Synthetic membrane-receiver complexes

Abstract

Compositions comprising synthetic membrane-receiver complexes, methods of generating synthetic membrane-receiver complexes, and methods of treating or preventing diseases, disorders or conditions therewith.

What is claimed is: 
     
         1 . An enucleated erythroid cell comprising an exogenous polypeptide comprising oxalate oxidase or a functional fragment thereof. 
     
     
         2 . The enucleated erythroid cell of  claim 1 , which is not a hypotonically loaded cell. 
     
     
         3 . The enucleated erythroid cell of  claim 1 , wherein the enucleated erythroid cell is produced by a process comprising:
 providing a nucleated erythroid cell, or a precursor thereof, comprising an exogenous nucleic acid encoding the exogenous polypeptide; and   culturing the nucleated erythroid cell under conditions suitable for enucleation of the nucleated erythroid cell and for production of the exogenous polypeptide.   
     
     
         4 . The enucleated erythroid cell of  claim 3 , wherein the process of producing further comprises introducing the exogenous nucleic acid encoding the exogenous polypeptide into the nucleated erythroid cell, or the precursor thereof. 
     
     
         5 . The enucleated erythroid cell of  claim 3 , wherein the exogenous nucleic acid comprises a lentiviral vector comprising a nucleic acid sequence encoding the exogenous polypeptide. 
     
     
         6 . The enucleated erythroid cell of  claim 1 , wherein the enucleated erythroid cell exhibits substantially the same osmotic membrane fragility as a corresponding isolated, unmodified, uncultured erythroid cell. 
     
     
         7 . The enucleated erythroid cell of  claim 1 , which comprises at least 1,000 copies of the exogenous polypeptide. 
     
     
         8 . The enucleated erythroid cell of  claim 1 , which comprises at least 10,000 copies of the exogenous polypeptide. 
     
     
         9 . The enucleated erythroid cell of  claim 1 , which comprises at least 50,000 copies of the exogenous polypeptide. 
     
     
         10 . The enucleated erythroid cell of  claim 1 , which comprises at least 100,000 copies of the exogenous polypeptide. 
     
     
         11 . The enucleated erythroid cell of  claim 1 , wherein the oxalate oxidase is on the surface of the enucleated erythroid cell. 
     
     
         12 . The enucleated erythroid cell of  claim 1 , wherein the oxalate oxidase is intracellular. 
     
     
         13 . The enucleated erythroid cell of  claim 12 , which further comprises a second exogenous polypeptide comprising a transporter for a substrate of the oxalate oxidase. 
     
     
         14 . The enucleated erythroid cell of  claim 1 , which is a reticulocyte or mature erythrocyte. 
     
     
         15 . The enucleated erythroid cell of  claim 1 , which exhibits an increase in oxalate oxidase activity of at least 2-fold relative to that of an enucleated erythroid cell that does not comprise the exogenous polypeptide. 
     
     
         16 . A nucleated erythroid cell precursor cell comprising an exogenous nucleic acid that encodes an exogenous polypeptide comprising oxalate oxidase or a functional fragment thereof. 
     
     
         17 . A pharmaceutical composition comprising the enucleated erythroid cell of  claim 1 , further comprising a pharmaceutically acceptable carrier. 
     
     
         18 . A pharmaceutical composition comprising a population of erythroid cells comprising an exogenous polypeptide comprising oxalate oxidase or a functional fragment thereof, wherein the population of erythroid cells is greater than 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, 99.5% or 99.9% enucleated. 
     
     
         19 . A method of treating primary hyperoxaluria, the method comprising administering intravenously to a subject in need thereof the pharmaceutical composition of  claim 17 , thereby treating said primary hyperoxaluria. 
     
     
         20 . A method of reducing oxalate levels in a subject, the method comprising administering to the subject the pharmaceutical composition of  claim 17 , thereby reducing oxalate levels in the subject.