Polymeric carrier for delivery of small interfering RNA

• US 7,740,880 B2
• Filed: 03/03/2006
• Issued: 06/22/2010
• Est. Priority Date: 03/03/2006
• Status: Expired due to Fees

• Current Assignee: University of Utah Research Foundation (State of Utah)
• Original Assignee: University of Utah Research Foundation (State of Utah)
• Inventors: Kim, Won Jong, Kim, Sung Wan
• Primary Examiner(s): EPPS -SMITH, JANET L
• Application Number:
  US11/367,228
• Publication Number:
  US 20070207966A1
• Time in Patent Office: 1,572 Days
• Field of Search: None
• US Class Current: 424/450
• CPC Class Codes: C12N 15/87 Introduction of foreign genetic material using processes not otherwise provided for, e.g. co-transformation

Abstract

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.

Claims

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:

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.

10. The method of claim 1 wherein n is about 9.

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:

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.

11. The composition of claim 7 wherein the small interfering RNA comprises siVEGF (SEQ ID NO:

1 and SEQ ID NO;

2).