UNA oligomers targeting micro-RNA for therapeutics
This invention provides UNA oligomers for therapeutics that can be used to target micro-RNAs. 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 single stranded oligomer. Embodiments include UNA oligomers with phosphorothioate or boranophosphate intermonomer linkages. The UNA oligomers can be used to target micro-RNAs to reduce micro-RNA activity.
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 single-stranded RNA targeting a microRNA, 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 , comprising from 8 to 62 monomers in length.
4. The oligomer of claim 1 , 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 , comprising a monomer sequence that is complementary to a target nucleotide sequence.
9. The oligomer of claim 1 , wherein the oligomer has increased or prolonged potency as compared to an oligonucleotide having the same target nucleotide sequence, wherein the oligonucleotide is composed of only natural RNA monomers.