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 . A non-hypotonically loaded enucleated erythroid cell comprising an exogenous polypeptide comprising cystathionine beta synthase (CBS) or a functional fragment thereof. 
     
     
         2 . The non-hypotonically loaded enucleated erythroid cell of  claim 1 , further comprising a second exogenous polypeptide comprising a transporter for a substrate of the CBS. 
     
     
         3 . The non-hypotonically loaded enucleated erythroid cell of  claim 1 , which comprises at least 1,000 copies of the exogenous polypeptide. 
     
     
         4 . The non-hypotonically loaded enucleated erythroid cell of  claim 1 , which comprises at least 10,000 copies of the exogenous polypeptide. 
     
     
         5 . The non-hypotonically loaded enucleated erythroid cell of  claim 1 , which comprises at least 50,000 copies of the exogenous polypeptide. 
     
     
         6 . The non-hypotonically loaded enucleated erythroid cell of  claim 1 , which comprises at least 100,000 copies of the exogenous polypeptide. 
     
     
         7 . The non-hypotonically loaded enucleated erythroid cell of  claim 1 , wherein the CBS is intracellular. 
     
     
         8 . The non-hypotonically loaded enucleated erythroid cell of  claim 1 , wherein the CBS is on the surface of the enucleated erythroid cell. 
     
     
         9 . The non-hypotonically loaded enucleated erythroid cell of  claim 1 , which is a reticulocyte or mature erythrocyte. 
     
     
         10 . The non-hypotonically loaded enucleated erythroid cell of  claim 1 , which was 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, or the precursor thereof, under conditions suitable for enucleation of the nucleated erythroid cell and for production of the exogenous polypeptide.   
     
     
         11 . The non-hypotonically loaded enucleated erythroid cell of  claim 10 , wherein the process of producing further comprises introducing the exogenous nucleic acid into the nucleated erythroid cell, or the precursor thereof. 
     
     
         12 . The non-hypotonically loaded enucleated erythroid cell of  claim 10 , wherein the exogenous nucleic acid is situated in a lentiviral vector. 
     
     
         13 . The non-hypotonically loaded enucleated erythroid cell of  claim 1 , which exhibits an increase in CBS activity of at least 2-fold relative to that of an enucleated erythroid cell that does not comprise the exogenous polypeptide. 
     
     
         14 . The non-hypotonically loaded enucleated erythroid cell of  claim 1 , wherein the substrate is homocysteine. 
     
     
         15 . A pharmaceutical composition comprising a plurality of the non-hypotonically loaded 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 homocysteine levels in a subject, comprising administering to the subject the pharmaceutical composition of  claim 15 , thereby reducing homocysteine levels in the subject. 
     
     
         18 . A method of treating homocystinuria, the method comprising administering intravenously to a subject in need thereof the pharmaceutical composition of  claim 15 , thereby treating said homocystinuria.