Polymeric carrier for delivery of small interfering RNA
A carrier for delivering small interfering RNA (siRNA) into cells includes a cholesterol residue covalently bonded to oligoarginine. Mixing the siRNA with the carrier produces a complex-containing composition. Contacting a cell with the complex-containing composition results in delivery of the siRNA into the cell. Delivery of an siRNA targeted to vascular endothelial growth factor is a treatment for cancer. Methods of making the carrier and complex are also disclosed.
1. A conjugate comprising a cholesterol residue covalently bonded to oligoarginine through a formate residue linker, wherein the conjugate is represented by the formula:
wherein n is about 4 to 16.
2. The composition of claim 1 wherein n is about 9.
3. The composition of claim 1 wherein the oligoarginine comprises arginine residues in the L form.
4. The composition of claim 1 wherein the oligoarginine comprises arginine residues in the D form.
5. The composition of claim 1 wherein the oligoarginine comprises arginine residues in a mixture of the L and D forms.
6. A method of making a conjugate comprising a cholesterol residue covalently bonded to oligoarginine through a formate residue linker, wherein the conjugate is represented by the formula:
wherein n is about 4 to 16, the method comprising reacting cholesterol chloroformate with oligoarginine, thereby forming an amide bond linking a cholesterol residue and the oligoarginine through the formate residue linker.
7. The method of claim 6 wherein n is about 9.
8. The method of claim 6 wherein the oligoarginine comprises arginine residues in the L form.
9. The method of claim 6 wherein the oligoarginine comprises arginine residues in the D form.
10. The method of claim 6 wherein the oligoarginine comprises arginine residues in a mixture of the L and D forms.