title: HSV-TK/GCV cancer suicide gene therapy by a designed recombinant multifunctional vector.
abstract: The objective of this research was to evaluate the efficacy of a recombinant nonviral vector for targeted delivery of a thymidine kinase (TK) suicide gene to xenograft SKOV-3 tumors. The vector was genetically engineered and used to condense the TK gene into particles of less than 100 nm. The nanoparticles were used to transfect and kill SKOV-3 cancer cells in combination with ganciclovir (GCV) in vitro. The results demonstrated that the vector could effectively kill up to 80% of the SKOV-3 cancer cells. In the next step, the ability of the vector to deliver the TK suicide gene to xenograft tumors of SKOV-3 was studied. The results demonstrated that the vector could transfect tumors and result in significant tumor size reduction during the period that GCV was administered. Administration of GCV for at least 3 weeks post transfection was of paramount importance. These results illustrate the therapeutic efficacy and application of a designed recombinant nonviral vector in cancer gene therapy.
  
  
  BACKGROUND
  A recombinant nonviral vector is used to deliver a suicide thymidine kinase gene under gancylovir control in vitro to SKOV-3 cancer cells with 70% efficiency. Follow on testing in a xenograft tumor demonstrated tumor reduction persisting for three weeks.
authors.affiliation: Department of Pharmaceutical Sciences, Center for Integrated Biotechnology, Washington State University, Pullman, Washington, USA.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Wang
authors.forename: Brenda F
authors.initials: BF
authors.lastname: Canine
authors.forename: Arash
authors.initials: A
authors.lastname: Hatefi
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy; D000818:Animals; D024221:Antineoplastic Protocols; D000998:Antiviral Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003131:Combined Modality Therapy; D015774:Ganciclovir / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D018259:Herpesvirus 1, Human / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D050997:Nanomedicine; D053758:Nanoparticles / Q000008:administration & dosage / Q000627:therapeutic use; D011355:Prodrugs / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use; D013937:Thymidine Kinase / Q000008:administration & dosage / Q000235:genetics / Q000627:therapeutic use*; D014162:Transfection; D023041:Xenograft Model Antitumor Assays
chemical_list: D000998:Antiviral Agents; D011355:Prodrugs; D013937:Thymidine Kinase; D015774:Ganciclovir
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