The Uab Research Foundation (the University of Alabama at Birmingham)

Other

Southern Research Institute

Southern Research Inst.

Leonard L Bennett, Jr

Eric J Sorscher

William B Parker

Vijayakrishna K Gadi

William Waud

The present invention provides a procaryotic host cell stably transformed or transfected by a vector including a DNA sequence encoding for purine nucleoside phosphorylase or hydrolase. The transformed or transfected procaryotic host cell can be used in combination with a purine substrate to treat tumor cells and/or virally infected cells.

Recombinant bacterial cells for delivery of PNP to tumor cells

The present invention provides a method of killing replicating or non-replicating, transfected or transduced mammalian cells and bystander cells, comprising: (a) transfecting or transducing mammalian cells with a nucleic acid encoding a non-human purine cleavage enzyme; and (b) contacting the transfected or transduced cells with an effective amount of a substrate for the purine cleavage enzyme, wherein the substrate is non-toxic to mammalian cells and is cleaved by the enzyme to yield a purine toxic to the targeted mammalian cells and bystander cells, to kill the mammalian cells expressing the enzyme and the bystander cells. Further provided is a vector comprising a DNA sequence coding for a non-human purine nucleoside phosphorylase protein and the vector is capable of replication and/or expression in a host which comprises, in operable linkage: a) optionally, an origin of replication; b) a promoter; and c) a DNA sequence coding for said protein.

Purine nucleoside phosphorylase gene therapy for human malignancy

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).

Growing community of inventors

Birmingham, AL, United States of America

Leonard L Bennett, Jr