Antisense modulation of smad7expression

Abstract

Antisense compounds, compositions and methods are provided for modulating the expression of Smad7. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding Smad7. Methods of using these compounds for modulation of Smad7 expression and for treatment of diseases associated with expression of Smad7 are provided.

Bands are visualized using a PHOSPHORIMAGER™ (molecular dynamics, Sunnyvale Calif.).  
     
         1 . An antisense compound 8 to 30 nucleobases in length targeted to a nucleic acid molecule encoding Smad7, wherein said antisense compound specifically hybridizes with and inhibits the expression of Smad7.  
     
     
         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: 10, 12, 14, 16, 19, 24, 25, 30, 33, 35, 38, 40, 11, 18, 20, 22, 27, 31, 36, 37, 39, 41 or 42.  
     
     
         4 . The antisense compound of  claim 2  wherein the antisense oligonucleotide has a sequence comprising SEQ ID NO:10, 16, 24, 25, 30 or 40.  
     
     
         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 aniisense 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 2  wherein the antisense oligonucleotide is a chimeric oligonucleotide.  
     
     
         12 . A composition comprising the antisense compound of  claim 1  and a pharmaceutically acceptable carrier or diluent.  
     
     
         13 . The composition of  claim 12  further comprising a colloidal dispersion system.  
     
     
         14 . The composition of  claim 12  wherein the antisense compound is an antisense oligonucleotide.  
     
     
         15 . A method of inhibiting the expression of Smad7 in cells or tissues comprising contacting said cells or tissues with the antisense compound of  claim 1  so that expression of Smad7 is inhibited.  
     
     
         16 . A method of treating a human having a disease or condition associated with Smad7 comprising administering to said animal a therapeutically or prophylactically effective amount of the antisense compound of  claim 1  so that expression of Smad7 is inhibited.  
     
     
         17 . The method of  claim 16  wherein the disease or condition is a developmental disorder.  
     
     
         18 . The method of  claim 16  wherein the disease or condition is a cardiovascular disorder.  
     
     
         19 . The method of  claim 16  wherein the disease or condition is a hyperproliferative disorder.  
     
     
         20 . The method of  claim 16  wherein the disease or condition is a wound healing disorder.