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 method of making a complex, the method comprising mixing a small interfering RNA with a conjugate comprising a cholesterol residue covalently bonded to oligoarginine through a formate residue linker, thereby forming the complex, wherein the conjugate is represented by the formula:
wherein n is about 4 to 16.
2. The method of claim 1 wherein the small interfering RNA is targeted to vascular endothelial growth factor.
3. The method of claim 2 wherein the small interfering RNA comprises siVEGF (SEQ ID NO:1 and SEQ ID NO:2).
4. The method of claim 1 wherein the oligoarginine comprises arginine residues, each of which is in the D form.
5. A composition comprising a mixture of a small interfering RNA and 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.
6. The composition of claim 5 wherein the arginine residues are in the D form.
7. The composition of claim 5 wherein the small interfering RNA is targeted to vascular endothelial growth factor.
8. The composition of claim 5 wherein the mixture comprises a complex of the small interfering RNA and the conjugate.
9. The composition of claim 5 wherein n is about 9.
10. The method of claim 1 wherein n is about 9.
11. The composition of claim 7 wherein the small interfering RNA comprises siVEGF (SEQ ID NO:1 and SEQ ID NO:2).