Coated lipid complexes and their use

1. A lipid composition comprising:

a nucleic acid selected from the group consisting of an RNAi, an siRNA, an siNA,

a cationic lipid component that is a compound according to formula (I),

wherein R 1 and R 2 are each independently alkyl;

n is 1-4;

R 3 is acyl selected from the group consisting of lysyl, ornithyl, 2,4-diaminobutyryl, histidyl and an acyl moiety according to formula (II),

wherein m is any integer from 1 to 3,

wherein the NH 3 + is optionally absent, and

Y − is a pharmaceutically acceptable anion,

a first helper lipid selected from a phospholipid or a steroid, and

a shielding compound comprising PEG, HEG, polyhydroxyethyl starch (polyHES) and polypropylene,

wherein said shielding compound provides for a prolonged circulation time in vivo of said lipid composition.

2. The lipid composition according to claim 1 , wherein said shielding compound is PEG2000 or PEG5000.

3. The lipid composition according to claim 1 , wherein the shielding compound is a conjugate of PEG and ceramide.

4. The lipid composition according to claim 3 , wherein the ceramide comprises at least one short carbon chain substituent of from 6 to 10 carbon atoms.

5. The lipid composition according to claim 1 , wherein said first helper lipid is ceramide, and wherein said ceramide is conjugated to PEG.

6. The lipid composition according to claim 1 , further comprising a ceramide conjugated to PEG.

7. The lipid composition according to claim 1 , wherein said shielding compound is covalently linked to said nucleic acid.

8. The lipid composition according to claim 7 , wherein the linker moiety is selected from the group consisting of an ssRNA, an ssDNA, a dsRNA, a dsDNA, a peptide, an S-S-linker and a pH sensitive linker.

9. The lipid composition according to claim 7 , wherein the nucleic acid is selected an RNAi molecule, the first strand having the following sequence:

UaAgUuCuAgCuGuGgUgG-P (SEQ ID NO: 1); and the second strand having the sequence CcAcCaCaGcUaGaAcUuA-P (SEQ ID NO: 2), whereby the modification pattern is such that the nucleotides which are capitalized are 2′-O-methyl nucleotides and P is a phosphate group.

10. The lipid composition according to claim 1 , wherein R 1 and R 2 are each independently selected from the group consisting of lauryl, myristyl, palmityl and oleyl.

11. The lipid composition according to claim 1 , wherein R 1 is lauryl and R 2 is myristyl, or R 1 is palmityl and R 2 is oleyl.

12. The lipid composition according to claim 1 , wherein m is 1 or 2.

13. The lipid composition according to claim 1 , wherein Y − is selected from the group consisting of halide, acetate and trifluoroacetate.

14. The lipid composition according to claim 1 , wherein said cationic lipid component is selected from the group consisting of:

β-arginyl-2,3-diamino propionic acid-N-palmityl-N-oleyl-amide trihydrochloride

β-arginyl-2,3-diamino propionic acid-N-lauryl-N-myristyl-amide trihydrochloride

and

ε-arginyl-lysine-N-lauryl-N-myristyl-amide trihydrochloride

15. The lipid composition according to claim 1 , further comprising a pharmaceutically acceptable carrier.