UNA duplex oligomers for therapeutics
This invention provides UNA oligomers for therapeutics that can be used to modulate or reduce gene expression. The UNA oligomers can be composed of one or more 2′-3′-seco-nucleomonomers and one or more natural or non-natural nucleotide monomers, and can be a duplex having first and second strands. Embodiments include UNA oligomers with phosphorothioate or boranophosphate intermonomer linkages. The UNA oligomers can provide reduced off target effects while modulating gene expression.
1. An oligomer comprising one or more 2′-3′-seco-nucleomonomers and one or more natural or non-natural nucleotide monomers, wherein the oligomer is a duplex having first and second strands, and wherein the 2′-3′-seco-nucleomonomers are monomer D
wherein Base is a nucleobase.
2. The oligomer of claim 1 , wherein the nucleobase is adenine, thymine, uracil, guanine, cytosine, inosine, or a nucleobase of a non-natural nucleotide.
3. The oligomer of claim 1 , each strand comprising from 8 to 62 monomers in length.
4. The oligomer of claim 1 , each strand comprising from one to five 2′-3′-seco-nucleomonomers.
5. The oligomer of claim 1 , wherein one or more of the nucleotide monomers is selected from the group consisting of 2′-O-alkyl-RNA monomers, 2′-amino-DNA monomers, 2′-fluoro-DNA monomers, LNA monomers, PNA monomers, HNA monomers, ANA monomers, FANA monomers, CeNA monomers, ENA monomers, DNA monomers, and INA monomers.
6. The oligomer of claim 1 , wherein one or more of the nucleotide monomers is 2′-O-alkyl-RNA nucleotide analogues.
7. The oligomer of claim 1 , further comprising a phosphorothioate linkage or a boranophosphate linkage.
8. The oligomer of claim 1 , wherein the oligomer is capable of mediating RISC dependent translational repression or degradation of a target nucleotide sequence complementary to a portion of the oligomer.
9. The oligomer of claim 1 , wherein the oligomer is capable of mediating DICER dependent translational repression or degradation of a target nucleotide sequence complementary to a portion of the oligomer.
10. The oligomer of claim 1 , comprising a number of base pairs from 14 to 26 base pairs.
11. The oligomer of claim 1 , comprising at least one overhang.
12. The oligomer of claim 1 , comprising an overhang of from 1 to 14 monomers.
13. The oligomer of claim 1 , comprising at least one 3′-overhang.
14. The oligomer of claim 1 , comprising at least one 3′-overhang of from 1 to 14 nucleotides.
15. The oligomer of claim 1 , comprising at least one blunt end.
16. The oligomer of claim 1 , comprising a monomer sequence that is complementary to a target nucleotide sequence.
17. The oligomer of claim 16 , wherein the oligomer has reduced off-target effects as compared to an oligonucleotide having the same target nucleotide sequence, wherein the oligonucleotide is composed of only natural RNA monomers.
18. The oligomer of claim 16 , wherein the oligomer has increased or prolonged potency for gene silencing as compared to an oligonucleotide having the same target nucleotide sequence, wherein the oligonucleotide is composed of only natural RNA monomers.
19. The oligomer of claim 16 , wherein the oligomer has improved stability towards enzymatic degradation as compared to an oligonucleotide having the same target nucleotide sequence, wherein the oligonucleotide is composed of only natural RNA monomers.
20. The oligomer of claim 16 , wherein the oligomer has reduced immune stimulation as compared to an oligonucleotide having the same target nucleotide sequence, wherein the oligonucleotide is composed of only natural RNA monomers.