METHODS FOR MODULATING RNA USING 3' TARGETING OLIGONUCLEOTIDES
Aspects of the invention relate to methods for increasing gene expression in a targeted manner. In some embodiments, methods and compositions are provided that are useful for posttranscriptionally altering protein and/or RNA levels in a targeted manner. Aspects of the invention disclosed herein provide methods and compositions that are useful for protecting RNAs from degradation (e.g., exonuclease mediated degradation).
1 - 30 . (canceled)
31 . A method of increasing gene expression in a cell, the method comprising delivering to a cell an oligonucleotide comprising the general formula 5′-X 1 -X 2 -3′, wherein X 1 comprises 2 to 20 pyrimidine nucleotides that form base pairs with adenine; and X 2 comprises a region of complementarity that is complementary with at least 3 contiguous nucleotides of a poly-adenylated RNA transcript encoded by the gene, wherein the nucleotide at the 5′-end of the region of complementary of X 2 is complementary with the nucleotide of the RNA transcript that is immediately internal to the poly-adenylation junction of the RNA transcript.
32 . The method of claim 31 , wherein X 1 comprises 2 to 20 thymidines or uridines.
33 . The method of claim 31 , wherein the oligonucleotide comprises at least one modified internucleoside linkage.
34 . The method of claim 31 , wherein the oligonucleotide comprises at least one modified nucleotide.
35 . The method of claim 31 , wherein at least one nucleotide of the oligonucleotide comprises a 2′ O-methyl.
36 . The method of claim 31 , wherein the oligonucleotide comprises at least one ribonucleotide, at least one deoxyribonucleotide, at least one 2′-fluoro-deoxyribonucleotides or at least one bridged nucleotide.
37 . The method of claim 36 , wherein the bridged nucleotide is a LNA nucleotide, a cEt nucleotide or a ENA modified nucleotide.
38 . The method of claim 31 , wherein each nucleotide of the oligonucleotide is a LNA nucleotide.
39 . The oligonucleotide of claim 31 , wherein the nucleotides of the oligonucleotide comprise alternating deoxyribonucleotides and 2′-fluoro-deoxyribonucleotides, 2′-O-methyl nucleotides, or bridged nucleotides.
40 . The method of claim 31 , wherein the oligonucleotide is a mixmer.
41 - 142 . (canceled)
143 . The method of claim 31 , wherein the RNA transcript is an mRNA, non-coding RNA, long non-coding RNA, miRNA, snoRNA, tRNAs, snRNAs, extracellular RNAs.
144 - 155 . (canceled)