Purine nucleoside phosphorylase gene therapy for human malignanc

Chemistry: molecular biology and microbiology – Spore forming or isolating process

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4351723, 4352521, 4353201, 424450, 514 2, 514 43, 514 44, 530350, 536 232, 536 237, 536 241, 935 70, 935 72, C12N 500, C12N 1500

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055523110

ABSTRACT:
The invention provides a method of killing replicating or non-replicating, transfected or transduced mammalian cells and bystander cells, comprising the following steps: (a) transfecting or transducing mammalian cells with a nucleic acid encoding a non-human purine nucleoside phosphorylase (PNP); and (b) contacting the transfected or transduced cells with an amount of a substrate for the purine nucleoside phosphorylase sufficient to produce a toxic purine base-analog thereby killing the transfected or transduced cells and bystander cells. In the present method of killing cells, the non-human purine nucleoside phosphorylase can be an E. coli purine nucleoside phosphorylase. The method of the invention described above can utilize a substrate that is a purine nucleoside analog. For instance, in the method provided in the Examples, the substrate is 9-(.beta.-D-2-deoxyerythropentofuranosyl)-6-methylpurine (MeP-dR).

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