Lipids for transfection of nucleic acids
Cationic lipid compositions are provided that are useful for efficient delivery of macromolecules, such as nucleic acids, into a wide variety of eukaryotic cell types. Methods for using the compositions also are provided.
1. A lipid having the formula III:
or a protonated form thereof,
wherein each R independently is C 1 -C 30 alkyl, alkenyl or alkanoyl;
Z3 and Z4 are independently C 1 -C 6 alkyl
R 1 and R 2 independently are selected from the group consisting of hydrogen, C 1 -C 6 alkyl, alkylamine, alkylaminoalcohol, spermiyl, spermidyl and carboxyspermiyl,
R 3 is H or C 1 -C 4 alkyl, and
R′ is H or
2. The compound according to claim 1 , wherein R′ is H.
3. The compound according to claim 1 , wherein R′ is
4. The compound according to claim 1 , wherein Z3 and Z4 are methyl.
5. The compound according to claim 1 wherein R3 is H.
6. The compound according to claim 1 , wherein each R is C 10 -C 18 alkyl or alkenyl.
7. The compound according to claim 1 wherein R1 and R2 are H.
8. The compound according to claim 1 wherein R1 and R2 are H, Z3 and Z4 are methyl, R3 is H, and each R is C 10 -C 18 alkyl or alkenyl.
9. The compound according to claim 2 wherein R1 and R2 are H, Z3 and Z4 are methyl, R3 is H, and each R is C 10 -C 18 alkyl or alkenyl.
10. A composition comprising a lipid according to claim 1 and a macromolecule.
11. The composition according to claim 10 wherein said macromolecule is a nucleic acid.
12. The composition according to claim 11 , wherein said nucleic acid comprises a DNA molecule.
13. The composition according to claim 12 , wherein said DNA molecule is a double stranded DNA molecule.
14. The composition according to claim 13 , wherein said DNA molecule is a plasmid.
15. The composition according to claim 14 , wherein said plasmid encodes an RNA molecule that is self complementary and that forms a region of double stranded RNA.
16. The composition according to claim 11 , wherein said nucleic acid comprises an RNA molecule.
17. The composition according to claim 16 , wherein said RNA molecule is a double stranded RNA molecule.
18. The composition according to claim 15 , wherein said RNA molecule is an siRNA.
19. A composition comprising a lipid according to claim 1 and a peptide or protein.
20. A kit for introducing a desired macromolecule into a cell, comprising a lipid according to claim 1 .
21. A method of introducing a nucleic acid into a cell or tissue, comprising contacting a eukaryotic cell or tissue with a composition according to claim 11 .