Serum-stable amphoteric liposomes

1. A serum-stable amphoteric liposomal formulation comprising a liposome with an aqueous interior and at least one active substance in the aqueous interior, wherein the liposomes comprise 10-60 mole-% neutral lipids, 30-50 mole-% cholesterol, and, as charged lipids, either 5-30 mole-% amphoteric lipids or a maximum of 50 mole-% of a mixture of cationic and anionic lipids,

and wherein the active substance comprises at least one oligonucleotide.

2. The liposomal formulation according to claim 1 , wherein the liposomes comprise 35 to 45 mole-% cholesterol and 5 to 20 mole-% amphoteric lipids.

3. The liposomal formulation according to claim 1 , wherein the oligonucleotides comprise deoxyribonucleotides, ribonucleotide or chemically modified derivatives thereof, which are 5-100 bases in length.

4. The liposomal formulation according to claim 1 , wherein the oligonucleotides are present as single strands and/or double strands.

5. The liposomal formulation according to claim 4 , wherein the oligonucleotide is a small interfering RNA.

6. The liposomal formulation according to claim 1 , wherein the oligonucleotide is an antisense oligonucleotide.

7. The liposomal formulation according to claim 1 , wherein the oligonucleotide is an aptamer.

8. The liposomal formulation according to claim 1 , wherein the oligonucleotide is a spiegelmer.

9. The liposomal formulation according to claim 1 , wherein the liposome has a molar composition (in mole-%) selected from the group consisting of:

DMPC/MoChol/DMPS/Chol 40:10:10:40,

DMPC/AC/Chol 50:10:40,

DMPC/HisChol/DPPS/Chol 35:10:15:40,

DMPC/IsohistsuccDG/Chol 50:10:40,

DMPC/MoChol/DGSucc/Chol 35:10:15:40,

DMPC/MoChol/DGSucc/Chol 40:10:10:40,

POPC/MoChol/DGSucc/Chol 35:10:15:40,

DMPC/HistSuccDG/Chol 50:10:40,

POPC/MoChol/DPPS/Chol 40:10:10:40,

DPPC/DOTAP/DGSucc/Chol 20:10:30:40,

DPPC/HistChol/Chol 50:10:40,

DPPC/HistSuccDG/Chol 40:20:40,

DPPC/MoChol/DGSucc/Chol 20:10:30:40,

POPC/HcChol/Chol 50:15:35,

DPPC/HcChol/Chol 50:15:35,

POPC/HistPS/Chol 50:15:35,

DPPC/HistPS/Chol 50:15:35,

POPC/AC/Chol 50:15:35,

DPPC/AC/Chol 50:15:35,

DPPC/HistChol/Chol 50:15:35,

POPC/HistChol/Chol 50:15:35,

DMPC/MoChol/DGSucc/Chol 20:10:30:40,

POPC/HistSuccDG/Chol 50:15:35,

DPPC/IsoHistSuccDG/Chol 50:15:35,

DPPC/HistSuccDG/Chol 50:15:35,

POPC/IsoHistSuccDG/Chol 50:15:35,

DMPC/MoChol/DGSucc/Chol 20:10:30:40,

POPC/MoChol/CHEMS/Chol 40:10:10:40,

DMPC/HistChol/Chol 50:10:40,

POPC/DOTAP/CHEMS/Chol 30:10:20:40,

DMPC/HisChol/DGSucc/Chol 40:10:10:40,

POPC/HisChol/CHEMS/Chol 40:10:10:40,

DMPC/MoChol/CHEMS/Chol 40:10:10:40 and

POPC/MoChol/DGSucc/Chol 30:20:10:40.

10. A method of delivering an oligonucleotide to a mammal comprising administering to the mammal the oligonucleotide in the liposomal formulation of claim 1 .

11. The method of claim 10 wherein the mammal is a human.

12. The method of claim 10 wherein the liposomal formulation is administered parenterally.

13. The method of claim 10 , wherein the liposomal formulation further includes one or more active substances.

14. The liposomal formulation according to claim 1 , wherein the liposomes comprise 35 to 45 mole-% cholesterol and 15 to 45 mole-% of said mixtures of cationic and anionic lipids.

15. The liposomal formulation according to claim 1 , wherein the oligonucleotide is a decoy oligonucleotide.