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 thymidine phosphorylase (TYMP) or a functional fragment thereof,
wherein the enucleated erythroid cell is made by a process comprising introducing an exogenous nucleic acid encoding the exogenous polypeptide into a nucleated erythroid cell precursor.
2 . The enucleated erythroid cell of claim 1 , which comprises at least 1,000 copies of the exogenous polypeptide.
3 . The enucleated erythroid cell of claim 1 , wherein the exogenous polypeptide is intracellular.
4 . The enucleated erythroid cell of claim 1 , which is not a hypotonically loaded cell.
5 . The enucleated erythroid cell of claim 1 , wherein the exogenous polypeptide consists essentially of TYMP.
6 . The enucleated erythroid cell of claim 1 , wherein the exogenous polypeptide consists of TYMP.
7 . The enucleated erythroid cell of claim 1 , wherein the exogenous nucleic acid comprises DNA.
8 . The enucleated erythroid cell of claim 1 , wherein the exogenous nucleic acid comprises RNA.
9 . The enucleated erythroid cell of claim 1 , which is a reticulocyte.
10 . The enucleated erythroid cell of claim 1 , which is an erythrocyte.
11 . The enucleated erythroid cell of claim 1 , which lacks A and B antigens.
12 . The enucleated erythroid cell of claim 1 , wherein the nucleated erythroid cell precursor is a CD34+ hematopoietic stem cell.
13 . The enucleated erythroid cell of claim 1 , which is a human cell.
14 . A pharmaceutical composition comprising a plurality of the enucleated erythroid cells of claim 1 .
15 . The pharmaceutical composition of claim 14 , wherein at least about 90% of enucleated erythroid cells in the pharmaceutical composition comprise the exogenous polypeptide.
16 . A pharmaceutical composition comprising a plurality of the enucleated erythroid cells of claim 1 , wherein at least 70% of the cells in the pharmaceutical composition are the enucleated erythroid cells.
17 . A nucleated erythroid cell precursor comprising an exogenous polypeptide comprising TYMP or a functional fragment thereof, wherein the nucleated erythroid cell precursor was made by a process comprising introducing an exogenous nucleic acid encoding the exogenous polypeptide into the nucleated erythroid cell precursor.
18 . The nucleated erythroid cell precursor of claim 17 , wherein the exogenous polypeptide is intracellular.
19 . The nucleated erythroid cell precursor of claim 17 , which has been cultured after the introduction of the exogenous nucleic acid.
20 . A method of treating mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising a plurality of enucleated erythroid cells comprising an exogenous polypeptide comprising TYMP or a functional fragment thereof, wherein each of the enucleated erythroid cells of said plurality was made by a process comprising introducing an exogenous nucleic acid encoding the exogenous polypeptide into a nucleated erythroid cell precursor.
21 . The method of claim 20 , wherein the exogenous polypeptide is intracellular.
22 . A method of treating MNGIE in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising a plurality of nucleated erythroid cell precursors comprising an exogenous polypeptide comprising TYMP or a functional fragment thereof, wherein each of the nucleated erythroid cell precursors of said plurality was made by a process comprising introducing an exogenous nucleic acid encoding the exogenous polypeptide into the nucleated erythroid cell precursor.
23 . The method of claim 22 , wherein the exogenous polypeptide is intracellular.
24 . The method of claim 22 , wherein the nucleated erythroid cell precursor has been cultured after the introduction of the exogenous nucleic acid.