Antisense modulation of hydroxysteroid 11-beta dehydrogenase 1 expression

Abstract

Antisense compounds, compositions and methods are provided for modulating the expression of hydroxysteroid 11-beta dehydrogenase 1. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding hydroxysteroid 11-beta dehydrogenase 1. Methods of using these compounds for modulation of hydroxysteroid 11-beta dehydrogenase 1 expression and for treatment of diseases associated with expression of hydroxysteroid 11-beta dehydrogenase 1 are provided.

What is claimed is:  
     
         1 . A compound 8 to 80 nucleobases in length targeted to a nucleic acid molecule encoding hydroxysteroid 11-beta dehydrogenase 1, wherein said compound specifically hybridizes with said nucleic acid molecule encoding hydroxysteroid 11-beta dehydrogenase 1 and inhibits the expression of hydroxysteroid 11-beta dehydrogenase 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: 20, 21, 22, 25, 26, 27, 28, 30, 31, 32, 33, 34, 35, 39, 40, 41, 42, 45, 46, 47, 49, 50, 51, 52, 53, 55, 57, 58, 59, 60, 61, 64, 65, 66, 67, 68, 73, 76, 78, 80, 82, 84, 86, 88, 89, 91, 92, 94, 97, 23, 24, 36, 37, 101, 102, 103, 105, 106, 107, 108, 109, 110, 111, 112, 113, 115, 117, 118, 119, 120, 121, 122, 125, 129, 130, 131, 132, 133, 134, 135, 139, 143, 145 or 155.  
     
     
         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 80 nucleobases in length which specifically hybridizes with at least an 8-nucleobase portion of an active site on a nucleic acid molecule encoding hydroxysteroid 11-beta dehydrogenase 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 hydroxysteroid 11-beta dehydrogenase 1 in cells or tissues comprising contacting said cells or tissues with the compound of  claim 1  so that expression of hydroxysteroid 11-beta dehydrogenase 1 is inhibited.  
     
     
         16 . A method of treating an animal having a disease or condition associated with hydroxysteroid 11-beta dehydrogenase 1 comprising administering to said animal a therapeutically or prophylactically effective amount of the compound of  claim 1  so that expression of hydroxysteroid 11-beta dehydrogenase 1 is inhibited.  
     
     
         17 . The method of  claim 16  wherein the disease or condition is a metabolic disorder.  
     
     
         18 . The method of  claim 17  wherein the metabolic disorder is selected from the group consisting of obesity, diabetes, atherosclerosis and hyperlipidemia.  
     
     
         19 . The method of  claim 16  wherein the disease or condition is osteoporosis.  
     
     
         20 . The method of  claim 16  wherein the disease or condition is depression.