Antisense modulation of matrix metalloproteinase 1 expression

Abstract

Antisense compounds, compositions and methods are provided for modulating the expression of matrix metalloproteinase 1. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding matrix metalloproteinase 1. Methods of using these compounds for modulation of matrix metalloproteinase 1 expression and for treatment of diseases associated with expression of matrix metalloproteinase 1 are provided.

1 . A compound 8 to 50 nucleobases in length targeted to a nucleic acid molecule encoding matrix metalloproteinase 1, wherein said compound specifically hybridizes with said nucleic acid molecule encoding matrix metalloproteinase 1 and inhibits the expression of matrix metalloproteinase 1.  
     
     
         2 . The compound of  claim 1  which is an antisense oligonucleotide.  
     
     
         3 . The compound of  claim 2  wherein the antisense oligonucleotide has a sequence comprising SEQ ID NO: 10, 11, 12, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 28, 29, 30, 31, 33, 38, 39, 40, 41, 43, 44, 46, 50, 51, 52, 53, 56, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 70, 72, 74, 75, 76, 77, 80, 82, 83, 84, 86, 87, 88 or 89.  
     
     
         4 . The compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.  
     
     
         5 . The compound of  claim 4  wherein the modified internucleoside linkage is a phosphorothioate linkage.  
     
     
         6 . The compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified sugar moiety.  
     
     
         7 . The compound of  claim 6  wherein the modified sugar moiety is a 2′-O-methoxyethyl sugar moiety.  
     
     
         8 . The compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified nucleobase.  
     
     
         9 . The compound of  claim 8  wherein the modified nucleobase is a 5-methylcytosine.  
     
     
         10 . The compound of  claim 2  wherein the antisense oligonucleotide is a chimeric oligonucleotide.  
     
     
         11 . A compound 8 to 50 nucleobases in length which specifically hybridizes with at least an 8-nucleobase portion of an active site on a nucleic acid molecule encoding matrix metalloproteinase 1.  
     
     
         12 . A composition comprising the 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 compound is an antisense oligonucleotide.  
     
     
         15 . A method of inhibiting the expression of matrix metalloproteinase 1 in cells or tissues comprising contacting said cells or tissues with the compound of  claim 1  so that expression of matrix metalloproteinase 1 is inhibited.  
     
     
         16 . A method of treating an animal having a disease or condition associated with matrix metalloproteinase 1 comprising administering to said animal a therapeutically or prophylactically effective amount of the compound of  claim 1  so that expression of matrix metalloproteinase 1 is inhibited.  
     
     
         17 . The method of  claim 16  wherein the disease or condition is a hyperproliferative disorder.  
     
     
         18 . The method of  claim 17  wherein the hyperproliferative disorder is cancer.  
     
     
         19 . The method of  claim 16  wherein the disease or condition is an inflammatory disorder.  
     
     
         20 . The method of  claim 16  wherein the disease or condition is atherosclerosis.