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 (CPP)-Arg peptide wherein the CPP-Arg peptide comprises the sequence as set forth in SEQ ID NO: 3.
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 , wherein the interfering RNA molecule is a siRNA, miRNA, or shRNA.
5. A pharmaceutical composition comprising the delivery system of claim 1 and a pharmaceutically acceptable carrier.
6. A method of treating an ocular disorder in a patient, comprising administering to the patient the interfering RNA delivery system of claim 1 , wherein the interfering RNA molecule can attenuate expression of a gene associated with the ocular disorder.
7. A method of delivering an interfering RNA molecule into a cell, comprising:
(a) attaching an interfering RNA molecule to a CPP-Arg peptide wherein the CPP-Arg peptide comprises the sequence as set forth in SEQ ID NO: 3, thereby forming an interfering RNA delivery system; and
(b) administering the interfering RNA delivery system to the cell under conditions suitable for the system to enter the cell.
8. The method of claim 7 , wherein release of the system from the endosome inside the cell is enhanced in the presence of an HA2 peptide.
9. The method of claim 8 , wherein the HA2 peptide is introduced into the cell by administration of a CPP-HA2 peptide.
10. The method of claim 7 , wherein the CPP-Arg peptide further comprises the HA2 peptide.
11. The method of claim 7 , wherein the interfering RNA molecule is linked to the CPP-Arg peptide via a covalent bond.
12. The method of claim 7 , wherein the interfering RNA molecule is a siRNA, miRNA, or shRNA.