Antisense modulation of NF-kappa-B p65 subunit expression

Abstract

Antisense compounds, compositions and methods are provided for modulating the expression of NF-kappa-B p65 subunit. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding NF-kappa-B p65 subunit. Methods of using these compounds for modulation of NF-kappa-B p65 subunit expression and for treatment of diseases associated with expression of NF-kappa-B p65 subunit are provided.

What is claimed is:  
     
         1 . An antisense compound 8 to 30 nucleotides in length targeted to a nucleic acid molecule encoding human NF-kappa-B p65 subunit, wherein said antisense compound inhibits the expression of human NF-kappa-B p65 subunit.  
     
     
         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, 12, 13, 14, 15, 17, 20, 21, 22, 23, 24, 25, 26, 28, 30, 31, 32, 33, 34, 37, 38, 40, 41, 42, 44, 45, 46 or 47.  
     
     
         4 . The antisense compound of  claim 2  wherein the antisense oligonucleotide has a sequence comprising SEQ ID NO: 12, 23, 25, 26, 37, 40, 44 or 45.  
     
     
         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 NF-kappa-B p65 subunit in human cells or tissues comprising contacting said cells or tissues with the antisense compound of  claim 1  so that expression of NF-kappa-B p65 subunit is inhibited.  
     
     
         16 . A method of treating a human having a disease or condition associated with NF-kappa-B p65 subunit comprising administering to said animal a therapeutically or prophylactically effective amount of the antisense compound of  claim 1  so that expression of NF-kappa-B p65 subunit is inhibited.  
     
     
         17 . The method of  claim 16  wherein the disease or condition is a hyperproliferative condition or autoimmune disease or atherosclerosis.  
     
     
         18 . The method of  claim 17  wherein the hyperproliferative condition is cancer.  
     
     
         19 . The method of  claim 17  wherein the autoimmune disease is multiple sclerosis.