Antisense modulation of survivin expression

Abstract

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

1 . An antisense compound 8 to 30 nucleobases in length targeted to a nucleic acid molecule encoding human Survivin, wherein said antisense compound inhibits the expression of human Survivin.  
     
     
         2 . The antisense compound of  claim 1  which is an antisense oligonucleotide.  
     
     
         3 . The antisense compound of  claim 2  comprising at least an 8-nucleobase portion of SEQ ID NO: 19, 21, 23, 24, 25, 27, 29, 30, 32, 37, 40, 41, 43, 48, 49, 50, 51, 52, 56, 60, 65, 68, 70, 72, 76, 80, 83, 87, 88, 91, 92, 101, 106, 107, 113, 138, 141, 152 or 156.  
     
     
         4 . The antisense compound of  claim 3  comprising SEQ ID NO: 25, 30, 40, 43, 48, 65, 70, 80, 83 or 88.  
     
     
         5 . The antisense compound of  claim 2  which comprises at least one modified internucleoside linkage.  
     
     
         6 . The antisense compound of  claim 5  wherein the modified internucleoside linkage is a phosphorothioate linkage.  
     
     
         7 . The antisense compound of  claim 2  which comprises at least one modified sugar moiety.  
     
     
         8 . The antisense compound of  claim 7  wherein the modified sugar moiety is a 2′-O-methoxyethyl sugar moiety.  
     
     
         9 . The antisense compound of  claim 2  which comprises at least one modified nucleobase.  
     
     
         10 . The antisense compound of  claim 9  wherein the modified nucleobase is a 5-methylcytosine.  
     
     
         11 . The antisense compound of  claim 2  which is a chimeric oligonucleotide.  
     
     
         12 . A composition comprising the antisense 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 antisense compound is an antisense oligonucleotide.  
     
     
         15 . A method of inhibiting the expression of Survivin in human cells or tissues comprising contacting human cells or tissues with the antisense compound of  claim 1  so that expression of Survivin is inhibited.  
     
     
         16 . A method of treating an animal having a disease or condition associated with Survivin comprising administering to an animal having a disease or condition associated with Survivin a therapeutically or prophylactically effective amount of the antisense compound of  claim 1  so that expression of Survivin is inhibited.  
     
     
         17 . The method of  claim 16  wherein the disease or condition is a hyperproliferative condition.  
     
     
         18 . The method of  claim 17  wherein the hyperproliferative condition is cancer.  
     
     
         19 . A method of treating a human having a disease or condition characterized by a reduction in apoptosis comprising administering to a human having a disease or condition characterized by a reduction in apoptosis a prophylactically or therapeutically effective amount of the antisense compound of  claim 1 .  
     
     
         20 . A method of modulating apoptosis in a cell comprising contacting a cell with the antisense compound of  claim 1  so that apoptosis is modulated.  
     
     
         21 . A method of modulating cytokinesis in a cell comprising contacting a cell with the antisense compound of  claim 1  so that cytokinesis is modulated.  
     
     
         22 . A method of modulating the cell cycle in a cell comprising contacting a cell with the antisense compound of  claim 1  so that the cell cycle is modulated.  
     
     
         23 . A method of inhibiting the proliferation of cells comprising contacting cells with an effective amount of the antisense compound of  claim 1 , so that proliferation of the cells is inhibited.  
     
     
         24 . The method of  claim 23  wherein said cells are cancer cells.  
     
     
         25 . The composition of  claim 12  further comprising a chemotherapeutic agent.  
     
     
         26 . The method of  claim 19  further comprising administering to the patient a chemotherapeutic agent.  
     
     
         27 . The method of  claim 20  wherein said modulation of apoptosis is sensitization to an apoptotic stimulus.  
     
     
         28 . The method of  claim 27  wherein said apoptotic stimulus is a cytotoxic chemotherapeutic agent.  
     
     
         29 . The method of  claim 23  further comprising contacting said cells with a chemotherapeutic agent.  
     
     
         30 . The method of  claim 29  wherein said chemotherapeutic agent is taxol or cisplatin.