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 . An XIAP oligonucleotide consisting of the base sequence of SEQ ID NO:31.  
     
     
         2 . The oligonucleotide of  claim 1 , wherein said oligonucleotide comprises at least one modified internucleoside linkage.  
     
     
         3 . The oligonucleotide of  claim 2 , wherein said modified internucleoside linkage is selected from the group consisting of phosphorothioate, methylphosphonate, phosphotriester, phosphorodithioate, and phosphoselenate linkages.  
     
     
         4 . The oligonucleotide of  claim 1 , wherein said oligonucleotide comprises at least one modified sugar moiety.  
     
     
         5 . The oligonucleotide of  claim 4 , wherein said modified sugar moiety is a 2′-O methoxyethyl or a 2′-O methyl group.  
     
     
         6 . The oligonucleotide of  claim 1 , wherein said oligonucleotide is a chimeric oligonucleotide.  
     
     
         7 . The oligonucleotide of  claim 6 , wherein said chimeric oligonucleotide 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.  
     
     
         8 . The oligonucleotide of  claim 7 , 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.  
     
     
         9 . The oligonucleotide of  claim 1 , wherein the three most 5′ and the three most 3′ bases are RNA residues.  
     
     
         10 . A method of treating a patient diagnosed as having cancer, said method comprising administering to said patient an oligonucleotide consisting of the base sequence of SEQ ID NO: 31.  
     
     
         11 . The method of  claim 10 , wherein said oligonucleotide comprises at least one modified internucleoside linkage.  
     
     
         12 . The method of  claim 11 , wherein said modified internucleoside linkage is selected from the group consisting of phosphorothioate, methylphosphonate, phosphotriester, phosphorodithioate, and phosphoselenate linkages.  
     
     
         13 . The method of  claim 10 , wherein said oligonucleotide comprises at least one modified sugar moiety.  
     
     
         14 . The method of  claim 13 , wherein said modified sugar moiety is a 2′-O methoxyethyl or a 2′-O methyl group.  
     
     
         15 . The method of  claim 10 , wherein said oligonucleotide is a chimeric oligonucleotide.  
     
     
         16 . The method of  claim 15 , wherein said chimeric oligonucleotide 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.  
     
     
         17 . The method of  claim 16 , 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.  
     
     
         18 . The method of  claim 10 , wherein the three most 5′ and the three most 3′ bases are RNA residues.