Interfering RNA delivery system and uses thereof
View Patent ↗The invention provides a delivery system comprising a cell penetrating peptide, a polyarginine peptide, and an interfering RNA molecule. The system can be used for delivering interfering RNA molecules into a cell in vivo or in vitro. Therapeutic uses for the delivery system are also provided.
1. An interfering RNA delivery system comprising an interfering RNA molecule linked to a cell penetrating peptide-polyarginine peptide (CPP-Arg peptide), wherein the CPP comprises the amino acid of SEQ ID NO:2, and the Arg comprises SEQ ID NO:1.
2. The delivery system of claim 1 , wherein the CPP-Arg peptide further comprises an HA2 peptide.
3. The delivery system of claim 1 , wherein the interfering RNA molecule is linked to the CPP-Arg peptide via a covalent bond.
4. The delivery system of claim 1 , further comprising a pharmaceutically acceptable carrier.
5. The delivery system of claim 1 , wherein the interfering RNA molecule is an siRNA, miRNA, or shRNA.
6. The delivery system of claim 5 , wherein the interfering RNA molecule is an siRNA.
7. The delivery system of claim 1 , wherein the CPP comprises at least one D-amino acid.
8. A method of inhibiting expression of a gene in vivo comprising administering to a subject the interfering RNA delivery system of claim 1 , wherein the interfering RNA molecule attenuates expression of the gene.
9. A method of delivering an interfering RNA molecule into a cell, comprising
administering the interfering RNA delivery system of claim 1 to the cell under conditions suitable for the system to enter the cell.
10. The method of claim 9 , wherein release of the system from the endosome inside the cell is enhanced in the presence of an HA2 peptide.
11. The method of claim 9 , wherein an HA2 peptide is introduced into the cell by administration of a CPP-HA2 peptide.
12. The method of claim 9 , wherein the CPP-Arg peptide further comprises an HA2 peptide.
13. The method of claim 9 , wherein the interfering RNA molecule is linked to the CPP-Arg peptide via a covalent bond.
14. The method of claim 9 , wherein the interfering RNA molecule is a siRNA, miRNA, or shRNA.
15. The method of claim 14 , wherein the interfering RNA molecule is an siRNA.
16. The method of claim 9 , wherein the CPP comprises at least one D-amino acid.