Antisense modulation of polo-like kinase expression

Abstract

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

1 . A compound 8 to 80 nucleobases in length targeted to a nucleic acid molecule encoding polo-like kinase, wherein said compound specifically hybridizes with said nucleic acid molecule encoding polo-like kinase and inhibits the expression of polo-like kinase and comprises SEQ ID NO: 18, 19, 23, 24, 25, 26, 27, 30, 31, 32, 33, 35, 37, 38, 39, 40, 41, 42, 43, 46, 47, 49, 51, 53, 55, 56, 58, 62, 63, 64, 66, 69, 70, 71, 74, 77, 79, 82, 88 or 89.  
     
     
         2 . The compound of  claim 1  which is an antisense oligonucleotide.  
     
     
         3 . The compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified internucleoside linkage.  
     
     
         4 . The compound of  claim 3  wherein the modified internucleoside linkage is a phosphorothioate linkage.  
     
     
         5 . The compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified sugar moiety.  
     
     
         6 . The compound of  claim 5  wherein the modified sugar moiety is a 2′-O-methoxyethyl sugar moiety.  
     
     
         7 . The compound of  claim 2  wherein the antisense oligonucleotide comprises at least one modified nucleobase.  
     
     
         8 . The compound of  claim 7  wherein the modified nucleobase is a 5-methylcytosine.  
     
     
         9 . The compound of  claim 2  wherein the antisense oligonucleotide is a chimeric oligonucleotide.  
     
     
         10 . A compound 8 to 80 nucleobases in length which specifically hybridizes with at least an 8-nucleobase portion of a preferred target region on a nucleic acid molecule encoding polo-like kinase.  
     
     
         11 . A composition comprising the compound of  claim 1  and a pharmaceutically acceptable carrier or diluent.  
     
     
         12 . The composition of  claim 11  further comprising a colloidal dispersion system.  
     
     
         13 . The composition of  claim 11  wherein the compound is an antisense oligonucleotide.  
     
     
         14 . A method of inhibiting the expression of polo-like kinase in cells or tissues comprising contacting said cells or tissues with the compound of  claim 1  so that expression of polo-like kinase is inhibited.  
     
     
         15 . A method of treating an animal having a disease or condition associated with polo-like kinase comprising administering to said animal a therapeutically or prophylactically effective amount of the compound of  claim 1  so that expression of polo-like kinase is inhibited.  
     
     
         16 . A method of screening for an antisense compound, the method comprising the steps of: 
 a. contacting a preferred target region of a nucleic acid molecule encoding polo-like kinase with one or more candidate antisense compounds, said candidate antisense compounds comprising at least an 8-nucleobase portion which is complementary to said preferred target region, and    b. selecting for one or more candidate antisense compounds which inhibit the expression of a nucleic acid molecule encoding polo-like kinase.    
     
     
         17 . The method of  claim 15  wherein the disease or condition is a hyperproliferative disorder.  
     
     
         18 . The method of  claim 17  wherein the hyperproliferative disorder is cancer.  
     
     
         19 . The method of  claim 18  wherein the cancer is non-small cell lung cancer.  
     
     
         20 . The method of  claim 18  wherein the cancer is esophageal carcinoma.