Antisense modulation of BCL2-associated X protein expression

Abstract

Antisense compounds, compositions and methods are provided for modulating the expression of BCL2-associated X protein. The compositions comprise antisense compounds, particularly antisense oligonucleotides, targeted to nucleic acids encoding BCL2-associated X protein. Methods of using these compounds for modulation of BCL2-associated X protein expression and for treatment of diseases associated with expression of BCL2-associated X protein are provided.

What is claimed is:  
     
         1 . A compound 8 to 50 nucleobases in length targeted to a nucleic acid molecule encoding BCL2-associated X protein, wherein said compound specifically hybridizes with said nucleic acid molecule encoding BCL2-associated X protein and inhibits the expression of BCL2-associated X protein.  
     
     
         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:  23, 24, 25, 26, 28, 29, 30, 31, 33, 34, 35, 37, 39, 40, 41, 42, 43, 44, 45, 47, 48, 49, 50, 51, 52, 53, 54, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 89, 90, 91, 92, 94, 96, 97, 46, 103, 104, 105, 106, 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 121, 122, 124, 125, 126, 127, 129, 130, 131, 132, 136, 137, 138, 139, 140, 141, 142, 143, 144, 145, 147, 150, 158, 159, 160, 162, 163, 164, 165, 166, 167 or  168.  
     
     
         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 BCL2-associated X protein.  
     
     
         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 BCL2-associated X protein in cells or tissues comprising contacting said cells or tissues with the compound of  claim 1  so that expression of BCL2-associated X protein is inhibited.  
     
     
         16 . A method of treating an animal having a disease or condition associated with BCL2-associated X protein comprising administering to said animal a therapeutically or prophylactically effective amount of the compound of  claim 1  so that expression of BCL2-associated X protein is inhibited.  
     
     
         17 . The method of  claim 16  wherein the disease or condition arises from aberrant apoptosis.  
     
     
         18 . The method of  claim 16  wherein the disease or condition is familial amyotrophic lateral sclerosis, Alzeheimer's disease, Parkinson's disease, Hodgkin's disease, cartilage-hair hyperplasia, diabetes-associated ocular disorders or scrapie infections.  
     
     
         19 . The compound of  claim 1  targeted to a nucleic acid molecule encoding BCL2-associated X protein, wherein said compound specifically hybridizes with and inhibits the expression of an alternatively spliced variant of BCL2-associated X protein.  
     
     
         20 . The compound of  claim 19  wherein said alternatively spliced variant is BAX-alpha, BAX-beta, BAX-gamma, BAX-delta, BAX-omega or BAX-epsilon.