Antisense IAP oligonucleotides and uses thereof

Abstract

The present invention features antisense IAP oligonucleotides and other negative regulators of the IAP anti-apoptotic pathway, and methods for using them to enhance apoptosis.

1 . A nucleic acid that inhibits HIAP1 biological activity, wherein said nucleic acid consists of DNA and/or RNA residues corresponding to any one of the sequences of SEQ ID Nos: 97, 98, 99, 100, 102, 103, 104, 107, 156 and 193.  
     
     
         2 . The nucleic acid of  claim 1 , wherein said nucleic acid consists of DNA and/or RNA residues corresponding to the sequence of SEQ ID NO:97.  
     
     
         3 . The nucleic acid of  claim 1 , wherein said nucleic acid consists of DNA and/or RNA residues corresponding to the sequence of SEQ ID NO:98.  
     
     
         4 . The nucleic acid of  claim 1 , wherein said nucleic acid consists of DNA and/or RNA residues corresponding to the sequence of SEQ ID NO:99.  
     
     
         5 . The nucleic acid of  claim 1 , wherein said nucleic acid consists of DNA and/or RNA residues corresponding to the sequence of SEQ ID NO:100.  
     
     
         6 . The nucleic acid of  claim 1 , wherein said nucleic acid consists of DNA and/or RNA residues corresponding to the sequence of SEQ ID NO:102.  
     
     
         7 . The nucleic acid of  claim 1 , wherein said nucleic acid consists of DNA and/or RNA residues corresponding to the sequence of SEQ ID NO:103.  
     
     
         8 . The nucleic acid of  claim 1 , wherein said nucleic acid consists of DNA and/or RNA residues corresponding to the sequence of SEQ ID NO:104.  
     
     
         9 . The nucleic acid of  claim 1 , wherein said nucleic acid consists of DNA and/or RNA residues corresponding to the sequence of SEQ ID NO:107.  
     
     
         10 . The nucleic acid of  claim 1 , wherein said nucleic acid consists of DNA and/or RNA residues corresponding to the sequence of SEQ ID NO:156.  
     
     
         11 . The nucleic acid of  claim 1 , wherein said nucleic acid consists of DNA and/or RNA residues corresponding to the sequence of SEQ ID NO:193.  
     
     
         12 . The nucleic acid of  claim 1 , wherein the three most 5′ and the three most 3′ nucleobases are RNA residues.  
     
     
         13 . The nucleic acid of  claim 1 , wherein said HIAP1 biological activity is inhibition of apoptosis.  
     
     
         14 . The nucleic acid of  claim 1 , wherein said HIAP1 biological activity is inhibition of HIAP1 polypeptide expression.  
     
     
         15 . The nucleic acid of  claim 1 , wherein said nucleic acid comprises at least one modified internucleeoside linkage.  
     
     
         16 . The nucleic acid of  claim 15 , wherein said modified internucleioside linkage is selected from the group consisting of phosphorothioate, methylphosphonate, phosphotriester, phosphorodithioate, and phosphoselenate linkages.  
     
     
         17 . The nucleic acid of  claim 1 , wherein said nucleic acid comprises at least one modified sugar moiety.  
     
     
         18 . The nucleic acid of  claim 17 , wherein said modified sugar moiety is a 2′-O methoxyethyl or a 2′-O methyl group.  
     
     
         19 . The nucleic acid of  claim 1 , wherein said nucleic acid is a chimeric nucleic acid.  
     
     
         20 . The nucleic acid of  claim 19 , wherein said chimeric nucleic acid comprises DNA residues linked together by phosphorothioate linkages, said DNA residues flanked on each side by at least one 2′-O methoxyethyl RNA residue or 2′-O methyl RNA residue linked together by phosphorothioate linkages.  
     
     
         21 . The nucleic acid of  claim 20 , wherein said DNA residues are flanked on each side by at least three residues selected from the group consisting of 2′-O methoxyethyl RNA residues and 2′-O methyl RNA residues.  
     
     
         22 . The nucleic acid of  claim 1 , wherein said nucleic acid is a ribozyme.