5′ phosphate mimics
View Patent ↗The present invention provides nucleosides and oligonucleotides comprising a 5′ phosphate mimics of formula (IVc) or (Vc). One aspect of the present invention relates to modified nucleosides and oligonucleotides comprising such dinucleotide of formula (Ia). Another aspect of the invention relates to a method of inhibiting the expression of a gene in call, the method comprising (a) contacting an oligonucleotide of the invention with the cell; and (b) maintaining the cell from step (a) for a time sufficient to obtain degradation of the mRNA of the target gene.
1. An oligonucleotide comprising a nucleoside represented by:
2. The oligonucleotide of claim 1 , wherein said oligonucleotide comprises at least one non-phosphodiester backbone linkage.
3. The oligonucleotide of claim 2 , wherein the non-phosphodiester of at least one of said non-phosphodiester backbone linkages is selected from a group consisting of phosphorothioate, phosphorodithioate, alkyl-phosphonate, and phosphoramidate.
4. The oligonucleotide of claim 2 , wherein at least one of the non-phosphodiester backbone linkages is placed between the first two nucleosides at the 5′-end and/or between the first two nucleosides at the 3′-end.
5. The oligonucleotide of claim 1 , wherein said oligonucleotide comprises at least one ligand conjugate.
6. A nucleic acid duplex comprising the oligonucleotide of claim 1 , wherein said nucleic acid duplex comprises a first strand and a second strand.
7. The nucleic acid duplex of claim 6 , wherein the nucleoside is present either in the first strand or the second strand of the nucleic acid duplex.
8. The nucleic acid duplex of claim 7 , wherein said first strand is a sense strand.
9. The nucleic acid duplex of claim 8 , wherein said second strand is an antisense strand.
10. The nucleic acid duplex of claim 6 , wherein each of said first strand and said second strand comprises said oligonucleotide.
11. The oligonucleotide of claim 1 , wherein said oligonucleotide has a hairpin structure.
12. The oligonucleotide of claim 1 , wherein said oligonucleotide is an antisense, an antagomir, a microRNA, a siRNA, a pre-microRNA, a supermir, an antimir, a ribozyme, a decoy oligonucicotidc, RNA activator, an U1 adaptor, an immunestimmulatory oligonucicotide or an aptamer.
13. The oligonucleotide of claim 12 , wherein said oligonucleotide is a single-stranded siRNA.
14. A pharmaceutical composition, comprising the oligonucleotide of claim 1 and a pharmaceutically acceptable excipient.