Targeted compositions
The invention provides certain nucleic acids (e.g., double stranded siRNA molecules), as well as conjugates that comprise a targeting moiety, a double stranded siRNA, and optional linking groups. Certain embodiments also provide synthetic methods useful for preparing the conjugates. The conjugates are useful to target therapeutic double stranded siRNA to the liver and to treat liver diseases including hepatitis (e.g. hepatitis B and hepatitis D).
1. The compound,
or a salt thereof wherein R 2 is a siRNA molecule.
2. The compound of claim 1 , or a salt thereof, wherein the siRNA molecule is selected from the group consisting of siRNA 1 (SEQ ID NO:1 and 2), 2 (SEQ ID NO:3 and 4), 3 (SEQ ID NO:5 and 6), 4 (SEQ ID NO:7 and 8), 5 (SEQ ID NO:9 and 10), 6 (SEQ ID NO:11 and 12), 7 (SEQ ID NO:13 and 14), 8 (SEQ ID NO:15 and 16), 9 (SEQ ID NO:17 and 18), 10 (SEQ ID NO: 19 and 20), 11 (SEQ ID NO:21 and 22), 12 (SEQ ID NO:23 and 24), 13 (SEQ ID NO:25 and 26), 14 (SEQ ID NO:27 and 28), 15 (SEQ ID NO:29 and 30), 16 (SEQ ID NO:31 and 32), 17 (SEQ ID NO:33 and 34), 18 (SEQ ID NO:35 and 36), 19 (SEQ ID NO:37 and 38), 20 (SEQ ID NO:39 and 40), 21 (SEQ ID NO:41 and 42), 22 (SEQ ID NO:43 and 44), 23 (SEQ ID NO:45 and 46), 24 (SEQ ID NO:47 and 48), 25 (SEQ ID NO:49 and 50), 26 (SEQ ID NO:51 and 52), 27 (SEQ ID NO:53 and 54), 28 (SEQ ID NO:55 and 56), 29 (SEQ ID NO:57 and 58), 30 (SEQ ID NO:59 and 60), 31 (SEQ ID NO:61 and 62), 32 (SEQ ID NO:63 and 64), 33 (SEQ ID NO:65 and 66), 34 (SEQ ID NO:67 and 68), 35 (SEQ ID NO:69 and 70), 36 (SEQ ID NO:71 and 72) and 37 (SEQ ID NO:73 and 74).
3. A pharmaceutical composition comprising a compound as described in claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
4. A method to deliver a siRNA to the liver of a human comprising administering a compound as described in claim 1 , or a pharmaceutically acceptable salt thereof, to the human.
5. A method to treat a hepatitis B viral infection in a human comprising administering an effective amount of a compound as described in claim 1 , or a pharmaceutically acceptable salt thereof, to the human.
6. The compound of claim 2 , or a salt thereof, wherein the siRNA molecule is siRNA 3.
7. The compound of claim 2 , or a salt thereof, wherein the siRNA molecule is siRNA 10.
8. The compound of claim 2 , or a salt thereof, wherein the siRNA molecule is siRNA 15.
9. The compound of claim 2 , or a salt thereof, wherein the siRNA molecule is siRNA 20.
10. The compound of claim 2 , or a salt thereof, wherein the siRNA molecule is siRNA 25.
11. The compound of claim 2 , or a salt thereof, wherein the siRNA molecule is siRNA 30.
12. A pharmaceutical composition comprising the compound of claim 2 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
13. A pharmaceutical composition comprising the compound of claim 6 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
14. A pharmaceutical composition comprising the compound of claim 7 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
15. A pharmaceutical composition comprising the compound of claim 8 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
16. A pharmaceutical composition comprising the compound of claim 9 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
17. A pharmaceutical composition comprising the compound of claim 10 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.
18. A pharmaceutical composition comprising the compound of claim 11 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.