisting of linked nucleosides;
a 3′ wing segment consisting of linked nucleosides;
wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment and wherein each nucleoside of each wing segment comprises a modified sugar.
31. The compound of claim 30 , wherein the gap segment consists of ten linked nucleosides and at least one internucleoside linkage is a phosphorothioate linkage.
32. The compound of claim 21 , wherein the modified oligonucleotide consists of 20 linked nucleosides.
33. The compound of claim 32 , wherein the modified oligonucleotide comprises:
a gap segment consisting often linked deoxynucleosides;
a 5′ wing segment consisting of five linked nucleosides;
a 3′ wing segment consisting of five linked nucleosides;
wherein the gap segment is positioned between the 5′ wing segment and the 3′ wing segment wherein each nucleoside of each wing segment comprises a 2′-O-methoxyethyl sugar; and wherein at least one intemucleoside linkage is a phosphorothioate linkage.
34. The compound of claim 33 , wherein each internucleoside linkage is a phosphorotbioate linkage.