COMPOUNDS AND METHODS FOR MODULATING TARGET NUCLEAR AND SUB-NUCLEAR NUCLEIC ACID MOLECULES IN CELLS AND ANIMALS
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.