Compositions and methods for the delivery of nucleic acids
A compound comprising formula (I): wherein R 1 is an alkylamino group or a group containing at least one aromatic group; R 2 and R 3 are independently an aliphatic group or hydrophobic group; R 4 and R 5 are independently H, a substituted or unsubstituted alkyl group, an alkenyl group, an acyl group, an aromatic group, polymer, a targeting group, or a detectable moiety; a, b, c, and d are independently an integer from 1 to 10; and pharmaceutically acceptable salts thereof.
1. A compound comprising formula (I):
wherein R 1 is an alkylamino group or a group containing at least one aromatic group;
R 2 and R 3 are independently an aliphatic group or a hydrophobic group;
R 4 and R 5 are independently H, a substituted or unsubstituted alkyl group, an alkenyl group, an acyl group, an aromatic group, a substituted or unsubstituted polymer, a targeting group with an optional linker, or a detectable moiety;
a, b, c, and d are independently an integer from 1 to 10; and
pharmaceutically acceptable salts thereof.
2. The compound of claim 1 , wherein R 1 is:
where R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , and R 14 are independently hydrogen, an alkyl group, a hydrophobic group, or a nitrogen containing substituent; and
e, f, g, i, j, k, and l, are an integer from 1 to 10.
3. The compound of claim 1 , wherein R 2 and R 3 are independently a hydrophobic group derived from oleic acid or linoleic acid.
4. The compound of claim 3 , wherein R 2 and R 3 are the same.
5. The compound of claim 1 , wherein R 4 and R 5 are independently H, a substituted or unsubstituted polymer, a targeting group with an optional linker, or a detectable moiety.
6. The compound of claim 1 , wherein a, b, c, and d are each 2.
7. The compound of claim 1 , wherein R 1 is CH 2 CH 2 NH 2 , CH 2 CH 2 NHCH 2 CH 2 NHCH 2 CH 2 NH, or CH 2 CH 2 NHCH 2 CH 2 CH 2 CH 2 NHCH 2 CH 2 CH 2 NH.
8. The compound of claim 1 , wherein the compound is
9. The compound of claim 1 , wherein the linker is polyethylene glycol.
10. The compound of claim 1 , wherein the targeting group is covalently attached to the compound by a linker.
11. The compound of claim 10 , wherein the linker comprises a polyamino acid group, a polyalkylene group, or a polyethyelene glycol group.
12. The compound of claim 10 , wherein the targeting group comprises a peptide, a protein, an antibody, or an antibody fragment.
13. The compound of claim 11 , wherein the linker comprises an acid labile bond.
14. A nanosized complex comprising a nucleic acid and the compound of claim 1 .
15. The nanosized complex of claim 14 , wherein the nucleic acid comprises a natural or synthetic oligonucleotide, a DNA or fragment thereof, or an RNA or fragment thereof.
16. The nanosized complex of claim 14 , wherein the nucleic acid comprises an siRNA or plasmid DNA.
17. The nanosized complex of claim 14 , having an N/P ratio of at least about 6.
18. The nanosized complex of claim 14 , wherein at least one of R 4 and R 5 is the targeting group with the optional linker.
19. The nanosized complex of claim 18 , wherein the targeting group is covalently attached to the compound by the linker.
20. The nanosized complex of claim 19 , wherein the linker comprises a polyamino acid group, a polyalkylene group, or a polyethyelene glycol group.
21. The nanosized complex of claim 18 , wherein the targeting group comprises a peptide, a protein, an antibody, or an antibody fragment.