Targeted therapeutics

Abstract

The present invention relates to compositions, methods and kits for delivery of active agents (X) to cells or tissues that express proteoglycans. More specifically, the present invention relates to conjugates comprising (HB-linker) n -X m -(linker-HB) o , where HB is a heparin binding protein, X is an active agent such as a therapeutic protein (including a functional fragment or variant thereof), or a therapeutic small molecule, linker is a linker entity and m is an integer of at least 1, and n+o is an integer of at least 1. Other aspects relate to use of a HB-X conjugate in methods to deliver active agents to cartilage for the treatment of cartilage related disease and disorders, the use of the HB-X conjugate in methods to deliver active agents to neuronal tissues (e.g., brain and spinal cord) for the treatment of neurological disorders, and the use of the HB-X conjugates in methods for the treatment of eye conditions and disorders and inflammatory conditions and disorders.

1 .- 35 . (canceled) 
     
     
         36 . A vector comprising a nucleic acid encoding at least one heparin binding peptide (HB) selected from KRKKKGKGLGKKRDPCLRKYK (SEQ ID NO: 1), KRKKKGKGLGKKRDPRLRKYK (SEQ ID NO:2), or KRKKKGKGLGKKRDPRLRKYK (SEQ ID NO:3). 
     
     
         37 . The vector of  claim 36 , further comprising at least one nucleic acid sequence encoding at least one active agent (X). 
     
     
         38 . The vector of  claim 36 , further comprising at least one nucleic acid sequence encoding at least one linker. 
     
     
         39 . The vector of  claim 37 , wherein the nucleic acid sequence encodes at least one HB-X n  or X n -HB n  fusion protein, wherein HB is a heparin binding peptide selected from KRKKKGKGLGKKRDPCLRKYK (SEQ ID NO: 1), KRKKKGKGLGKKRDPRLRKYK (SEQ ID NO:2), or KRKKKGKGLGKKRDPRLRKYK (SEQ ID NO:3); X is an active agent, and n is an integer of at least 1. 
     
     
         40 . The vector of  claim 38 , wherein the nucleic acid sequence encodes at least one (HB-linker) n -X n  or at least one X n -(HB-linker) n  fusion protein, or at least one (HB-linker) n -X m -(HB-linker) o  fusion protein, wherein HB is a heparin binding peptide selected from KRKKKGKGLGKKRDPCLRKYK (SEQ ID NO: 1), KRKKKGKGLGKKRDPRLRKYK (SEQ ID NO:2), or KRKKKGKGLGKKRDPRLRKYK (SEQ ID NO:3); X is an active agent, wherein m is an integer of at least 1, and n+o is an integer of at least 1. 
     
     
         41 . The vector of  claim 36 , wherein the linker comprises GGG. 
     
     
         42 . The vector of  claim 36 , wherein the nucleic acid sequence encoding the X or linker is 5′ to the nucleic acid encoding HB. 
     
     
         43 . The vector of  claim 36 , wherein the nucleic acid sequence encoding the X or linker is 3′ to the nucleic acid encoding HB. 
     
     
         44 . The vector of  claim 36 , wherein the nucleic acid sequence encoding the HB peptide is 5′ and 3′ of the nucleic acid encoding X or the linker. 
     
     
         45 . The vector of  claim 36 , wherein the vector is an expression vector. 
     
     
         46 .- 48 . (canceled)