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:
 (i) a first exogenous polypeptide comprising uricase, or a functional fragment thereof, and   (ii) a second exogenous polypeptide comprising a transporter for a substrate of the uricase.   
     
     
         2 . The enucleated erythroid cell of  claim 1 , which comprises at least 1,000 copies of the first exogenous polypeptide. 
     
     
         3 . The enucleated erythroid cell of  claim 1 , which comprises at least 10,000 copies of the first exogenous polypeptide. 
     
     
         4 . The enucleated erythroid cell of  claim 1 , which comprises at least 50,000 copies of the first exogenous polypeptide. 
     
     
         5 . The enucleated erythroid cell of  claim 1 , which comprises at least 100,000 copies of the first exogenous polypeptide. 
     
     
         6 . The enucleated erythroid cell of  claim 1 , wherein the uricase is intracellular. 
     
     
         7 . The enucleated erythroid cell of  claim 1 , wherein the uricase is on the surface of the enucleated erythroid cell. 
     
     
         8 . The enucleated erythroid cell of  claim 1 , which is a reticulocyte or mature erythrocyte. 
     
     
         9 . 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, or wherein the enucleated erythroid cell is not a hypotonically loaded cell. 
     
     
         10 . The enucleated erythroid cell of  claim 1 , which was produced by a process comprising:
 providing a nucleated erythroid cell, or a precursor thereof, comprising (i) a first exogenous nucleic acid encoding the first exogenous polypeptide and (ii) a second nucleic acid encoding the second exogenous polypeptide; and   culturing the nucleated erythroid cell, or the precursor thereof, under conditions suitable for enucleation of the nucleated erythroid cell and for production of the first exogenous polypeptide and the second exogenous polypeptide.   
     
     
         11 . The enucleated erythroid cell of  claim 10 , wherein the process of producing further comprises introducing the first and second exogenous nucleic acids into the nucleated erythroid cell, or the precursor thereof. 
     
     
         12 . The enucleated erythroid cell of  claim 10 , wherein the first and second exogenous nucleic acids are situated in a lentiviral vector. 
     
     
         13 . The enucleated erythroid cell of  claim 1 , which exhibits an increase in uricase activity of at least 2-fold relative to that of an enucleated erythroid cell that does not comprise the first exogenous polypeptide. 
     
     
         14 . The enucleated erythroid cell of  claim 1 , wherein the substrate is uric acid. 
     
     
         15 . A pharmaceutical composition comprising a plurality of the enucleated erythroid cells of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         16 . The pharmaceutical composition of  claim 15 , which comprises a population of erythroid cells that is greater than 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99%, 99.5% or 99.9% enucleated. 
     
     
         17 . A method of reducing uric acid levels in a subject, comprising administering to the subject the pharmaceutical composition of  claim 15 , thereby reducing uric acid levels in the subject. 
     
     
         18 . A method of treating gout, the method comprising administering intravenously to a subject in need thereof the pharmaceutical composition of  claim 15 , thereby treating said gout. 
     
     
         19 . The method of  claim 18 , wherein the gout is gout with hyperuricemia. 
     
     
         20 . A method of treating Lesch-Nyhan syndrome, the method comprising administering intravenously to a subject in need thereof the pharmaceutical composition of  claim 15 , thereby treating said Lesch-Nyhan syndrome.