Antisense modulation of caspase 8 expression

Abstract

Antisense compounds, compositions and methods are provided for modulating the expression of caspase 8. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding caspase 8. Methods of using these compounds for modulation of caspase 8 expression and for treatment of diseases associated with expression of caspase 8 are provided.

What is claimed is:  
     
         1 . An antisense compound 8 to 30 nucleobases in length targeted to a nucleic acid molecule encoding caspase 8, wherein said antisense compound specifically hybridizes with and inhibits the expression of caspase 8.  
     
     
         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, 26, 28, 29, 30, 33, 35, 39, 40, 48, 49, 50, 52, 54, 58, 59, 60, 61, 62, 63, 64, 65, 68, 71, 73, 74, 75, 77, 78, 82, 84, 87, 89, 97, 98, 100, 101, 102, 103, 104, 106, 107, 108, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 133, 134, 135, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 146, 147, 148, 149, 150, 151, 152, 153, 155, 156, 157, 158, 159, 160, 161, 162, 163, 164, 165, 166, 167, 168, 169, 170, 171, 172, 173, 174 or 175.  
     
     
         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 caspase 8 in cells or tissues comprising contacting said cells or tissues with the antisense compound of  claim 1  so that expression of caspase 8 is inhibited.  
     
     
         15 . A method of treating a human having a disease or condition associated with caspase 8 comprising administering to said animal a therapeutically or prophylactically effective amount of the antisense compound of  claim 1  so that expression of caspase 8 is inhibited.  
     
     
         16 . The method of  claim 15  wherein the disease or condition is a hyperproliferative disorder.  
     
     
         17 . The method of  claim 15  wherein the disease or condition is a viral infection.  
     
     
         18 . The method of  claim 15  wherein the disease or condition is a haematopoetic disorder.  
     
     
         19 . The method of  claim 15  wherein the disease or condition is an autoimmune disorder.  
     
     
         20 . The method of  claim 15  wherein the disease or condition is AIDS.