Lipid formulation

1. A cationic lipid of formula I:

or a pharmaceutically acceptable salt thereof.

2. A lipid formulation comprising a cationic lipid of claim 1 .

3. The lipid formulation of claim 2 , comprising 40-65% of cationic lipid of formula I, 5-10% of a neutral lipid, 25-40% of a sterol, and 0.5-10% of a PEG or PEG-modified lipid.

4. The lipid formulation of claim 3 , wherein the neutral lipid is selected from DSPC, DPPC, DMPC, POPC, DOPE and SM.

5. The lipid formulation of claim 3 , wherein the sterol is cholesterol.

6. The lipid formulation of claim 3 , wherein the PEG lipid is PEG-C 14 to PEG-C 22 , PEG-Cer 14 to PEG-C 20 , or PEG-DSPE.

7. The lipid formulation of claim 3 , wherein the formulation is prepared by an in-line mixing method.

8. The lipid formulation of claim 3 , comprising about 57.5% of cationic lipid of formula I, about 7.5% of the neutral lipid, about 31.5% of the sterol, and about 3.5% of the PEG or PEG-modified lipid.

9. The lipid formulation of claim 8 , wherein the formulation is prepared by an extrusion method.

10. The lipid formulation of claim 2 , further comprising a therapeutic agent.

11. The lipid formulation of claim 10 , wherein the therapeutic agent comprises a nucleic acid.

12. The lipid formulation of claim 11 , wherein the nucleic acid is selected from the group consisting of an siRNA, an antisense nucleic acid, a microRNA, an antimicroRNA, an antagomir, a microRNA inhibitor, a microRNA activator, an immune stimulatory nucleic acid or a Ua adaptor.

13. The lipid formulation of claim 12 , wherein the ratio of lipid:nucleic acid is about 3 to about 15.

14. The lipid formulation of claim 13 , wherein the ratio of lipid:nucleic acid about 5 to about 13.

15. The lipid formulation of claim 2 , further comprising at least one apolipoprotein.

16. The lipid formulation of claim 15 , wherein the apolipotprotein is ApoE, active polymorphic forms, isoforms, variants and mutants, and fragments or truncated forms thereof.

17. The lipid formulation of claim 2 , further comprising a targeting lipid.

18. The formulation of claim 17 , wherein the targeting lipid comprises N-acetyl galactosamine.

19. The formulation of claim 18 , wherein the N-acetyl galactosamide comprises at least a mono-, bi- or a triantennary sugar unit.

20. The formulation of claim 17 , wherein said targeting lipid is present in the formulation in a molar amount of from about 0.001% to about 5%.

21. The formulation of claim 17 , wherein said targeting lipid is the compound selected from the group consisting of Formula II, Formula III, Formula VI and Formula VII:

22. The lipid formulation of claim 3 , comprising about 50% of cationic lipid of formula I, about 10% of the neutral lipid, about 38.5% of the sterol, and about 1.5% of the PEG or PEG-modified lipid.

23. The lipid formulation of claim 3 , comprising about 50% of cationic lipid of formula I, about 10% of the neutral lipid, about 35% of the sterol, and about 5% of the PEG or PEG-modified lipid.

24. The lipid formulation of claim 3 , comprising about 57.2% of cationic lipid of formula I, about 7.1% of the neutral lipid, about 34.3% of the sterol, and about 1.4% of the PEG or PEG-modified lipid.

25. A method of delivering a therapeutic agent to a cell comprising administering to a subject the lipid formulation of claim 10 .

26. The method of claim 25 , wherein the therapeutic agent is a dsRNA.

27. The method of claim 26 , wherein the target gene is Factor VII.

28. The method of claim 26 , further comprising comparing expression of the target gene with a preselected reference value.

29. The method of claim 26 , wherein the therapeutic agent is an antisense, siRNA, ribozyme or microRNA.

30. A method of modulating the expression of a target gene in a cell, the method comprising providing to a cell the lipid formulation of claim 10 .