Erythroid cells comprising phenylalanine ammonia lyase
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 phenylalanine ammonia lyase (PAL) 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 , wherein the enucleated erythroid cell further comprises a second exogenous polypeptide which is surface-localized and comprises a phenylalanine transporter.
3. The enucleated erythroid cell of claim 1 , which comprises at least 1,000 copies of the exogenous polypeptide.
4. The enucleated erythroid cell of claim 1 , wherein the exogenous polypeptide is intracellular.
5. The enucleated erythroid cell of claim 1 , wherein the exogenous polypeptide consists essentially of PAL.
6. The enucleated erythroid cell of claim 1 , wherein the exogenous polypeptide consists of PAL.
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 of claim 1 .
17. A nucleated erythroid cell precursor comprising an exogenous polypeptide comprising PAL 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. The nucleated erythroid cell precursor of claim 17 , which further comprises a second exogenous polypeptide which is surface-localized and comprises a phenylalanine transporter.
21. A method of reducing phenylalanine concentration in the blood of a subject, comprising administering to the subject a pharmaceutical composition comprising a plurality of enucleated erythroid cells comprising an exogenous polypeptide comprising PAL, 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.
22. The method of claim 21 , wherein the exogenous polypeptide is intracellular.
23. The method of claim 21 , wherein the enucleated erythroid cells further comprise a second exogenous polypeptide which is surface-localized and comprises a phenylalanine transporter.
24. A method of reducing phenylalanine concentration in the blood of a subject, comprising administering to the subject a pharmaceutical composition comprising a plurality of nucleated erythroid cell precursors comprising an exogenous polypeptide comprising PAL, 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.
25. The method of claim 24 , wherein the exogenous polypeptide is intracellular.
26. The method of claim 24 , wherein the nucleated erythroid cell precursor has been cultured after the introduction of the exogenous nucleic acid.
27. The method of claim 24 , wherein the nucleated erythroid cell precursors further comprise a second exogenous polypeptide which is surface-localized and comprises a phenylalanine transporter.