IRNA agents targeting CCR5 expressing cells and uses thereof
View Patent ↗The invention relates to iRNA agents that preferably include a modification that targets CC chemokine receptor 5 (CCR5). The invention also relates to methods of making and using such modified iRNA agents.
1. A compound having structure:
wherein,
A is H, a hydroxyl protecting group, a phosphate group, an activated phosphate group, an activated phosphite group, a phosphoramidite, a solid support, a nucleotide, or an oligonucleotide;
B is H, a hydroxyl protecting group, a phosphate group, an activated phosphate group, an activated phosphate group, a phosphoramidite, a solid support, a nucleotide, or an oligonucleotide;
Z is a CCR5-binding ligand;
Q is —C(O)(CH 2 ) n NHC(O)(CH 2 ) m NH—,
—C(O)(CH 2 ) n NHC(O)(CH 2 ) m —, or —C(O)(CH 2 ) n NH—;
n is 1-20; and
m is 1-6.
2. The compound of claim 1 , wherein A is an activated phosphite group, a phosphoramidite, or a solid support.
3. The compound of claim 1 , wherein B is a hydroxyl protecting group.
4. The compound of claim 1 , wherein Q is —C(O)(CH 2 ) n NHC(O)(CH 2 ) m NH—.
5. The compound of claim 1 , wherein the CCR5-binding ligand is a CCR5 antagonist.
6. The compound of claim 5 , wherein the CCR5 antagonist is an antagonist listed in column 1 of Table 1.
7. The compound of claim 6 , wherein the CCR5 antagonist has the following structure
8. The compound of claim 6 , wherein the CCR5 antagonist has the following structure
9. The compound of claim 6 , wherein the CCR5 antagonist has the following structure
10. The compound of claim 6 , wherein the CCR5 antagonist has the following structure
11. The compound of claim 6 , wherein the CCR5 antagonist has the following structure
12. The compound of claim 6 , wherein the CCR5 antagonist has the following structure
13. The compound of claim 6 , wherein the CCR5 antagonist has the following structure
14. The compound of claim 6 , wherein the CCR5 antagonist has the following structure
15. The compound of claim 6 , wherein the CCR5 antagonist has the following structure
16. The compound of claim 6 , wherein the CCR5 antagonist has the following structure
17. The compound of claim 6 , wherein the CCR5 antagonist has the following structure
18. The compound of claim 6 , wherein the CCR5 antagonist has the following structure
19. The compound of claim 1 , wherein A is an oligonucleotide.
20. The compound of claim 19 , wherein the oligonucleotide is double stranded.
21. The compound of claim 1 , wherein B is an oligonucleotide.
22. The compound of claim 21 , wherein the oligonucleotide is double stranded.
23. The compound of claim 1 , wherein A is an oligonucleotide and B is an oligonucleotide.
24. The compound of claim 23 , wherein oligonucleotide is double stranded.