Compounds and methods for modulating target nuclear and sub-nuclear nucleic acid molecules in cells and animals

Abstract

Compounds and methods for modulating target nucleic acids found in organelles or sub-organelles of cells are provided. The compounds and methods modulate target nucleic acids in a sub-nuclear organelle include, but are not limited to, the nucleolus and/or a cajal body of animal cells.

1 - 77 . (canceled) 
     
     
         78 . A method of reducing the amount or activity of a target sub-nuclear RNA in a cell in an animal comprising administering to the animal a pharmaceutical composition comprising an antisense compound comprising a modified oligonucleotide complementary to the target sub-nuclear RNA; and thereby reducing the amount or activity of the target sub-nuclear RNA in the cell in the animal. 
     
     
         79 . The method of  claim 78 , wherein the modified oligonucleotide comprises:
 a 5′-region consisting of 1 to 7 modified nucleosides;   a 3′-region consisting of 1 to 7 modified nucleosides; and   a central region consisting of 5 to 28 deoxyribonucleosides.   
     
     
         80 . The method of  claim 79 , wherein at least one modified nucleoside comprises a modified sugar moiety selected from among: 2′-MOE, 2′-OMe, 2′-F, LNA, ENA, cEt, and a tetrahydropyran. 
     
     
         81 . The method of  claim 78 , wherein the modified oligonucleotide comprises one or more modified internucleoside linkages. 
     
     
         82 . The method of  claim 78 , wherein the antisense compound comprises a conjugate group. 
     
     
         83 . The method of  claim 78 , wherein the target sub-nuclear RNA is a snoRNA. 
     
     
         84 . The method of  claim 78 , wherein the target sub-nuclear RNA is a scaRNA. 
     
     
         85 . The method of  claim 78 , wherein the target sub-nuclear RNA derives from a host RNA. 
     
     
         86 . The method of  claim 85 , wherein the amount and activity of the host RNA are essentially unchanged. 
     
     
         87 . The method of  claim 78 , wherein the reduced activity of the target sub-nuclear RNA results in a change in the processing of at least one object RNA. 
     
     
         88 . The method of  claim 87 , wherein the change in the processing of at least one object RNA comprises a change in the methylation of at least one object RNA. 
     
     
         89 . The method of  claim 87 , wherein the change in the processing of at least one object RNA comprises a change in polyadenylation of at least one object RNA. 
     
     
         90 . The method  claim 87 , wherein at least one object RNA is a pre-ribosomal RNA. 
     
     
         91 . The method  claim 87 , wherein at least one object RNA is an mRNA. 
     
     
         92 . The method  claim 87 , wherein at least one object RNA is a histone mRNA. 
     
     
         93 . The method  claim 78 , wherein the cell is a cancer cell. 
     
     
         94 . The method  claim 93 , wherein the administration results in a reduction of cell viability. 
     
     
         95 . The method  claim 93 , wherein the administration results in a change in cell cycling. 
     
     
         96 . The method  claim 93 , wherein the administration results in a delay in progression to S-phase. 
     
     
         97 . The method  claim 78 , wherein the animal is a human.