Thymidine kinase mutants

C - Chemistry – Metallurgy – 12 – N

Patent

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Details

C12N 15/54 (2006.01) A61K 31/70 (2006.01) C12N 9/12 (2006.01) A61K 38/00 (2006.01) A61K 48/00 (2006.01)

Patent

CA 2189543

The present invention provides isolated nucleic acid molecules encoding a Herpesviridae thymidine kinase enzyme comprising one or more mutations, at least one of the mutations encoding an amino acid substitution upstream from a DRH nucleoside binding site which increases a biological activity of the thymidine kinase, as compared to unmutated thymidine kinase. Within another aspect, one of the mutations is an amino acid substitution within a DRH nucleoside binding site which increases a biological activity of the thymidine kinase, as compared to unmutated thymidine kinase. Also provided are vectors suitable for expressing such DNA molecules, as well as methods for utilizing such vectors.

L'invention porte sur des molécules d'acide nucléique isolées codant pour l'enzyme thymidine kinase du Herpesviridae présentant une ou plusieurs mutations, dont une au moins code pour une substitution d'acide aminé en amont du site de fixation du nucléoside DRH, laquelle accroît l'activité biologique de la thymidine kinase par rapport à celle qu'elle présente sans mutation. Dans une variante, l'une des mutations consiste en une substitution d'acide aminé à l'intérieur du site de fixation du nucléoside DRH, laquelle accroît l'activité biologique de la thymidine kinase par rapport à celle qu'elle présente sans mutation. L'invention porte également sur des vecteurs susceptibles d'exprimer lesdites molécules d'ADN et sur leurs modes d'utilisation.

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