Delivery of therapeutic gene products by intestinal cell expression

Abstract

Intestinal epithelial cells of a mammalian subject are genetically altered to operatively incorporate a gene which expresses a protein which has a desired therapeutic effect. Intestinal cell transformation is accomplished by administration of a formulation containing DNA and is preferably administered orally. Oral or other intragastrointestinal routes of administration provide a simple method of administration. The expressed protein is secreted directly into the gastrointestinal tract and/or bloodstream to obtain therapeutic blood levels of the protein, thereby treating the patient in need of the protein. The delivery system of the invention provides short or long term delivery of therapeutic gene products.

1 . A method of delivering a secreted protein into the bloodstream of a mammalian subject, the method comprising: 
 introducing into the gastrointestinal tract of a mammalian subject a construct comprising (a) a nucleic acid molecule comprising a coding sequence encoding a secreted protein and (b) a promoter sequence operably linked to the coding sequence, wherein said construct is not packaged in a viral particle, said introducing resulting in introduction of the construct into an intestinal epithelial cell, production of the encoded protein in the intestinal epithelial cell and secretion of the protein from the cell and into the bloodstream of the subject.    
     
     
         2 . The method of  claim 1 , wherein the construct is administered by suppository administration.  
     
     
         3 . The method of  claim 1 , wherein the protein is altered relative to a wild-type protein.  
     
     
         4 . The method of  claim 1 , wherein the construct is formulated as a liquid, a solid, a pill, a capsule, a tablet, a solution, a gel, a syrup, a slurry or a suspension.  
     
     
         5 . The method of  claim 1 , wherein the construct is formulated to facilitate swallowing.