Mutated herpes simplex virus type 1 thymidine kinases and uses thereof
AssigneeBoard of Trustees of the University of Arkansas
InventorsCesar Compadre, Richard Drake, Trenton Hinds, Barry Hurlburt, Tammy Rechtin
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Abstract
The present invention provides new site-specific HSV-thymidine kinase mutants with improved nucleoside analog metabolizing activity due to low or no thymidine phosphorylation ability. Also provided is a method of killing target cells using such mutants combined with a prodrug.
Claims16
A mutant herpes simplex virus type 1 thymidine kinase protein, wherein said protein contains a site-specific mutation at amino acid position 125 of wild type herpes simplex virus type 1 thymidine kinase protein, wherein said amino acid at position 125 is glutamine.
A method of killing target cells in an individual in need of such treatment, comprising the steps of:
- (a) transfecting or transducing said target cells with a gene encoding a mutant herpes simplex virus type 1 thymidine kinase protein, wherein said protein contains a site-specific mutation at amino acid position 125 of wild type herpes simplex virus type 1 thymidine kinase protein, wherein said amino acid at position 125 is glutamine;
- and
- (b) contacting said transfected or transduced target cells with an effective amount of a prodrug, wherein said prodrug is a substrate for the mutant herpes simplex virus type 1 thymidine kinase to produce a toxic substance, wherein said toxic substance kills said transfected or transduced target cells.
Dependencies are inferred from the claim text.