Modulation of survivin expression

Abstract

Compounds and compositions are provided for modulating the expression of survivin. The compounds, exemplified by those acting through an RNAi antisense mechanism of action, include double-stranded and single-stranded constructs, as well as siRNAs, canonical siRNAs, blunt-ended siRNAs and single-stranded antisense RNA compounds. Methods of using these compounds for modulation of survivin expression and for treatment of diseases associated with expression of survivin are provided.

1 - 71 . (canceled) 
     
     
         72 . A compound comprising a chemically modified or unmodified doublestranded nucleic acid compound that is 19-23 nucleobases in length,
 wherein a first strand has at least 19 contiguous nucleobases of a polynucleotide selected from the group consisting of SEQ ID NOs: 17, 23, 25, 27, 29, 31, 35, 37, 39, 41, 43, 45, 47, 49, 51, 53, 55, 59, 61, 65, 67, 69, 73, and 81,
 and wherein a second strand is 100% complementary to the first strand. 
   
     
     
         73 . The compound of  claim 72  which is blunt-ended or canonical. 
     
     
         74 . The compound of  claim 72  comprising at least one chemical modification to a sugar, nucleobase, or internucleoside linkage. 
     
     
         75 . The compound of  claim 74  wherein each chemical modification to the sugar is a 2′ modification. 
     
     
         76 . The compound of  claim 75  wherein each 2′ sugar modification is independently selected from the group consisting of 2′-O-methoxyethyl (2′-MOE), 2′-O-methyl, locked nucleic acid (LNA) and 2′-fluoro. 
     
     
         77 . The compound of  claim 76  wherein each 2′ modification is a 2′-O-methoxyethyl (2′-MOE). 
     
     
         78 . The compound of  claim 76  wherein each 2′ modification is a 2′-O-methyl. 
     
     
         79 . The compound of  claim 76  wherein each 2′ modification is a 2′-fluoro. 
     
     
         80 . The compound of  claim 76  wherein each 2′ modification of the sugar results in a bicyclic sugar. 
     
     
         81 . The compound of  claim 80  wherein the bicyclic modification is a locked nucleic acid (LNA). 
     
     
         82 . The compound of  claim 74  wherein the chemical modification to the sugar is a 4′ thio. 
     
     
         83 . The compound of  claim 75  comprising two or more chemically distinct 2′ sugar modifications. 
     
     
         84 . The compound of  claim 74  comprising at least one internucleoside linkage modification. 
     
     
         85 . The compound of  claim 84  comprising mixed phosphorothioate and phosphodiester linkages. 
     
     
         86 . The compound of  claim 85  comprising alternating phosphorothioate and phosphorodiester internucleoside linkages. 
     
     
         87 . The compound of  claim 76  comprising at least one internucleoside linkage modification. 
     
     
         88 . The compound of  claim 87  comprising mixed phosphorothioate and phosphodiester linkages. 
     
     
         89 . The compound of  claim 88  comprising alternating phosphorothioate and phosphorodiester internucleoside linkages. 
     
     
         90 . The compound of  claim 72  comprising a conjugate. 
     
     
         91 . The compound of  claim 72  wherein the first strand consists of SEQ ID NO:81. 
     
     
         92 . The compound of  claim 91  wherein the compound is canonical. 
     
     
         93 . A pharmaceutical composition comprising the compound of  claim 72  and a pharmaceutically acceptable carrier or diluent. 
     
     
         94 . A method for treating a condition associated with survivin expression or overexpression comprising administering to an animal, particularly a human, an effective amount of a compound of  claim 72 . 
     
     
         95 . The method of  claim 94  wherein the condition is cancer. 
     
     
         96 . The method of  claim 95  wherein the cancer is selected from the group consisting of hepatocellular cancer, breast cancer, colon cancer, prostate cancer, lung cancer, bladder cancer, ovarian cancer, renal cancer, glioblastoma, pancreatic cancer and non-Hodgkin's lymphoma.