Compositions and methods for the delivery of nucleic acids
A compound comprising formula (I): wherein R 1 is an akylamino 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 akyl group, an akenyl 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 nanosized complex comprising a nucleic acid and a compound comprising formula (I):
wherein R 1 is CH 2 CH 2 NH 2 ;
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 nanosized complex of claim 1 , wherein R 2 and R 3 are independently a hydrophobic group derived from oleic acid or linoleic acid.
3. The nanosized complex of claim 2 , wherein R 2 and R 3 are the same.
4. The nanosized complex 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.
5. The nanosized complex of claim 1 , wherein a, b, c, and d are each 2.
6. The nanosized complex of claim 1 , wherein the compound is
7. The nanosized complex of claim 1 , wherein polyethylene glycol is covalently attached to the compound.
8. The nanosized complex of claim 1 , wherein the targeting group is covalently attached by the linker.
9. The nanosized complex of claim 8 , wherein the linker comprises a polyamino acid group, a polyalkylene group, or a polyethylene glycol group.
10. The nanosized complex of claim 8 , wherein the targeting group comprises a peptide, a protein, an antibody, or an antibody fragment.
11. The nanosized complex of claim 9 , wherein the linker comprises an acid labile bond.
12. The nanosized complex of claim 1 , wherein the nucleic acid comprises a natural or synthetic oligonucleotide, DNA or a fragment thereof, or RNA or a fragment thereof.
13. The nanosized complex of claim 1 , wherein the nucleic acid comprises siRNA or plasmid DNA.
14. The nanosized complex of claim 1 , having an N/P ratio of at least about 6.
15. The nanosized complex of claim 1 , wherein at least one of R 4 or R 5 is a targeting group with an optional linker.
16. The nanosized complex of claim 15 , wherein the targeting group is covalently attached to the compound by the linker.
17. The nanosized complex of claim 16 , wherein the linker comprises a polyamino acid group, a polyalkylene group, or a polyethylene glycol group.
18. The nanosized complex of claim 15 , wherein the targeting group comprises a peptide, a protein, an antibody, or an antibody fragment.
19. A nanosized complex comprising a nucleic acid and a compound comprising formula (I):
wherein R 1 is CH 2 CH 2 NH 2 ;
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;
wherein the nucleic acid comprises a siRNA.
20. The nanosized complex of claim 19 , having an N/P ratio of at least about 6.
21. The nanosized complex of claim 19 , wherein R 2 and R 3 are independently a hydrophobic group derived from oleic acid or linoleic acid.
22. The nanosized complex of claim 21 , wherein R 2 and R 3 are the same.
23. The nanosized complex of claim 19 , 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.
24. The nanosized complex of claim 19 , wherein a, b, c, and d are each 2.
25. The nanosized complex of claim 19 , wherein the compound is
26. The nanosized complex of claim 19 , wherein at least one of R 4 or R 5 is a targeting group with an optional linker.
27. The nanosized complex of claim 26 , wherein the targeting group is covalently attached to the compound by the linker.
28. The nanosized complex of claim 27 , wherein the linker comprises a polyamino acid group, a polyalkylene group, or a polyethylene glycol group.
29. The nanosized complex of claim 26 , wherein the targeting group comprises a peptide, a protein, an antibody, or an antibody fragment.