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 pharmaceutical composition comprising an antisense oligonucleotide 8 to 50 nucleobases in length targeted to the 3′ untranslated region (UTR) of a nucleic acid molecule encoding human superoxide dismutase 1, soluble (SEQ ID NO: 3); wherein said oligonucleotide specifically hybridizes with and inhibits the expression of human superoxide dismutase 1, soluble (SEQ ID NO: 3) by at least 50%; and wherein said oligonucleotide comprises at least one modified internucleoside linkage.
2. The pharmaceutical composition of claim 1 , wherein said oligonucleotide is targeted to nucleobases 535-868 of SEQ ID NO: 3.
3. The pharmaceutical composition of claim 1 , wherein the modified internucleoside linkage is a phosphorothioate linkage.
4. The pharmaceutical composition of claim 1 , wherein the antisense oligonucleotide comprises at least one modified sugar moiety.
5. The pharmaceutical composition of claim 4 , wherein the modified sugar moiety is a 2′-O-methoxyethyl sugar moiety.
6. The pharmaceutical composition of claim 1 , wherein the antisense oligonucleotide comprises at least one modified nucleobase.
7. The pharmaceutical composition of claim 6 , wherein the modified nucleobase is a 5-methylcytosine.
8. The pharmaceutical composition of claim 1 , wherein the antisense oligonucleotide is a chimeric oligonucleotide.
9. The pharmaceutical composition of claim 8 , wherein the chimeric 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.
10. The pharmaceutical composition of claim 9 , wherein each nucleoside of each wing segment of said oligonucleotide comprises a modified sugar moiety.
11. The pharmaceutical composition of claim 10 , wherein the modified sugar moiety is a 2′-O-methoxyethyl sugar moiety.
12. The pharmaceutical composition of claim 9 , wherein each nucleoside of each wing segment of said oligonucleotide comprises a 2′-O-methoxyethyl sugar moiety; and wherein each internucleoside linkage of said gap segment of said oligonucleotide is a phosphorothioate linkage.
13. The pharmaceutical composition of claim 9 , wherein each nucleoside of each wing segment of said oligonucleotide comprises a 2′-O-methoxyethyl sugar moiety; and wherein each internucleoside linkage of said chimeric oligonucleotide is a phosphorothioate linkage.
14. The pharmaceutical composition of claim 1 , wherein the antisense oligonucleotide consists of 15 linked nucleosides.
15. The pharmaceutical composition of claim 1 , wherein the antisense oligonucleotide consists of 20 linked nucleosides.