Inhibitory oligonucleotides targeted to BCL-2

Abstract

Inhibitory oligonucleotides are disclosed which are targeted to three specific target regions and subsequences of the target regions found on nucleic acids encoding Bcl-2. These inhibitory oligonucleotides are generally of from about 8 to about 50 nucleotides in length. Specific preferred oligonucleotides are disclosed. The oligonucleotides of the invention may be incorporated into compositions such as pharmaceutical compositions, and may be used in methods for inhibiting the expression of Bcl-2 in a cell or tissue, methods for treating conditions susceptible to modulation of Bcl-2 expression in an organism, and methods for detecting nucleic acid encoding BCL-2.

1 . An isolated oligonucleotide comprising a sequence of at least 8 contiguous nucleobases which is substantially identical or complementary to at least a portion of SEQ ID NO: 19 or SEQ ID NO: 19 wherein U is substituted for T.  
     
     
         2 . The oligonucleotide of  claim 1  wherein the sequence is substantially identical or complementary to SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 14, SEQ ID NO: 22, SEQ ID NO: 23, SEQ ID NO: 24, SEQ ID NO: 25 or an any of the foregoing SEQ ID NOs. wherein U is substituted for T.  
     
     
         3 . The oligonucleotide of  claim 1  wherein the substantially identical or complementary sequence is about 10-26 nucleobases in length.  
     
     
         4 . The oligonucleotide of  claim 1  which is an RNA oligonucleotide.  
     
     
         5 . The oligonucleotide of  claim 1  which comprises a non-naturally occurring nucleobase, sugar or internucleotide linkage.  
     
     
         6 . The oligonucleotide of  claim 5  which comprises a phosphorothioate internucleotide linkage.  
     
     
         7 . A composition comprising the oligonucleotide of  claim 1  and a pharmaceutically acceptable carrier, diluent or adjuvant.