Peptides that target dorsal root ganglion neurons

Abstract

The present invention concerns methods and compositions that employ peptides that target dorsal root ganglion (DRG) neurons. In particular, the peptides are used to target therapeutic agents, such as proteins, liposomes, or viral particles comprising therapeutic polynucleotides, to one or more peripheral neuropathies or neuropathic pain, for example. In particular cases, the peripheral neuropathies or neuropathic pain is caused directly or indirectly by DRG neuronopathy.

What is claimed is: 
     
         1 . An isolated peptide of SEQ ID NO:1, SEQ ID NO:2, SEQ ID NO:3, or a modified peptide having one, two, or three conservative substitutions compared to SEQ ID NO:1, SEQ ID NO:2, or SEQ ID NO:3, respectively, or a combination thereof. 
     
     
         2 . The peptide of  claim 1 , comprised in a pharmaceutically acceptable excipient. 
     
     
         3 . The peptide of  claim 1 , linked to a protein or a liposome. 
     
     
         4 . The peptide of  claim 3 , wherein the protein is a therapeutic protein. 
     
     
         5 . The peptide of  claim 4 , wherein the therapeutic protein is NGF, EGF, FGF, BDNF, IGF1, CTNF, PDNF, VAD, DEVD, NGN1, NGN2, NGN3, RUNX3, or a signal peptide. 
     
     
         6 . The peptide of  claim 3 , wherein the protein is present on the surface of a helper-dependent adenoviral particle. 
     
     
         7 . The peptide of  claim 6 , wherein the particle is defined as further comprising a therapeutic polynucleotide. 
     
     
         8 . The peptide of  claim 7 , wherein the therapeutic polynucleotide is selected from the group consisting of NGF, EGF, FGF, BDNF, IGF1, CTNF, PDNF, VAD, DEVD, NGN1, NGN2, NGN3, RUNX3, IL-10, anti-TNFα, EPO, or prepro-β endorphin. 
     
     
         9 . A method of targeting a dorsal root ganglion (DRG) neuron in an individual, comprising the step of delivering to the individual an effective amount of one or more peptides of  claim 1 . 
     
     
         10 . A method of targeting a dorsal root ganglion (DRG) neuron in an individual, comprising the step of delivering to the individual an effective amount of one or more peptides of  claim 7 . 
     
     
         11 . The method of  claim 10 , wherein the individual has DRG neuronopathy. 
     
     
         12 . The method of  claim 11 , wherein the DRG neuronopathy results in a neuropathy selected from the group consisting of neuropathies associated with metabolic disease, hereditary disease, neoplasm, infectious disease, injury, or in autoimmune disease. 
     
     
         13 . The method of  claim 10 , wherein the individual has pain, hyperalgesia, hypoalgesia, or ataxia. 
     
     
         14 . The method of  claim 10 , wherein the helper-dependent adenoviral particle is delivered intrathecally. 
     
     
         15 . A method of treating a DRG neuronopathy in an individual, comprising the step of delivering to the individual an effective amount of a therapeutic agent linked to one or more peptides of  claim 1  or an effective amount of a liposome comprising a therapeutic agent, said liposome linked to one or more peptides of  claim 1 . 
     
     
         16 . A method of treating a DRG neuronopathy in an individual, comprising the step of delivering to the individual an effective amount of a therapeutic agent linked to one or more peptides of  claim 1  or an effective amount of a liposome comprising a therapeutic agent, said liposome linked to one or more peptides of  claim 7 . 
     
     
         17 . The method of  claim 16 , wherein the DRG neuronopathy results in a neuropathy selected from the group consisting of neuropathies associated with metabolic disease, hereditary disease, neoplasm, infectious disease, injury, or in autoimmune disease. 
     
     
         18 . The method of  claim 16 , wherein the individual has pain, hyperalgesia, hypoalgesia, or ataxia. 
     
     
         19 . The method of  claim 16 , wherein the helper-dependent adenoviral particle is delivered intrathecally. 
     
     
         20 . A polynucleotide encoding the peptide and protein of  claim 3 .