Compositions and methods for performing reverse gene therapy

Abstract

The invention relates to compositions and methods for reverse gene therapy, wherein a gene therapy vector encoding a gene product (e.g. a protein) which is usually only expressed in cells of an abnormal tissue is delivered to a cell of an animal afflicted with a disease or disorder to alleviate the disease or disorder. In one embodiment, a plasmid vector encoding HERG (A561V) protein is delivered to a cell of an animal afflicted with re-entrant atrial flutter-mediated cardiac arrhythmia.

1 - 20 . (canceled) 
     
     
         21 . A method of alleviating a disease or disorder in an affected tissue, said method comprising locally delivering to the tissue, a reverse gene therapy vector, said vector contained within a cell, said vector comprising a promoter operably linked with a nucleic acid encoding a therapeutic gene product which is usually only expressed in cells of an abnormal tissue that is not afflicted with the disease or disorder, whereby delivery of said cell containing said reverse gene therapy vector to the affected tissue alleviates the disease or disorder. 
     
     
         22 . The method of  claim 21 , wherein said therapeutic gene product is a protein. 
     
     
         23 . The method of  claim 22 , wherein said protein is Q9E-hMirp1. 
     
     
         24 . The method of  claim 22 , wherein said cell is a mesenchymal stem cell. 
     
     
         25 . The method of  claim 24 , wherein said stem cell is an embryonic pluripotent stem cell and said protein is selected from the group consisting of an apoptosis-inducing protein, transcription factor E2F1, tenascin C, bone morphogenic protein, a protein involved in synthesis of a glycosaminoglycan, a dominant negative mutant receptor protein, transcription factor NF-ATc, and a degradation resistant collagen protein. 
     
     
         26 . The method of  claim 23 , wherein activity of said Q9E-hMirp1 is modulated via administration of clarithromycin. 
     
     
         27 . The method of  claim 24 , wherein activity of said Q9E-hMirp1 is modulated via administration of clarithromycin. 
     
     
         28 . The method of  claim 21 , wherein said reverse gene therapy vector is selected from the group consisting of naked DNA, a plasmid, a condensed nucleic acid, and a virus vector comprising a nucleic acid. 
     
     
         29 . The method of  claim 24 , wherein said stem cell is selected from the group consisting of a hematopoietic stem cells, pluripotent embryonic stem cells, skin stem cells and mesenchymal stem cells. 
     
     
         30 . The method of  claim 28 , wherein said condensed nucleic acid comprises a DNA molecule and a polycationic condensing agent. 
     
     
         31 . The method of  claim 30 , wherein said polycationic condensing agent is selected from the group consisting of poly-L-lysine and Ca 2+  ions. 
     
     
         32 . The method of  claim 21 , wherein said reverse gene therapy vector is delivered to the afflicted tissue in a form selected from a particle comprising said vector, a microparticle comprising said particle, a nanoparticle comprising said vector, an implantable device having a surface coated with a matrix comprising said vector, and a bulk material comprising said vector. 
     
     
         33 . The method of  claim 32 , wherein said implantable device comprises an electrode located in close proximity to a myocardial tissue of the animal. 
     
     
         34 . The method of  claim 33 , wherein the myocardial tissue is right atrial myocardium. 
     
     
         35 . A reverse gene therapy vector as shown in  FIG. 10 .