Antisense modulation of p38 mitogen activated protein kinase expression

Abstract

Compositions and methods for the treatment and diagnosis of diseases or conditions amenable to treatment through modulation of expression of a gene encoding a p38 mitogen-activated protein kinase (p38 MAPK) are provided. Methods for the treatment and diagnosis of diseases or conditions associated with aberrant expression of one or more p38 MAPKs are also provided.

What is claimed is:  
     
         1 . An antisense compound 8 to 30 nucleobases in length targeted to the 5′-untranslated region, translational start site, translational termination region or 3′-untranslated region of a nucleic acid molecule encoding a p38 mitogen activated protein kinase, wherein said antisense compound inhibits the expression of said p38 mitogen activated protein kinase.  
     
     
         2 . The antisense compound of  claim 1  which is an antisense oligonucleotide.  
     
     
         3 . The antisense compound of  claim 2  wherein the antisense oligonucleotide comprises at least an 8-nucleobase portion of SEQ ID NO: 17, 20, 38, 39, 41, 42, 43, 78, 94 or 95.  
     
     
         4 . The antisense compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.  
     
     
         5 . The antisense compound of  claim 4  wherein the modified internucleoside linkage is a phosphorothioate linkage.  
     
     
         6 . The antisense compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified sugar moiety.  
     
     
         7 . The antisense compound of  claim 6  wherein the modified sugar moiety is a 2′-O-methoxyethyl moiety.  
     
     
         8 . The antisense compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified nucleobase.  
     
     
         9 . The antisense compound of  claim 8  wherein modified nucleobase is a 5-methyl cytosine.  
     
     
         10 . The antisense compound of  claim 2  wherein the antisense oligonucleotide is a chimeric oligonucleotide.  
     
     
         11 . A pharmaceutical composition comprising the antisense compound of  claim 1  and a pharmaceutically acceptable carrier or diluent.  
     
     
         12 . The pharmaceutical composition of  claim 11  further comprising a colloidal dispersion system.  
     
     
         13 . The pharmaceutical composition of  claim 11  wherein the antisense compound is an antisense oligonucleotide.  
     
     
         14 . A method of inhibiting the expression of a p38 mitogen activated protein kinase in cells or tissues comprising contacting said cells or tissue with the antisense compound of  claim 1  so that expression of said p38 mitogen activated protein kinase is inhibited.  
     
     
         15 . A method of treating an animal having a disease or condition associated with a p38 mitogen activated protein kinase comprising administering to said animal a therapeutically or prophylactically effective amount of the antisense compound of  claim 1  so that expression of said p38 mitogen-activated protein kinase is inhibited.  
     
     
         16 . The method of  claim 15  wherein the disease or condition is an inflammatory or autoimmune disease.  
     
     
         17 . The method of  claim 16  wherein said inflammatory or autoimmune disease or condition is rheumatoid arthritis.  
     
     
         18 . The method of  claim 15  wherein said disease or condition is heart disease.  
     
     
         19 . An antisense compound 8 to 30 nucleobases in length targeted to the coding region of a nucleic acid molecule encoding a p38 mitogen-activated protein kinase, wherein said antisense compound inhibits the expression of said p38 mitogen-activated protein kinase and comprises at least an 8-nucleobase portion of SEQ ID NO. 13, 26, 27, 28, 33, 35, 37, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 97, 98, 99, 100, 101, 102, 103, 104, 105 or 106.  
     
     
         20 . The antisense compound of  claim 19  which is an antisense oligonucleotide.  
     
     
         21 . The antisense compound of  claim 20  wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.  
     
     
         22 . The antisense compound of  claim 21  wherein the modified internucleoside linkage is a phosphorothioate linkage.  
     
     
         23 . The antisense compound of  claim 20  wherein the antisense oligonucleotide comprises at least one modified sugar moiety.  
     
     
         24 . The antisense compound of  claim 23  wherein the modified sugar moiety is a 2′-O-methoxyethyl moiety.  
     
     
         25 . The antisense compound of  claim 20  wherein the antisense oligonucleotide comprises at least one modified nucleobase.  
     
     
         26 . The antisense compound of  claim 25  wherein modified nucleobase is a 5-methyl cytosine.  
     
     
         27 . The antisense compound of  claim 20  wherein the antisense oligonucleotide is a chimeric oligonucleotide.  
     
     
         28 . A pharmaceutical composition comprising the antisense compound of  claim 19  and a pharmaceutically acceptable carrier or diluent.  
     
     
         29 . The pharmaceutical composition of  claim 28  further comprising a colloidal dispersion system.  
     
     
         30 . The pharmaceutical composition of  claim 28  wherein the antisense compound is an antisense oligonucleotide.  
     
     
         31 . A method of inhibiting the expression of p38 mitogen-activated protein kinase in cells or tissues comprising contacting said cells or tissue with the antisense compound of  claim 19  so that expression of p38 mitogen-activated protein kinase is inhibited.  
     
     
         32 . A method of treating an animal having a disease or condition associated with a p38 mitogen activated protein kinase comprising administering to said animal a therapeutically or prophylactically effective amount of the antisense compound of  claim 1  so that expression of said p38 mitogen activated protein kinase is inhibited.  
     
     
         33 . The method of  claim 32  wherein the disease or condition is an inflammatory or autoimmune disease.  
     
     
         34 . The method of  claim 33  wherein said inflammatory or autoimmune disease or condition is rheumatoid arthritis.  
     
     
         35 . The method of  claim 32  wherein said disease or condition is heart disease.  
     
     
         36 . An antisense compound 8 to 30 nucleobases in length targeted to p38α mitogen activated protein kinase, wherein said antisense compound inhibits the expression of said p38α mitogen activated protein kinase and does not substantially inhibit the expression of p38β mitogen activated protein kinase.  
     
     
         37 . An antisense compound 8 to 30 nucleobases in length targeted to p38β mitogen activated protein kinase, wherein said antisense compound inhibits the expression of said p38β mitogen activated protein kinase and does not substantially inhibit the expression of p38α mitogen activated protein kinase.