Antisense modulation of glycogen synthase kinase 3 beta expression

Abstract

Antisense compounds, compositions and methods are provided for modulating the expression of glycogen synthase kinase 3 beta. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding glycogen synthase kinase 3 beta. Methods of using these compounds for modulation of glycogen synthase kinase 3 beta expression and for treatment of diseases associated with expression of glycogen synthase kinase 3 beta are provided.

What is claimed is:  
     
         1 . An antisense compound 8 to 30 nucleobases in length targeted to a nucleic acid molecule encoding glycogen synthase kinase 3 beta, wherein said antisense compound specifically hybridizes with and inhibits the expression of glycogen synthase kinase 3 beta.  
     
     
         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: 11, 12, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 58, 60, 61, 62, 63, 65, 66, 67, 68, 69, 70, 71, 72, 74, 75, 76, 78, 79, 80, 81, 82, 83, 84 or 85.  
     
     
         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 sugar 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 the modified nucleobase is a 5-methylcytosine.  
     
     
         10 . The antisense compound of  claim 2  wherein the antisense oligonucleotide is a chimeric oligonucleotide.  
     
     
         11 . A composition comprising the antisense compound of  claim 1  and a pharmaceutically acceptable carrier or diluent.  
     
     
         12 . The composition of  claim 11  further comprising a colloidal dispersion system.  
     
     
         13 . The composition of  claim 11  wherein the antisense compound is an antisense oligonucleotide.  
     
     
         14 . A method of inhibiting the expression of glycogen synthase kinase 3 beta in cells or tissues comprising contacting said cells or tissues with the antisense compound of  claim 1  so that expression of glycogen synthase kinase 3 beta is inhibited.  
     
     
         15 . A method of treating a human having a disease or condition associated with glycogen synthase kinase 3 beta comprising administering to said animal a therapeutically or prophylactically effective amount of the antisense compound of  claim 1  so that expression of glycogen synthase kinase 3 beta is inhibited.  
     
     
         16 . The method of  claim 15  wherein the disease or condition is an insulin regulation disorder.  
     
     
         17 . The method of  claim 16  wherein the insulin regulation disorder is diabetes.  
     
     
         18 . The method of  claim 15  wherein the disease or condition is a neurological disorder.  
     
     
         19 . The method of  claim 18  wherein the neurological disorder is Alzheimer's disease.  
     
     
         20 . The method of  claim 15  wherein the neurological disorder is bipolar illness.