PSEUDOCIRCULARIZATION OLIGONUCLEOTIDES FOR MODULATING RNA
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 - 72 . (canceled)
73 . An oligonucleotide comprising the general formula 5′-X 1 —X 2 -3′, wherein X 1 comprises 5 to 20 nucleotides that have a region of complementarity that is complementary with at least 5 contiguous nucleotides of an RNA transcript encoded by a gene in the cell, wherein the nucleotide at the 3′-end of the region of complementary of X 1 is complementary with the nucleotide at the transcription start site of the RNA transcript, wherein X 2 comprises a region of complementarity that is complementary with at least 5 contiguous nucleotides of the RNA transcript that do not overlap the region of the RNA transcript that is complementary with the region of complementarity of X 1 .
74 . The oligonucleotide of claim 73 , wherein the region of complementarity of X 2 is within 100 nucleotides of a polyadenylation junction of the RNA transcript.
75 . The oligonucleotide of claim 74 , wherein the region of complementarity of X 2 is complementary with the RNA transcript immediately adjacent to or overlapping the polyadenylation junction of the RNA transcript.
76 . The oligonucleotide of claim 74 , wherein X 2 further comprises at least 2 consecutive pyrimidine nucleotides complementary with adenine nucleotides of the poly(A) tail of the RNA transcript.
77 . The oligonucleotide of claim 73 , wherein the RNA transcript is an mRNA, non-coding RNA, long non-coding RNA, miRNA, or snoRNA.
78 - 89 . (canceled)
90 . The oligonucleotide of claim 73 , wherein the oligonucleotide is 10 to 50 nucleotide in length.
91 - 93 . (canceled)
94 . The oligonucleotide of claim 73 , wherein the oligonucleotide comprises at least one modified internucleoside linkage.
95 . The oligonucleotide of claim 73 , wherein the oligonucleotide comprises at least one modified nucleotide.
96 . The oligonucleotide of claim 73 , wherein at least one nucleotide comprises a 2′ O-methyl.
97 . The oligonucleotide of claim 73 , wherein the oligonucleotide comprises at least one ribonucleotide, at least one deoxyribonucleotide, at least one 2′-fluoro-deoxyribonucleotides or at least one bridged nucleotide.
98 . The oligonucleotide of claim 97 , wherein the bridged nucleotide is a LNA nucleotide, a cEt nucleotide or a ENA modified nucleotide.
99 . The oligonucleotide of claim 73 , wherein each nucleotide of the oligonucleotide is a LNA nucleotide.
100 . The oligonucleotide of claim 73 , wherein the nucleotides of the oligonucleotide comprise alternating deoxyribonucleotides and 2′-fluoro-deoxyribonucleotides, 2′-O-methyl nucleotides, or bridged nucleotides.
101 . The oligonucleotide of claim 73 , wherein the oligonucleotide is mixmer.
102 - 108 . (canceled)
109 . A composition comprising a plurality of oligonucleotides, wherein each of at least 75% of the oligonucleotides is an oligonucleotide of claim 73 .
110 - 114 . (canceled)
118 . A pharmaceutical composition comprising an oligonucleotide of claim 73 and a pharmaceutically acceptable carrier.
119 - 155 . (canceled)