UNA oligomers for therapeutics
This invention is directed to oligomers composed of 2′-3′-seco-nucleomonomers and nucleotides or modified nucleotides, wherein the oligomer can be a microRNA and include from one to five 2′-3′-seco-nucleomonomers. The oligomers can have a sequence that is complementary to a target nucleotide sequence and be used for affecting the regulation of gene expression. Among other things, the oligomers can provide reduced off target effects.
1. An oligomer comprising an acyclic 2′-3′-seco-nucleomonomer, wherein the oligomer is a microRNA, wherein the oligomer comprises from one to five acyclic monomers, and wherein the acyclic monomer is monomer D
wherein Base is a nucleobase.
2. The oligomer of claim 1 , further comprising a nucleotide analogue selected from the group consisting of 2′-O-alkyl-RNA monomers, 2′-amino-DNA monomers, 2′-fluoro-DNA monomers, PNA monomers, HNA monomers, ANA monomers, FANA monomers, CeNA monomers, ENA monomers, DNA monomers, and INA monomers.
3. The oligomer of claim 1 , further comprising one or more 2′-O-alkyl-RNA nucleotide analogues.
4. The oligomer of claim 1 , further comprising a phosphorothioate linkage or a boranophosphate linkage.
5. The oligomer of claim 1 , wherein the oligomer has a sequence that is complementary to a target nucleotide sequence.
6. The oligomer of claim 1 , wherein the oligomer has reduced off-target effects as compared to an oligonucleotide having the same sequence with natural RNA monomers instead of acyclic monomers.
7. The oligomer of claim 1 , wherein the oligomer has increased or prolonged potency for gene silencing as compared to an oligonucleotide having the same sequence with natural RNA monomers instead of acyclic monomers.
8. The oligomer of claim 1 , wherein the oligomer has improved stability towards enzymatic degradation as compared to an oligonucleotide having the same sequence with natural RNA monomers instead of acyclic monomers.
9. The oligomer of claim 1 , wherein the oligomer has reduced immune stimulation as compared to an oligonucleotide having the same sequence with natural RNA monomers instead of acyclic monomers.