Method for selectively transducing pathologic mammalian cells using a tumor suppressor gene

Abstract

A method for transducing a pathologic hyperproliferative mammalian cell is provided by this invention. This method requires contacting the cell with a suitable retroviral vector containing a nucleic acid encoding a gene product having a tumor suppressive function. Also provided by this invention is a method for treating a pathology in a subject caused by the absence of, or the presence of a pathologically mutated tumor suppressor gene.

We claim:  
     
         1 . A method for transducing a pathologic hyperproliferative mammalian cell comprising contacting the cell with a suitable retroviral vector containing a nucleic acid encoding a gene product having a tumor suppressive function, under suitable conditions such that the cell is transduced.  
     
     
         2 . The method of  claim 1 , wherein the gene product is expressed by a tumor suppressor gene.  
     
     
         3 . The method of  claim 2 , wherein the tumor suppressor gene is wild type p53 gene, retinoblastoma gene RB, Wilm's tumor gene WT1 or colon carcinoma gene DCC.  
     
     
         4 . The method of  claim 1 , wherein the suitable conditions are infecting the sample cells in the absence of selective medium.  
     
     
         5 . The method of  claim 1 , wherein the suitable retroviral vector lacks a selectable marker gene.  
     
     
         6 . The method of  claim 1 , wherein the suitable retroviral vector is replication-incompetent.  
     
     
         7 . The method of  claim 1 , wherein the pathological cells are prostate cells, psoriatic cells, thyroid cells, breast cells, colon cells, lung cells, sarcoma cells, leukemic cells or lymphoma cells.  
     
     
         8 . The method of  claim 1 , wherein the suitable time period is less than about ten hours.  
     
     
         9 . The method of  claim 8 , wherein the time period is about four hours.  
     
     
         10 . The method of  claim 1 , wherein suppressing the hyperproliferative phenotype is characterized by the transduced cell expressing a mature or benign phenotype.  
     
     
         11 . The method of  claim 1 , wherein suppressing the hyperproliferative phenotype is characterized by apoptosis or death of the transduced cell.  
     
     
         12 . The method of  claim 1 , wherein the contacting is effected ex vivo.  
     
     
         13 . The method of  claim 1 , wherein the contacting is effected in vivo.  
     
     
         14 . The method of  claim 1 , wherein the nucleic acid is RNA.  
     
     
         15 . The method of  claim 1 , wherein the mammal is a human.  
     
     
         16 . A method for treating a pathology in a subject caused by the absence of a tumor suppressor gene or the presence of a pathologically mutated tumor suppressor gene comprising administering to the subject an effective amount of a suitable retroviral vector containing a nucleic acid encoding a gene product having a tumor suppressive function, under suitable conditions.  
     
     
         17 . The method of  claim 16 , wherein the gene product is expressed by a tumor suppressor gene.  
     
     
         18 . The method of  claim 17 , wherein the tumor suppressor gene is wild type p53 gene, retinoblastoma gene RB, Wilm's tumor gene WT1 or colon carcinoma gene DCC.  
     
     
         19 . The method of  claim 16 , wherein the suitable retroviral vector is replication-incompetent.  
     
     
         20 . The method of  claim 16 , wherein the absence or presence of a pathologically mutated tumor suppressor gene causes a cell to hyperproliferate.  
     
     
         21 . The method of  claim 20 , wherein the hyperproliferative cell is a prostate cell, a psoriatic cell, a thyroid cell, a breast cell, a colon cell, a lung cell, a sarcoma cell, a leukemic cell or a lymphoma cell.  
     
     
         22 . The method of  claim 21 , wherein the treating of the hyperproliferative cell is characterized by apoptosis or death of the cell.  
     
     
         23 . The method of  claim 16 , wherein the contacting is effected in vivo.  
     
     
         24 . The method of  claim 16 , wherein the nucleic acid is RNA.