Gene therapy by secretory gland expression

Abstract

Secretory gland cells, particularly pancreatic and salivary gland cells, are genetically altered to operatively incorporate a gene which expresses a protein which has a desired therapeutic effect on a mammalian subject. The expressed protein is secreted directly into the gastrointestinal tract and/or blood stream to obtain therapeutic blood levels of the protein thereby treating the patient in need of the protein. The transformed secretory gland cells provide long term therapeutic cures for diseases associated with a deficiency in a particular protein or which are amenable to treatment by overexpression of a protein.

What is claimed is:  
     
         1 . A method of treatment, comprising: 
 genetically transforming cells of a secretory gland of a mammalian patient with a construct comprising a DNA of interest which expresses a protein that the patient is in need of and a eukaryotic promoting sequence operably linked to the DNA of interest; and    allowing the genetically transformed cells to express the protein in a therapeutically effective amount thereby treating the patient.    
     
     
         2 . The method of  claim 1 , wherein the secretory gland is selected from the group consisting of the salivary gland and the pancreas.  
     
     
         3 . The method of  claim 2 , wherein the salivary gland is a parotid gland.  
     
     
         4 . The method of  claim 1 , wherein the protein is secreted into the blood stream and the protein is selected from the group consisting of: insulin, growth hormone, clotting factor VIII, and erythropoietin.  
     
     
         5 . The method of  claim 1 , wherein the mammalian patient is a human the protein is a human protein and the secretory gland is a pancreas.  
     
     
         6 . The method of  claim 1 , wherein the protein is human growth hormone and the secretory gland is a pancreas.  
     
     
         7 . The method of  claim 6 , where the cells of the pancreas are transformed in vivo by injecting a solution comprising vectors which vectors comprise DNA expressing human growth hormone.  
     
     
         8 . The method of  claim 6 , wherein the mammalian patient is a human and the protein is human clotting factor VIII.  
     
     
         9 . The method of  claim 6 , wherein the mammalian patient is a human and the protein is human intrinsic factor.  
     
     
         10 . The method of  claim 6 , wherein the mammalian patient is a human and the protein is human erythropoietin.  
     
     
         11 . The method of  claim 1 , wherein the promoter sequence is an amylase promoter.  
     
     
         12 . The method of  claim 11 , wherein the secretory gland is the pancreas and the amylase promoter is a pancreatic α-amylase promoter.  
     
     
         13 . The method of  claim 11 , wherein the secretory gland is a salivary gland and the amylase promoter is a salivary α-amylase promoter.  
     
     
         14 . The method of  claim 1 , wherein the DNA of interest and promoter are incorporated into a viral vector.  
     
     
         15 . The method of  claim 5 , wherein the protein is secreted into the gastrointestinal tract.  
     
     
         16 . The method of  claim 6 , wherein the protein is secreted into the patient's saliva.  
     
     
         17 . A genetically transformed secretory gland cell, comprising: 
 a DNA of interest which expresses a therapeutically effective protein which DNA is artificially and operatively inserted in the genome of the cell;    a promoter operatively linked to the DNA.    
     
     
         18 . The cell of  claim 17 , wherein the promoter is a amylase promoter.  
     
     
         19 . The cell of  claim 17 , wherein the cell is a human salivary gland cell and the promoter is a human salivary amylase promoter.  
     
     
         20 . The cell of  claim 17 , wherein the cell is a human pancreatic cell and the promoter is a human pancreatic α-amylase promoter.