Aventis Pharma S.a.

Michel Couder

Francis Blanche

Jo&euml;l Crouzet

B&eacute;atrice Cameron

David Gaillac

Thierry Guillemin

Nicolas Maestrali

Enzyme combinations useful for destroying cells, particularly proliferative cells, are disclosed. In particular, a combination of the following enzymes has been found to enhance the toxicity of nucleoside analogues to proliferating cells: an enzyme that phosphorylates the non-toxic nucleoside analogue to generate a monophosphate analogue, an enzyme that phosphorylates the monophosphate analogue to generate a diphosphate analogue and an enzyme that phosphorylates the diphosphate analogue to generate a toxic triphosphate analogue. Vectors enabling the intracellular expression and transfer of the enzyme combinations, as well as their therapeutic use, particularly in anti-cancer gene therapy, are also disclosed.

Enzyme combinations for destroying proliferative cells

The present invention relates to a nucleic acid sequence characterized in that it is derived from the wild nucleic acid sequence coding for a thymidine kinase, said nucleic acid sequence having at least one mutation in the region corresponding to the ATP binding site and conveniently a second mutation in the N-terminal region and/or C-terminal region. It also relates to variants of the wild thymidine kinase and their use in genic therapy.

Variants of thymidine kinase, nucleic acids encoding them, and methods of using them

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Sucy en Brie, France

Michel Couder