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Thymidine kinase mutants
| Details |
Inventors: Loeb, Lawrence A.; Black, Margaret E.;
Assignee: University of Washington (Seattle, WA)
Primary Examiner: Elliott; George C.
Assistant Examiner: Brusca; John S.
Attorney, Agent or Firm: Seed and Berry LLP
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. |
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DETAILED DESCRIPTION Briefly stated, the present invention provides compositions and methods which utilize Herpesviridae thymidine kinase mutants.
Within one aspect of the present invention, isolated nucleic acid molecules which encode Herpesviridae thymidine kinase enzymes comprising one or more mutations are provided, 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, the mutation is an amino acid substitution within a DRH nucleoside binding site which increases a biological activity of said thymidine kinase, as compared to unmutated thymidine kinase.
Within yet another aspect, isolated nucleic acid molecules are provided encoding a Herpesviridae thymidine kinase enzyme comprising one or more mutations, at least one of the mutations being an amino acid substitution downstream from a DRH nucleoside binding site (e.
g.
, 4, 5 or 6 nucleotides downstream) which increases a biological activity of the thymidine kinase, as compared to unmutated thymidine kinase.
Representative examples of suitable flerpesviridae thymidine kinase enzymes include Herpes Simplex Virus Type 1 thymidine kinase, Herpes Simplex Virus Type 2 thymidine kinase, Varicella Zoster Virus thymidine kinase, and marmoset herpesvirus, feline herpesvirus type 1, pseudorabies virus, equine herpesvirus type 1, bovine herpesvirus type 1, turkey herpesvirus, Marek's disease virus, herpesvirus saimiri and Epstein-Barr virus thymidine kinases.
Within other embodiments, the thymidine kinase may be a primate herpesvirus thymidine kinase, or a non-primate herpesvirus thymidine kinase, such as an avian herpesvirus thymidine kinase.
A wide variety of mutations are contemplated within the context of the present invention.
For example, within one embodiment mutations which encode one or more amino acid substitutions from 1 to 7 amino acids upstream from the DRH nucleoside binding site are described
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