Construction and Use of Mutant Herpes Thymidine Kinase Genes in Cancer Therapy
Introduction In addition to surgery, many cancers are also treated with a combination of therapies involving cytotoxic chemotherapeutic drugs and/or radiation therapy. However, disadvantages to this method are that radiotherapeutic and chemotherapeutic agents are toxic to normal tissues, often have extremely high failure/remission rates and create lifethreatening side effects. This invention employs herpes simplex thymidine kinase (HSV TK)
gene as a suicide gene for tumor cell ablation in gene therapy. Technology description Thymidine kinase from Type 1 Herpes Simplex Virus thymidine kinase (HSVTK-1) is a salvage pathway enzyme which phosphorylates natural nucleoside substrates as well as nucleoside analogues. This protein may be utilized therapeutically by introducing it into a cell via a viral vector, followed by administration of a nucleoside analogue such as acyclovir or ganciclovir. HSVTK-1 then phosphorylates the nucleoside analogue, creating a toxic product capable of killing the host cell. Thus, use of retroviral vectors which express HSVTK- 1 has been suggested for not only the treatment of cancers, but for other diseases as well. The patent includes isolated nucleic acid molecules encoding a Herpes viridae 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. Business opportunity This technology can be used in cancer therapy and numerous other diseases. Cancer accounts for one-fifth of the total mortality in the United States, and is the second leading cause of death. Intellectual property position US patent has been issued and worldwide patents are pending.
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