METHODS FOR SELECTIVE TARGETING OF HETEROCHROMATIN FORMING NON-CODING RNA
Provided herein are oligonucleotides that are useful for modulating the heterochromatin state of genes; related compositions and methods are also provided. In some embodiments, methods are provided for treating a disease associated with heterochromatin formation, including diseases associated with repeat expansion within genes.
1 .- 53 . (canceled)
54 . A method for increasing expression of a target gene in cells, the method comprising:
delivering to the cells an oligonucleotide complementary to a heterochromatin forming non-coding RNA associated with the target gene, wherein the oligonucleotide comprises a region of complementarity that is complementary with a position adjacent to a repeat region of the heterochromatin forming non-coding RNA.
55 . The method of claim 54 , wherein the oligonucleotide further comprises a region of complementarity that is complementary with a position within the repeat region of the heterochromatin forming non-coding RNA.
56 . The method of claim 54 , wherein the oligonucleotide is a cleavage promoting oligonucleotide.
57 . The method of claim 54 , wherein the RNA is a long non-coding RNA (lncRNA).
58 . The method of claim 57 , wherein the lncRNA is antisense to the gene.
59 . The method of claim 54 , wherein the repeat region comprises triplet repeats.
60 . The method of claim 54 , wherein the oligonucleotide comprises a region of complementarity that is complementary with a position within 5 kb from an end of the repeat region.
61 . The method of claim 54 , wherein the oligonucleotide is single stranded.
62 . The method of claim 61 , wherein the oligonucleotide comprises at least one modified nucleotide.
63 . The method of claim 62 , wherein the modified nucleotide is a bridged nucleotide.
64 . The method of claim 63 , wherein the bridge nucleotide is a locked nucleic acid (LNA) nucleotide, a constrained ethyl (cEt) nucleotide, or an ethylene bridged nucleic acid (ENA) nucleotide.
65 . The method of claim 62 , wherein the modified nucleotide is 2′ O-methyl nucleotide.
66 . The method of claim 56 , wherein the oligonucleotide is a gapmer.