Post-synthetic chemical modification of RNA at the 2′-position of the ribose ring via “click” chemistry

Patent metadata

Field	Value
Publication number	US-9441228-B2
Application number	US-201514609118-A
Country	US
Kind code	B2
Filing date	Jan 29, 2015
Priority date	Jan 22, 2010
Publication date	Sep 13, 2016
Grant date	Sep 13, 2016

Abstract

This invention relates to a 2′-modified RNA agent comprising at least one RNA strand containing a 2′-O substituent having an alkyne functional group attaching to the O atom at the 2′-position on one or more ribose rings, wherein the 2′-O substituent is located at one or more of positions 2, 3, 4, 7, 8, 9, 10, 11, 13, 14, and 16, from 5′-end of the RNA strand. This invention also relates to a 2′-modified RNA agent comprising at least one RNA strand containing a 2′-O substituent having a triazole functional group attaching to the O atom at the 2′-position on one or more ribose rings, wherein the 2′-O substituent is located at one or more of positions 2, 3, 4, 7, 8, 9, 10, 11, 13, 14, and 16, from 5′-end of the RNA strand.

First claim

What is claimed is:

1. A 2′-modified siRNA, comprising at least one RNA strand containing a 2′-O substituent having an alkyne functional group at the 2′-position on one or more ribose rings, wherein the 2′-O substituent is located at one or more of positions 2, 3, 4, 7, 8, 9, 10, 11, 13, 14, and 16, from 5′-end of the RNA strand.

2. The 2′-modified siRNA of claim 1 , wherein the 2′-O substituent is located at one or more of positions 4, 9, 13, and 14.

3. The 2′-modified siRNA of claim 1 , wherein the 2′-O substituent is located at one or more of positions 7, 8, 9, and 10.

4. The 2′-modified siRNA of claim 1 , wherein the RNA strand contains a 2′-O substituent having an alkyne functional group at the 2′-position on two or more ribose rings.

5. The 2′-modified siRNA of claim 1 , wherein the siRNA is a miRNA (micro RNA).

6. The 2′-modified siRNA of claim 1 , wherein the siRNA comprises a guide (antisense) strand, and the 2′-O substituent is contained in the guide strand.

7. The 2′-modified siRNA of claim 1 , wherein the siRNA comprises a passenger (sense) strand, and the 2′-O substituent is contained in the passenger strand.

8. The 2′-modified siRNA agent of claim 1 , wherein the RNA strand has a length of about 19 to 21 nucleotides.

9. The 2′-modified RNA agent of claim 1 , wherein the alkyne functional group is a propargyl moiety attaching to the oxygen atom of the 2′-O substituent.

10. A 2′-modified siRNA, comprising at least one RNA strand containing a 2′-O substituent having a triazole functional group at the 2′-position on one or more ribose rings, wherein the 2′-O substituent is located at one or more of positions 2, 3, 4, 7, 8, 9, 10, 11, 13, 14, and 16, from 5′-end of the RNA strand.

11. The 2′-modified siRNA of claim 10 , wherein the 2′-O substituent is located at one or more of positions 4, 9, 13, and 14.

12. The 2′-modified siRNA of claim 10 , wherein the 2′-O substituent is located at one or more of positions 7, 8, 9, and 10.

13. The 2′-modified siRNA of claim 10 , wherein the RNA strand contains a 2′-O substituent having a triazole functional group at the 2′-position on two or more ribose rings.

14. The 2′-modified siRNA of claim 10 , wherein the RNA strand contains a 2′-O substituent having a triazole functional group at the 2′-position on three or more ribose rings.

15. The 2′-modified siRNA of claim 10 , wherein the siRNA comprises a guide (antisense) strand, and the 2′-O substituent is contained in the guide strand.

16. The 2′-modified siRNA of claim 10 , wherein the siRNA comprises a passenger (sense) strand, and the 2′-O substituent is contained in the passenger strand.

17. The 2′-modified siRNA of claim 10 , wherein the triazole functional group further comprises a lipid, sugar, protein, peptide, poly(ethylene)glycols, or antibody moiety.

18. The 2′-modified siRNA of claim 10 , wherein the triazole functional group further comprises benzyl or modified benzyl, ethyl-carboxymethyl, N-acetylgalactosamine, or PEG or amino-PEG.

Assignees

• Sirna Therapeutics Inc

Inventors

• Zewge Daniel
• Gosselin Francis

Classifications

• C07D211/46

  having a hydrogen atom as the second substituent in position 4 · CPC title

• C07C217/40 Primary

  having at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the same carbon atom of the carbon skeleton, e.g. amino-ketals, ortho esters · CPC title

• C07D209/48

  with oxygen atoms in positions 1 and 3, e.g. phthalimide · CPC title

• C07D207/08

  with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms · CPC title

• C07C2101/02

  Chemistry & Metallurgy · mapped topic