Interfering rna delivery system and uses thereof

Abstract

The invention provides a delivery system comprising a cell penetrating peptide, 10 histidines, 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.

What is claimed is: 
     
         1 . An interfering RNA delivery system comprising an interfering RNA molecule linked to a YM3-1 OH peptide. 
     
     
         2 . The delivery system of  claim 1 , wherein the interfering RNA molecule is linked to the YM3-1 OH peptide via a covalent bond. 
     
     
         3 . The delivery system of  claim 1 , wherein the YM3-10H peptide comprises: 
       
         
           
                 
                 
                 
               
                     
                   CHHHHHTHRLPRRRRRRHHHHHC; 
                   (SEQ ID NO: 2) 
                 
                     
                     
                 
                     
                   HHHHHTHRLPRRRRRRHHHHHC; 
                   (SEQ ID NO: 3) 
                 
                     
                     
                 
                     
                   THRLPRRRRRRHHHHHHHHHHC; 
                   (SEQ ID NO: 4) 
                 
                     
                     
                 
                     
                   GGTHRLPRRRRRRHHHHHHHHHHC; 
                   (SEQ ID NO: 5) 
                 
                     
                     
                 
                     
                   THRLPRRRRRRGGHHHHHHHHHHC; 
                   (SEQ ID NO: 6) 
                 
                     
                     
                 
                     
                   THRLPRRRRRRHHHHHGGHHHHHC; 
                   (SEQ ID NO: 7) 
                 
                     
                     
                 
                     
                   THRLPRRRRRRHHHHHHHHHHC; 
                   (SEQ ID NO: 8) 
                 
                     
                   or 
                     
                 
                     
                     
                 
                     
                   CTHRLPRRRRRRHHHHHHHHHHC. 
                   (SEQ ID NO: 9) 
                 
             
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
                
               
            
           
         
       
     
     
         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 or preventing 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 . The method of  claim 6 , wherein the ocular disorder is associated with ocular angiogenesis, dry eye, ocular inflammatory conditions, ocular hypertension, or glaucoma. 
     
     
         8 . The method of  claim 7 , wherein the system is administered by intraocular injection, ocular topical application, subconjunctival injection, intravitreal injection, anterior or posterior juxtascleral injection, intravenous injection, oral administration, intramuscular injection, intraperitoneal injection, transdermal application, intranasal application, or transmucosal application. 
     
     
         9 . A method of delivering an interfering RNA molecule into a cell, comprising:
 (a) attaching an interfering RNA molecule to a YM3-10H peptide, 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.   
     
     
         10 . The method of  claim 9 , wherein the interfering RNA molecule is linked to the YM3-10H peptide via a covalent bond. 
     
     
         11 . The method of claim  13 , wherein the interfering RNA molecule is a siRNA, miRNA, or shRNA. 
     
     
         12 . The method of  claim 9 , wherein the YM3-1 OH peptide comprises: 
       
         
           
                 
                 
                 
               
                     
                   CHHHHHTHRLPRRRRRRHHHHHC; 
                   (SEQ ID NO: 2) 
                 
                     
                     
                 
                     
                   HHHHHTHRLPRRRRRRHHHHHC; 
                   (SEQ ID NO: 3) 
                 
                     
                     
                 
                     
                   THRLPRRRRRRHHHHHHHHHHC; 
                   (SEQ ID NO: 4) 
                 
                     
                     
                 
                     
                   GGTHRLPRRRRRRHHHHHHHHHHC; 
                   (SEQ ID NO: 5) 
                 
                     
                     
                 
                     
                   THRLPRRRRRRGGHHHHHHHHHHC; 
                   (SEQ ID NO: 6) 
                 
                     
                     
                 
                     
                   THRLPRRRRRRHHHHHGGHHHHHC; 
                   (SEQ ID NO: 7) 
                 
                     
                     
                 
                     
                   THRLPRRRRRRHHHHHHHHHHC; 
                   (SEQ ID NO: 8) 
                 
                     
                   or 
                     
                 
                     
                     
                 
                     
                   CTHRLPRRRRRRHHHHHHHHHHC. 
                   (SEQ ID NO: 9)