Long term expression of gene products

Abstract

A process for increasing the circulating levels of self gene products in a mammal for an extended period of time is provided. In accordance with that process, muscle cells of the mammal are transformed with an expression vector that contains a polynucleotide that encodes the gene product and which vector drives expression in the muscle.

I claim:  
     
         1 . A process for increasing the circulating levels of a self protein in the blood stream of an immunocompetent animal which comprises delivering a viral vector in vivo to muscle cells of said animal by intramuscular injection in an amount sufficient to obtain expression of and increase the circulating level of said self protein in the bloodstream of said animal for a period greater than about 30 days, wherein said self protein is a polypeptide hormone and undergoes secretion, diffusion or transport to the circulation upon expression in vivo.  
     
     
         2 . The process of  claim 1  wherein the animal is a primate.  
     
     
         3 . The process of  claim 2  wherein the primate is a human.  
     
     
         4 . The process of  claim 1  wherein the viral vector is a replication-defective adenoviral vector or a retroviral vector.  
     
     
         5 . The process of  claim 1  wherein the self protein is a cytokine, colony stimulating factor, nerve growth factor, insulin, glucagon, rennin, parathyroid hormone, growth hormone, growth factor or erythropoietin.  
     
     
         6 . The process of  claim 1  wherein the circulating level of the self protein is increased for a period of time greater than about 60 days.  
     
     
         7 . The process of  claim 1  wherein the circulating level of the self protein is increased for a period of time greater than about 90 days.  
     
     
         8 . The process of  claim 1  wherein the circulating level of the self protein is increased for a period of time greater than about 120 days.  
     
     
         9 . The process of  claim 1  wherein the circulating level of the self protein is increased for a period of time ranging from about 90 days to about 365 days.  
     
     
         10 . The process of  claim 1  wherein the muscle cells are cardiac muscle cells or skeletal muscle cells.  
     
     
         11 . The process of  claim 1 , wherein said immunocompetent animal is being treated with an immunosuppressant.  
     
     
         12 . A process for increasing the circulating levels of a self protein in the blood stream of an immunocompetent animal which comprises transforming muscle cells in vivo with a viral vector encoding a self protein, wherein the expression vector is delivered to said animal by intramuscular injection in an amount sufficient to obtain expression of and increase the circulating level of said self protein in the bloodstream of said animal for a period greater than about 30 days, wherein said self protein is a polypeptide hormone and undergoes secretion, diffusion or transport to the circulation upon expression in vivo.  
     
     
         13 . The process of  claim 12  wherein the animal is a primate.  
     
     
         14 . The process of  claim 13  wherein the primate is a human.  
     
     
         15 . The process of  claim 12  wherein the expression vector is a viral vector.  
     
     
         16 . The process of  claim 15  wherein the viral vector is a replication-defective adenoviral vector or a retroviral vector.  
     
     
         17 . The process of  claim 12  wherein the polypeptide is a cytokine, colony stimulating factor, nerve growth factor, insulin, glucagons, rennin, parathyroid hormone, growth hormone, growth factor or erythropoietin.  
     
     
         18 . The process of  claim 12  wherein the circulating level of the self protein is increased for a period of time greater than about 60 days.  
     
     
         19 . The process of  claim 12  wherein the circulating level of the self protein is increased for a period of time greater than about 90 days.  
     
     
         20 . The process of  claim 12  wherein the circulating level of the self protein is increased for a period of time greater than about 120 days.  
     
     
         21 . The process of  claim 12  wherein the circulating level of the self protein is increased for a period of time ranging from about 90 days to about 365 days.  
     
     
         22 . The process of  claim 12  wherein the muscle cells are cardiac muscle cells or skeletal muscle cells.  
     
     
         23 . The process of  claim 12 , wherein said immunocompetent animal is being treated with an immunosuppressant.  
     
     
         24 . A process for increasing the circulating levels of a self protein in the blood stream of an immunocompetent animal which comprises 
 transforming muscle cells of said animal ex vivo with an expression vector encoding a self protein; and    delivering said transformed muscle cells to said animal by intramuscular injection in an amount sufficient to obtain expression of and increase the circulating level of said self protein in the bloodstream of said animal for a period greater than about 30 days, wherein said self protein is a polypeptide hormone and undergoes secretion, diffusion or transport to the circulation upon expression in vivo.    
     
     
         25 . The process of  claim 24  wherein the animal is a primate.  
     
     
         26 . The process of  claim 25  wherein the primate is a human.  
     
     
         27 . The process of  claim 24  wherein the expression vector is a plasmid.  
     
     
         28 . The process of  claim 24  wherein the expression vector is a viral vector.  
     
     
         29 . The process of  claim 28  wherein the viral vector is a replication-defective adenoviral vector or a retroviral vector.  
     
     
         30 . The process of  claim 24  wherein the self protein is a cytokine, colony stimulating factor, nerve growth factor, insulin, glucagons, rennin, parathyroid hormone, growth hormone, growth factor or erythropoietin.  
     
     
         31 . The process of  claim 24  wherein the circulating level of the self protein is increased for a period of time greater than about 60 days.  
     
     
         32 . The process of  claim 24  wherein the circulating level of the self protein is increased for a period of time greater than about 90 days.  
     
     
         33 . The process of  claim 24  wherein the circulating level of the self protein is increased for a period of time greater than about 120 days.  
     
     
         34 . The process of  claim 24  wherein the circulating level of the self protein is increased for a period of time ranging from about 90 days to about 365 days.  
     
     
         35 . The process of  claim 24  wherein the muscle cells are cardiac muscle cells or skeletal muscle cells.  
     
     
         36 . The process of  claim 24 , wherein said immunocompetent animal is being treated with an immunosuppressant.