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