Cationic lipid having improved intracellular kinetics
The present invention relates to a compound represented by the formula (1) wherein X a and X b are each independently X 1 or X 2 ; s is 1 or 2, R 4 is an alkyl group having 1-6 carbon atoms, n a and n b are each independently 0 or 1, R 1a and R 1b are each independently an alkylene group having 1-6 carbon atoms, R 2a and R 2b are each independently an alkylene group having 1-6 carbon atoms, Y a and Y b are each independently an ester bond, an amide bond, a carbamate bond, an ether bond or a urea bond, and R 3a and R 3b are each independently a sterol residue, a liposoluble vitamin residue or an aliphatic hydrocarbon group having 12-22 carbon atoms, and use thereof.
1. A compound represented by the formula (1)
wherein X a and X b are each independently X 1 or X 2 ;
s is 1 or 2,
R 4 is an alkyl group having 1-6 carbon atoms,
n a and n b are each 1,
R 1a and R 1b are each independently an alkylene group having 1-6 carbon atoms,
R 2a and R 2b are each independently an alkylene group having 1-6 carbon atoms,
Y a and Y b are each independently —CO—O— or —CO—NH—, and
R 3a and R 3b are each independently a sterol residue, a liposoluble vitamin residue or an aliphatic hydrocarbon group having 12-22 carbon atoms,
wherein the sterol residue is a cholesteryl group, cholestaryl group, stigmasteryl group, β-sitosteryl group, or a lanosteryl group,
wherein the liposoluble vitamin residue is a group obtained by replacing a hydroxyl group or carboxyl group in the liposoluble vitamin with a bond, —O—CO—CH 2 —CH 2 — or —O—CO—CH 2 —CH 2 —CH 2 —, and
wherein the liposoluble vitamin is retinoic acid, retinol, ergosterol, 7-dehydrocholesterol, calciferol, cholecalciferol, dihydroergocalciferol, dihydrotachysterol, tocopherol, or tocotrienol.
2. The compound of claim 1 , wherein X a and X b are each independently X 1 .
3. The compound of claim 1 , wherein X a and X b are each independently X 2 .
4. The compound of claim 1 , wherein R 3a and R 3b are each independently a liposoluble vitamin residue or an aliphatic hydrocarbon group having 12-22 carbon atoms.
5. The compound of claim 1 , wherein R 3a and R 3b are each independently a liposoluble vitamin residue.
6. The compound of claim 1 , wherein R 3a and R 3b are each independently an aliphatic hydrocarbon group having 12-22 carbon atoms.
7. A lipid membrane structure comprising the compound of claim 1 as a membrane-constituting lipid.
8. An agent for introducing a nucleic acid, comprising the compound of claim 1 or a lipid membrane structure comprising the compound as a membrane-constituting lipid.
9. A method of introducing a nucleic acid into a cell, comprising encapsulating the nucleic acid with the lipid membrane structure of claim 7 and contacting the cell with the encapsulated nucleic acid.
10. A method of introducing a nucleic acid into a cell, comprising encapsulating the nucleic acid with the lipid membrane structure of claim 7 , and administering the encapsulated nucleic acid to a living organism to deliver the nucleic acid to the cell.
11. The compound of claim 2 , wherein R 3a and R 3b are each independently a liposoluble vitamin residue.
12. The compound of claim 2 , wherein R 3a and R 3b are each independently an aliphatic hydrocarbon group having 12-22 carbon atoms.
13. The compound of claim 3 , wherein R 3a and R 3b are each independently a liposoluble vitamin residue.
14. The compound of claim 3 , wherein R 3a and R 3b are each independently an aliphatic hydrocarbon group having 12-22 carbon atoms.
15. A lipid membrane structure comprising the compound of claim 2 as a membrane-constituting lipid.
16. A lipid membrane structure comprising the compound of claim 3 as a membrane-constituting lipid.
17. A method of introducing a nucleic acid into a cell, comprising encapsulating the nucleic acid with the lipid membrane structure of claim 15 and contacting the cell with the encapsulated nucleic acid.
18. A method of introducing a nucleic acid into a cell, comprising encapsulating the nucleic acid with the lipid membrane structure of claim 15 , and administering the encapsulated nucleic acid to a living organism to deliver the nucleic acid to the cell.
19. A method of introducing a nucleic acid into a cell, comprising encapsulating the nucleic acid with the lipid membrane structure of claim 16 and contacting the cell with the encapsulated nucleic acid.
20. A method of introducing a nucleic acid into a cell, comprising encapsulating the nucleic acid with the lipid membrane structure of claim 16 , and administering the encapsulated nucleic acid to a living organism to deliver the nucleic acid to the cell.