Antisense modulation of MEKK4 expression
Antisense compounds, compositions and methods are provided for modulating the expression of MEKK4. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding MEKK4. Methods of using these compounds for modulation of MEKK4 expression and for treatment of diseases associated with expression of MEKK4 are provided.
1 . A compound 8 to 50 nucleobases in length targeted to a nucleic acid molecule encoding MEKK4, wherein said compound specifically hybridizes with and inhibits the expression of MEKK4.
2 . The compound of claim 1 which is an antisense oligonucleotide.
3 . The compound of claim 2 wherein the antisense oligonucleotide has a sequence comprising SEQ ID NO: 12, 13, 15, 16, 17, 22, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 38, 39, 40, 42, 43, 46, 47, 48, 49, 51, 53, 54, 56, 60, 62, 63, 64, 65, 66, 67, 68, 69, 70, 74, 76, 77, 79, 82, 84, 86, 87 or 89.
4 . The compound of claim 2 wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.
5 . The compound of claim 4 wherein the modified internucleoside linkage is a phosphorothioate linkage.
6 . The compound of claim 2 wherein the antisense oligonucleotide comprises at least one modified sugar moiety.
7 . The compound of claim 6 wherein the modified sugar moiety is a 2′-O-methoxyethyl sugar moiety.
8 . The compound of claim 2 wherein the antisense oligonucleotide comprises at least one modified nucleobase.
9 . The compound of claim 8 wherein the modified nucleobase is a 5-methylcytosine.
10 . The compound of claim 2 wherein the antisense oligonucleotide is a chimeric oligonucleotide.
11 . A compound 8 to 50 nucleobases in length which specifically hybridizes with at least an 8-nucleobase portion of an active site on a nucleic acid molecule encoding MEKK4.
12 . A composition comprising the compound of claim 1 and a pharmaceutically acceptable carrier or diluent.
13 . The composition of claim 12 further comprising a colloidal dispersion system.
14 . The composition of claim 12 wherein the compound is an antisense oligonucleotide.
15 . A method of inhibiting the expression of MEKK4 in cells or tissues comprising contacting said cells or tissues with the compound of claim 1 so that expression of MEKK4 is inhibited.
16 . A method of treating an animal having a disease or condition associated with MEKK4 comprising administering to said animal a therapeutically or prophylactically effective amount of the compound of claim 1 so that expression of MEKK4 is inhibited.
17 . The method of claim 16 wherein the disease or condition is an immunologic disorder.
18 . The method of claim 16 wherein the disease or condition is an inflammatory disorder.
19 . The method of claim 16 wherein the disease or condition is a hyperproliferative disorder.
20 . The method of claim 19 wherein the hyperproliferative disorder is cancer.