Antisense modulation of peroxisome proliferator-activated receptor gamma expression

Abstract

Antisense compounds, compositions and methods are provided for modulating the expression of Peroxisome proliferator-activated receptor gamma. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Peroxisome proliferator-activated receptor gamma Methods of using these compounds for modulation of Peroxisome proliferator-activated receptor gamma expression and for treatment of diseases associated with expression of Peroxisome proliferator-activated receptor gamma are provided.

1 . An antisense compound 8 to 30 nucleobases in length targeted to a nucleic acid molecule encoding Peroxisome proliferator-activated receptor gamma, wherein said antisense compound specifically hybridizes with and inhibits the expression of Peroxisome proliferator-activated receptor gamma.  
     
     
         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: 20, 28, 30, 31, 35, 49, 50, 52, 53, 57, 73, 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 Peroxisome proliferator-activated receptor gamma in cells or tissues comprising contacting said cells or tissues with the antisense compound of  claim 1  so that expression of Peroxisome proliferator-activated receptor gamma is inhibited.  
     
     
         15 . A method of treating a human having a disease or condition associated with Peroxisome proliferator-activated receptor gamma comprising administering to said animal a therapeutically or prophylactically effective amount of the antisense compound of  claim 1  so that expression of Peroxisome proliferator-activated receptor gamma is inhibited.  
     
     
         16 . The method of  claim 15  wherein the disease or condition is an inflammatory disorder.  
     
     
         17 . The method of  claim 15  wherein the disease or condition is diabetes.  
     
     
         18 . The method of  claim 15  wherein the disease or condition is a gastrointestinal 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 cardiovascular disorder.