Antisense modulation of Inhibitor-kappa B Kinase-alpha expression

Abstract

Antisense compounds, compositions and methods are provided for modulating the expression of Inhibitor-kappa B Kinase-alpha. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Inhibitor-kappa B Kinase-alpha. Methods of using these compounds for modulation of Inhibitor-kappa B Kinase-alpha expression and for treatment of diseases associated with expression of Inhibitor-kappa B Kinase-alpha are provided.

What is claimed is:  
     
         1 . An antisense compound 8 to 30 nucleotides in length targeted to a nucleic acid molecule encoding human Inhibitor-kappa B Kinase-alpha, wherein said antisense compound inhibits the expression of human Inhibitor-kappa B Kinase-alpha.  
     
     
         2 . The antisense compound of  claim 1  which is an antisense oligonucleotide.  
     
     
         3 . The antisense compound of  claim 2  wherein the antisense oligonucleotide has a sequence comprising SEQ ID NO: 8, 10, 12, 14, 20, 26, 27, 34, 35, 37, 38, 43, 44 or 45.  
     
     
         4 . The antisense compound of  claim 2  wherein the antisense oligonucleotide has a sequence comprising SEQ ID NO: 12, 35 or 38.  
     
     
         5 . The antisense compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.  
     
     
         6 . The antisense compound of  claim 5  wherein the modified internucleoside linkage is a phosphorothioate linkage.  
     
     
         7 . The antisense compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified sugar moiety.  
     
     
         8 . The antisense compound of  claim 7  wherein the modified sugar moiety is a 2′-O-methoxyethyl sugar moiety.  
     
     
         9 . The antisense compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified nucleobase.  
     
     
         10 . The antisense compound of  claim 9  wherein the modified nucleobase is a 5-methylcytosine.  
     
     
         11 . The antisense compound of  claim 1  wherein the antisense oligonucleotide is a chimeric oligonucleotide.  
     
     
         12 . A pharmaceutical composition comprising the antisense compound of  claim 1  and a pharmaceutically acceptable carrier or diluent.  
     
     
         13 . The pharmaceutical composition of  claim 12  further comprising a colloidal dispersion system.  
     
     
         14 . The pharmaceutical composition of  claim 12  wherein the antisense compound is an antisense oligonucleotide.  
     
     
         15 . A method of inhibiting the expression of Inhibitor-kappa B Kinase-alpha in human cells or tissues comprising contacting said cells or tissues with the antisense compound of  claim 1  so that expression of Inhibitor-kappa B Kinase-alpha is inhibited.  
     
     
         16 . A method of treating a human having a disease or condition associated with Inhibitor-kappa B Kinase-alpha comprising administering to said animal a therapeutically or prophylactically effective amount of the antisense compound of  claim 1  so that expression of Inhibitor-kappa B Kinase-alpha is inhibited.  
     
     
         17 . The method of  claim 16  wherein the disease or condition is a hyperproliferative condition or an inflammatory condition.  
     
     
         18 . The method of  claim 17  wherein the hyperproliferative condition is cancer.  
     
     
         19 . The method of  claim 17  wherein the disease or inflammatory condition is asthma, juvenile diabetes mellitus, myasthenia gravis, Graves' disease, rheumatoid arthritis, allograft rejection, inflammatory bowel disease, multiple sclerosis, psoriasis, lupus erythematosus, systemic lupus erythematosus, diabetes, multiple sclerosis, contact dermatitis, rhinitis or various allergies.