Antisense modulation of helicase-moi expression
View Patent ↗Antisense compounds, compositions and methods are provided for modulating the expression of helicase-moi. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding helicase-moi. Methods of using these compounds for modulation of helicase-moi expression and for treatment of diseases associated with expression of helicase-moi are provided.
1. A method of decreasing helicase activity in a cell in vitro comprising:
(i) administering to said cell an antisense oligonucleotide 12 to 30 nucleobases in length targeted to nucleotides 4203-4251 of a nucleic acid molecule encoding human helicase-moi (SEQ ID NO: 3); and
(ii) detecting either a decrease in the level of human helicase-moi protein, a decrease in the level of helicase-moi mRNA, or a decrease in helicase-moi activity of said cell.
2. The method of claim 1 wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.
3. The method of claim 2 wherein the modified internucleoside linkage is a phosphorothioate linkage.
4. The method of claim 1 wherein the antisense oligonucleotide comprises at least one modified sugar moiety.
5. The method of claim 4 wherein the modified sugar moiety is a 2′-O-methoxyethyl sugar moiety.
6. The method of claim 1 wherein the antisense oligonucleotide comprises at least one modified nucleobase.
7. The method of claim 6 wherein the modified nucleobase is a 5-methylcytosine.
8. The method of claim 1 wherein the antisense oligonucleotide is a chimeric oligonucleotide.
9. The method of claim 1 wherein the antisense oligonucleotide is 100% complementary to SEQ ID NO: 3.
10. The method of claim 4 wherein the modified sugar moiety is a bicyclic sugar.
11. The method of claim 1 wherein the antisense oligonucleotide is 20 nucleobases in length.
12. The method of claim 1 wherein the antisense oligonucleotide comprises:
a gap segment consisting of linked deoxynucleosides;
a 5′ wing segment consisting of linked nucleosides; and
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.
13. The method of claim 1 wherein the antisense oligonucleotide comprises:
a gap segment consisting often linked deoxynucleosides;
a 5′ wing segment consisting of five linked nucleosides; and
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 each internucleoside linkage is a phosphorothioate linkage.