Methods and compositions for treating neuropathic pain

Abstract

Compositions and methods for the treatment of neuropathic pain are provided. Compositions of the invention may comprise proteins with a zinc-finger domain fused to a regulatory domain that is capable of either activating or repressing the expression of a target gene involved in neuropathic pain. Alternatively, compositions of the invention may comprise a nucleic acid sequence encoding a protein of the invention, which nucleic acid sequence may optionally be provided as a plasmid or within a virus or other vector for delivery to a target cell or tissue. Methods of treating neuropathic pain involving treatment of subject with the compositions of the invention are also provided. Exemplary target genes for the treatment of neuropathic pain include VR1, NaV 1.8 , and TrkA.

1 - 9 . (canceled) 
     
     
         10 . A nucleic acid encoding a protein comprising a zinc finger protein (ZFP) that is capable of regulating the expression of a TRK-A gene. 
     
     
         11 . The nucleic acid of  claim 10 , wherein the protein comprises a ZFP fused to a repression domain. 
     
     
         12 . The nucleic acid of  claim 10 , wherein the zinc finger protein binds to a target site having a nucleotide sequence selected from AAGGCGgGGCCGGGCGGGG, GAGGGGcAAGGCGgGGCCGG, CGCACCCTGCCCCGATGC, GAGTAGGAAGCGgGTGGAG, CTGCCCCCACGGCTCCTC, or AGCCGCCGCTGCCCTAGC. 
     
     
         13 . The nucleic acid of  claim 10 , wherein the nucleic acid is part of an expression vector. 
     
     
         14 . The nucleic acid of  claim 13 , wherein the expression vector is a plasmid. 
     
     
         15 . The nucleic acid of  claim 13 , wherein the expression vector is a viral vector. 
     
     
         16 . The nucleic acid of  claim 10 , wherein the zinc finger protein is engineered to bind a chosen target site in the TRK-A gene. 
     
     
         17 . A purified protein comprising a zinc finger protein (ZFP) that is capable of regulating the expression of a TRK-A gene. 
     
     
         18 . The protein of  claim 17 , wherein the protein comprises a ZFP fused to a repression domain. 
     
     
         19 . The protein of  claim 17 , wherein the zinc finger protein binds to a target site having a nucleotide sequence selected from AAGGCGgGGCCGGGCGGGG, GAGGGGcAAGGCGgGGCCGG, CGCACCCTGCCCCGATGC, GAGTAGGAAGCGgGTGGAG, CTGCCCCCACGGCTCCTC, or AGCCGCCGCTGCCCTAGC. 
     
     
         20 . A method of treating neuropathic pain comprising: administering to a subject having neuropathic pain a protein comprising a zinc finger protein (ZFP) that is capable of regulating the expression of a TRK-A gene or a nucleic acid encoding the protein. 
     
     
         21 . The method of  claim 20 , wherein the protein comprises a ZFP fused to a repression domain. 
     
     
         22 . The method of  claim 20 , wherein the protein comprising the zinc finger protein or nucleic acid encoding the protein is administered as a pharmaceutical composition further comprising a pharmaceutically acceptable carrier. 
     
     
         23 . The method of  claim 11 , wherein the zinc finger protein binds to a target site having a nucleotide sequence selected from AAGGCGgGGCCGGGCGGGG, GAGGGGcAAGGCGgGGCCGG, CGCACCCTGCCCCGATGC, GAGTAGGAAGCGgGTGGAG, CTGCCCCCACGGCTCCTC, or AGCCGCCGCTGCCCTAGC. 
     
     
         24 . The nucleic acid of  claim 11 , wherein the nucleic acid is administered as part of an expression vector. 
     
     
         25 . The method of  claim 15 , wherein the expression vector is a plasmid. 
     
     
         26 . The method of  claim 15 , wherein the expression vector is a viral vector.