Antisense modulation of transforming growth factor-beta expression

Abstract

Compositions and methods are provided for inhibiting the expression of TGF-β2. Antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding TGF-β2 are preferred. Methods of using these compounds for modulation of TGF-β2 expression and for treatment of diseases associated with expression of TGF-β are also provided.

What is claimed is:  
     
         1 . A compound 8 to 50 nucleobases in length targeted to a nucleic acid molecule encoding TGF-β2, wherein said compound comprises at least a portion of a sequence selected from the group consisting of SEQ ID NO:53, 54, 55, 56, 58, 60, 61, 62, 63, 64, 65, 66 or 69, and wherein said compound modulates the expression of TGF-β2.  
     
     
         2 . The compound of  claim 1  which is an antisense oligonucleotide.  
     
     
         3 . The compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.  
     
     
         4 . The compound of  claim 3  wherein the modified internucleoside linkage of the antisense oligonucleotide is a phosphorothioate linkage.  
     
     
         5 . The compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified sugar moiety.  
     
     
         6 . The compound of  claim 5  wherein the modified sugar moiety of the antisense oligonucleotide is a 2′-O-methoxyethyl sugar moiety.  
     
     
         7 . The compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified nucleobase.  
     
     
         8 . The compound of  claim 7  wherein the modified nucleobase of the antisense oligonucleotide is a 5-methylcytosine.  
     
     
         9 . The compound of  claim 2  wherein the antisense oligonucleotide is a chimeric oligonucleotide.  
     
     
         10 . A composition comprising the compound of  claim 1  and a pharmaceutically acceptable carrier or diluent.  
     
     
         11 . The composition of  claim 10  further comprising a colloidal dispersion system.  
     
     
         12 . The composition of  claim 10  wherein the compound is an antisense oligonucleotide.  
     
     
         13 . A method of inhibiting the expression of TGF-β2 in cells or tissues comprising contacting said cells or tissues with the compound of  claim 1  so that expression of TGF-β2 is inhibited.  
     
     
         14 . A method of treating an animal having a disease or condition associated with TGF-β2 comprising administering to said animal a therapeutically or prophylactically effective amount of the compound of  claim 1  so that expression of TGF-β2 is inhibited.  
     
     
         15 . The method of  claim 14  wherein said disease or condition is inflammation.  
     
     
         16 . The method of  claim 14  wherein said disease or condition is fibrosis or a fibrotic disease or condition.  
     
     
         17 . The method of  claim 16 , wherein said fibrotic disease or condition is fibrotic scarring, peritoneal adhesions, lung fibrosis or conjunctival scarring.