Antisense modulation of glycogen synthase kinase3 alpha expression

Abstract

Antisense compounds, compositions and methods are provided for modulating the expression of glycogen synthase kinase 3 alpha. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding glycogen synthase kinase 3 alpha. Methods of using these compounds for modulation of glycogen synthase kinase 3 alpha expression and for treatment of diseases associated with expression of glycogen synthase kinase 3 alpha 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 alpha, wherein said antisense compound specifically hybridizes with and inhibits the expression of glycogen synthase kinase 3 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: 12, 14, 15, 16, 17, 19, 23, 24, 27, 28, 30, 31, 32, 33, 35, 36, 38, 39, 44, 45, 47, 52, 53, 54, 55, 56, 57, 58, 61, 66, 67, 69, 74, 75, 76, 77, 78, 82, 83 or 87.  
     
     
         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 alpha 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 alpha is inhibited.  
     
     
         15 . A method of treating a human having a disease or condition associated with glycogen synthase kinase 3 alpha 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 alpha is inhibited.  
     
     
         16 . The method of  claim 15  wherein the disease or condition is diabetes.  
     
     
         17 . The method of  claim 15  wherein the disease or condition is a neurological disorder.  
     
     
         18 . The method of  claim 15  wherein the disease or condition is a haematopoetic disorder.  
     
     
         19 . The method of  claim 15  wherein the disease or condition is a hyperproliferative disorder.  
     
     
         20 . The method of  claim 15  wherein the disease or condition is a developmental disorder.