Purine nucleoside phosphorylase as enzymatic activator of nucleoside prodrugs

1. A process for inhibiting a mammalian cancerous cell or virally infected cell comprising:

providing a tail mutant purine nucleoside phosphorylase enzyme having a tail of between 10 and 50 additional amino acid residues and corresponding to a frame shift mutation within a terminal 150 nucleic acid residues associated with a nucleotide sequence associated with a wild type purine nucleoside phosphorylase in proximity to the cancerous mammalian cell or the virally infected cell; and

exposing the enzyme to a cleavable substrate to yield a cytotoxic purine analog.

2. The process of claim 1 wherein said substrate is 9-(β-D-arabinofuranosyl)-2-fluoroadenine (fludarabine), cladribine, an analog of cordycepin, an analog of 2′,3′-dideoxyadenosine, 5′-methyl(talo)-6-methyl-purine-riboside, 5′-methyl(talo)-2′-deoxy-6-methylpurine-riboside, 5′-methyl(allo)-6-methylpurine-riboside, 2-F-5′-deoxyadenosine, or 2-F-α-L-lyxo-adenine.

3. The process of claim 1 wherein providing the enzyme is by administering a viral vector coding a nucleotide sequence for said enzyme expressible in said cell.

4. The process of claim 1 wherein providing said enzyme is by direct injection, infection, lipofection, or biolistic administration of a nucleotide sequence for the enzyme expressible in the cell.

5. The process of claim 1 wherein providing said enzyme is by direct injection of the enzyme proximal to said cell.

6. The process of claim 1 wherein providing said enzyme is by administration to a subject or a subject cell modified to express said tail mutant purine nucleoside phosphorylase.

7. The process of claim 1 wherein providing is by intracellular delivery of an expressible nucleotide sequence encoding said enzyme.