Oligomeric compounds and compositions for the use in modulation of target nucleic acids
View Patent ↗Compounds, compositions and methods are provided for modulating the levels expression, processing and function of miRNAs. The compositions comprise oligomeric compounds targeted to small non-coding RNAs and miRNAs. The oligomeric compounds possess potent miRNA inhibitory activity, and further exhibit improved therapeutic index. Further provided are methods for selectively modulating miRNA activing in a cell.
1. A single-stranded oligomeric compound comprising a contiguous sequence of 17 to 29 nucleosides linked by internucleoside linking groups, said sequence having an internal region located between two external regions, each external region independently comprises from 1 to 3 nucleosides, each external region comprises only 2′-O(CH 2 ) 2 OCH 3 modified nucleosides, and the internal region comprises only β-D-2′-deoxy-2′-fluororibofuranosyl nucleosides, wherein the compound is complementary to a nucleic acid target that is not a miRNA.
2. The oligomeric compound of claim 1 , where at least one internucleoside linkage group is a phosphorothioate internucleoside linkage group.
3. The oligomeric compound of claim 1 , wherein each internucleoside linkage group is a phosphorothioate internucleoside linkage group.
4. The oligomeric compound of claim 1 , wherein each external region consists of 2 nucleosides and the internal region consists of 19 nucleosides.
5. The oligomeric compound of claim 1 , wherein each external region consists of 2 nucleosides and the internal region consists of 18 nucleosides.
6. The oligomeric compound of claim 1 , wherein each external region consists of 2 nucleosides and the internal region consists of 17 nucleosides.
7. The oligomeric compound of claim 1 , wherein each external region comprises 2 or 3 nucleosides.
8. The oligomeric compound of claim 1 , wherein a first external region comprises 1 or 2 nucleosides and a second external region comprises 2 to 3 nucleosides.
9. The oligomeric compound of claim 1 , wherein the compound is an alternate splicer.