HIGHLY BRANCHED HK PEPTIDES AS EFFECTIVE CARRIERS OF siRNA

Abstract

The present invention is directed to methods of transfecting cells with siRNA, by contacting a transfection complex with one or more cells, where the transfection complex includes a transport polymer and siRNA. The transport polymer may include for example, H 3 K8b and/or structurally similar compounds. The invention is also directed to such transfection complexes, and to compositions that include such transfection complexes. The invention is further directed to methods of treating patients using the transfection complexes of the present invention.

1 - 15 . (canceled) 
     
     
         16 . A method of making a transfection complex comprising
 mixing siRNA with a transport polymer comprising histidine and lysine;   wherein the transport polymer comprises 8 terminal branches.   
     
     
         17 . The method of  claim 16 , wherein a ratio of the transport polymer to the siRNA is about 0.5:1 (wt/wt) to about 24:1 (wt/wt). 
     
     
         18 . The method of  claim 16 , wherein the polymer comprises at least one terminal branch having a sequence of -HHHKHHHKHHHKHHHKHHH- (SEQ ID NO: 11) or subsegment thereof. 
     
     
         19 . The method of  claim 16 , wherein the polymer comprises one or more polymers selected from the group consisting of H 3 K8b (comprising SEQ ID NO: 14), H 3 K8b (+RGD) (comprising SEQ ID NO: 14 and SEQ ID NO: 15), (−HHHK)H 3 K8b (comprising SEQ ID NO: 16 and SEQ ID NO: 17), and (−HHHK)H 3 K8b(+RGD) (comprising SEQ ID NO: 16 and SEQ ID NO: 17). 
     
     
         20 - 30 . (canceled) 
     
     
         31 . A method of making a transfection complex comprising
 mixing siRNA with a transport polymer;   wherein said transport polymer comprises one or more polymers selected from the group consisting of H 3 K8b (comprising SEQ ID NO: 14), H 3 K8b (+RGD) (comprising SEQ ID NO: 14 and SEQ ID NO: 15), (−HHHK)H 3 K8b (comprising SEQ ID NO: 16 and SEQ ID NO: 17), and (−HHHK)H 3 K8b(+RGD) (comprising SEQ ID NO: 16 and SEQ ID NO: 17).   
     
     
         32 . The method of  claim 31 , wherein the transport polymer comprises at least one stabilizing agent. 
     
     
         33 . The method of  claim 32 , wherein the stabilizing agent comprises PEG. 
     
     
         34 . The method of  claim 32 , wherein the stabilizing agent comprises a hydrophilic polymer. 
     
     
         35 . The method of  claim 31 , wherein the transport polymer comprises a targeting ligand. 
     
     
         36 . The method of  claim 31 , wherein said transport polymer comprises H 3 K8b (comprising SEQ ID NO: 14). 
     
     
         37 . The method of  claim 31 , wherein said transport polymer comprises H 3 K8b (+RGD) (comprising SEQ ID NO: 14 and SEQ ID NO: 15). 
     
     
         38 . The method of  claim 31 , wherein said transport polymer comprises (−HHHK)H 3 K8b (comprising SEQ ID NO: 16 and SEQ ID NO: 17). 
     
     
         39 . The method of  claim 31 , wherein said transport polymer comprises (−HHHK)H 3 K8b(+RGD) (comprising SEQ ID NO: 16 and SEQ ID NO: 17).