Oligomeric compounds comprising bicyclic nucleotides and uses thereof
The present invention provides oligomeric compounds. Certain such oligomeric compounds are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell.
1. A compound comprising:
a modified oligonucleotide consisting of 19 or 20 linked nucleosides, wherein the modified oligonucleotide comprises:
a 5′-wing comprising a BABBB motif, a BBABB motif, a BABAB motif, a BBAAB motif, a BAABB motif, or a BBBAB motif, wherein the 3′-most 5′-wing nucleoside is a bicyclic nucleoside;
a 3′-wing comprising a BABBB motif, a BAABB motif, a BBAAB motif, a BABAB motif, or a BBABB motif, wherein the 5′-most 3′-wing nucleoside is a bicyclic nucleoside; and
a gap between the 5′-wing and the 3′-wing consisting of 9 or 10 linked 2′-deoxynucleosides; and
wherein each B is a bicyclic nucleoside and each A is a 2′-deoxynucleoside and the modified oligonucleotide does not comprise a non-bicyclic 2′-substituted nucleoside.
2. The compound of claim 1 , wherein the gap consists of 9 linked 2′-deoxynucleosides.
3. The compound of claim 1 , wherein the gap consists of 10 linked 2′-deoxynucleosides.
4. The compound of claim 1 , wherein the 5′ wing comprises a BABBB motif and the 3′ wing comprises a BBABB motif.
5. The compound of claim 1 , wherein the 5′ wing comprises a BBABB motif and the 3′ wing comprises a BBABB motif.
6. The compound of claim 1 , wherein the 5′ wing comprises a BBBAB motif and the 3′ wing comprises a BABAB motif.
7. The compound of claim 1 , wherein each bicyclic nucleoside is a locked nucleic acid (LNA) nucleoside.
8. The compound of claim 4 , wherein each bicyclic nucleoside is a locked nucleic acid (LNA) nucleoside.
9. The compound of claim 5 , wherein each bicyclic nucleoside is a locked nucleic acid (LNA) nucleoside.
10. The compound of claim 6 , wherein each bicyclic nucleoside is a locked nucleic acid (LNA) nucleoside.