Nucleic acids encoding fusion proteins having thymidine kinase and guanylate kinase activities
AssigneeDarwin Molecular Corporation
InventorMargaret E Black
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AssigneeDarwin Molecular Corporation
InventorMargaret E Black
Estimating the term…
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 located toward the N-terminus from a DRH nucleoside binding site which increases a biological activity of the thymidine kinase, as compared to unmutated thymidine kinase. Such mutations include amino acid substitutions within a Q substrate binding domain which increases a biological activity of the thymidine kinase, as compared to unmutated thymidine kinase. Within a further aspect, fusion proteins are provided which have both guanylate kinase and thymidine kinase biological properties. Also provided are vectors suitable for expressing such DNA molecules, as well as methods for utilizing such vectors.
An isolated nucleic acid molecule encoding a fusion protein comprising a guanylate kinase moiety comprising SEQ ID NO. 49 and a thymidine kinase moiety, wherein said fusion protein possesses a biological activity of guanylate kinase and a biological activity of thymidine kinase, wherein said thymidine kinase moiety comprises either a Herpesviridae thymidine kinase of SEQ ID. NO. 134 or a mutant Herpesviridae thymidine kinase of SEQ ID. NO. 134 with an amino acid substitution at one or more of positions 160, 161 or 168 that possesses an increased biological activity when compared to the Herpesviridae thymidine kinase of SEQ ID. NO. 134.
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