Lipid compositions
Disclosed herein are lipid compositions comprising a cationic lipid of formula (I), a neutral lipid, a sterol and a PEG or PEG-modified lipid, wherein formula (I) is Also disclosed are methods of producing the cationic lipid of formula (I).
1. A lipid of formula (I):
or a salt thereof, wherein,
each X a and X b , for each occurrence, is independently C 1-6 alkylene;
1, 2, 3, 4, or 5;
A for each occurrence is NR 2 or a cyclic moiety optionally substituted with 1-3 R;
B is NR or a cyclic moiety optionally substituted with 1-2 R;
each R is independently H, alkyl,
provided that at least one R is
R 1 , for each occurrence, is independently H, R 3 ,
R 2 , for each occurrence, is independently, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, or heteroalkynyl;
R 3 , for each occurrence, is independently, alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, or heteroalkynyl;
Y, for each occurrence, is O;
R 4 , for each occurrence is independently H alkyl, alkenyl, alkynyl, heteroalkyl, heteroalkenyl, or heteroalkynyl.
2. The lipid of claim 1 , wherein n is 1 or 2.
3. The lipid of claim 1 , wherein A for each occurrence is NR 2 .
4. The lipid of claim 1 , wherein B is a cyclic moiety.
5. The lipid of claim 1 , wherein B is a nitrogen containing cyclic moiety.
6. The lipid of claim 1 , wherein B is piperidinyl or piperizinyl moiety.
7. The lipid of claim 1 , wherein each R is independently
8. The lipid of claim 1 , wherein R 1 , for each occurrence, is H.
9. The lipid of claim 1 , wherein R 2 , for each occurrence, is independently alkyl.
10. The lipid of claim 1 , wherein R 2 , for each occurrence, is independently, alkenyl.
11. The lipid of claim 1 , wherein n is 1 or 2; A is NR 2 ; B is NR or a cyclic moiety; R 1 is H; R 2 is independently alkyl or alkenyl; Y is O; and R is
12. The lipid of claim 1 , wherein n is 1; A is NR 2 ; B is a cyclic moiety; R 1 is H; R 2 is independently alkyl or alkenyl; Y is O; and R is
13. A composition, the composition comprising a sterol, a neutral lipid, a PEG or a PEG-modified lipid, and a lipid as described in claim 1 .
14. The composition of claim 13 , wherein the sterol is cholesterol.
15. The composition of claim 13 , wherein the PEG or PEG-modified lipid is a PEG-modified lipid.
16. The composition of claim 13 , wherein the composition is a liposome.
17. The composition of claim 13 , further comprising a nucleic acid agent.
18. The composition of claim 17 , wherein the nucleic acid agent is siRNA.
19. The composition of claim 17 , wherein the nucleic acid agent is mRNA.