Thymidylate kinase fusions and uses thereof
AssigneeUniversity Health Network
InventorsJEFFREY A. MEDIN, SEAN DEVINE
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Abstract
The application relates to a composition comprising: a stably integrating delivery vector; a modified mammalian thymidylate kinase (tmpk) wherein the modified mammalian tmpk increases phosphorylation of a prodrug relative to phosophorylation of the prodrug by wild-type human tmpk; and a detection cassette fused to tmpk. The application also relates to use of these compositions in methods of treatment of diseases such as graft versus host disease and cancer.
Claims21
1-82. (canceled)
A method of enhancing the capability of a mammalian cell in phosphorylating AZT comprising introducing into the cell a composition comprising:
- a stably integrating delivery vector;
- a modified mammalian thymidylate kinase (tmpk) polynucleotide that encodes a modified mammalian tmpk polypeptide that increases phosphorylation of AZT relative to phosphorylation of AZT by wild type mammalian tmpk polypeptide;
- and
- a detection cassette polynucleotide that encodes a detection cassette polypeptide that is cell surface expressed, wherein the detection cassette polynucleotide is fused to the modified mammalian tmpk polynucleotide and the detection cassette polypeptide is fused to the modified mammalian tmpk polypeptide.
A composition comprising:
- a stably integrating delivery vector;
- a modified mammalian thymidylate kinase (tmpk) polynucleotide that encodes a modified mammalian tmpk polypeptide that increases phosphorylation of AZT relative to phosphorylation of AZT by wild type mammalian tmpk polypeptide;
- and
- a detection cassette polynucleotide that encodes a detection cassette polypeptide that is cell surface expressed, wherein the detection cassette polynucleotide is fused to the modified mammalian tmpk polynucleotide and the detection cassette polypeptide is fused to the modified mammalian tmpk polypeptide.
A method of treating Fabry disease comprising administering an isolated cell, isolated virus or composition comprising:
- a stably integrating delivery vector;
- a modified mammalian thymidylate kinase (tmpk) polynucleotide that encodes a modified mammalian tmpk polypeptide that increases phosphorylation of AZT relative to phosphorylation of AZT by wild type mammalian tmpk polypeptide;
- a detection cassette polynucleotide that encodes a detection cassette polypeptide that is cell surface expressed, wherein the detection cassette polynucleotide is fused to the modified mammalian tmpk polynucleotide and the detection cassette polypeptide is fused to the modified mammalian tmpk polypeptide;
- and
- a therapeutic polynucleotide cassette selected from α-galactosidase A or codon optimized α-galactosidase A,
- to a subject in need thereof.
Dependencies are inferred from the claim text.