title: Suicide gene therapy using reducible poly (oligo-D-arginine) for the treatment of spinal cord tumors.
abstract: Suicide gene therapy based on a combination of herpes simplex virus-thymidine kinase (HSV-tk) and ganciclovir (GCV) has obstacles to achieving a success in clinical use for the treatment of cancer due to inadequate thymidine kinase (TK) expression. The primary concern for improving anticancer efficacy of the suicide gene therapy is to develop an appropriate carrier that highly expresses TK in vivo. Despite great advances in the development of non-viral vectors, none has been used in cancer suicide gene therapy, not even in experimental challenge. Reducible poly (oligo-D-arginine) (rPOA), one of the effective non-viral carriers working in vivo, was chosen to deliver HSV-tk to spinal cord tumors which are appropriate targets for suicide gene therapy. Since the system exerts toxicity only in dividing cells, cells in the central nervous system, which are non-proliferative, are not sensitive to the toxic metabolites. In the present study, we demonstrated that the locomotor function of the model rat was maintained through the tumor suppression resulting from the tumor-selective suicide activity by co-administration of rPOA/HSV-tk and GCV. Thus, rPOA plays a crucial role in suicide gene therapy for cancer, and an rPOA/HSV-tk and GCV system could help promote in vivo trials of suicide gene therapy.
authors.affiliation: Department of Bioengineering, College of Engineering, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Young-Wook
authors.initials: YW
authors.lastname: Won
authors.forename: Kyung-Min
authors.initials: KM
authors.lastname: Kim
authors.forename: Sung Su
authors.initials: SS
authors.lastname: An
authors.forename: Minhyung
authors.initials: M
authors.lastname: Lee
authors.forename: Yoon
authors.initials: Y
authors.lastname: Ha
authors.forename: Yong-Hee
authors.initials: YH
authors.lastname: Kim
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002470:Cell Survival / Q000187:drug effects; D004195:Disease Models, Animal; D004354:Drug Screening Assays, Antitumor; D015774:Ganciclovir / Q000494:pharmacology; D041722:Genes, Transgenic, Suicide; D015316:Genetic Therapy; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010084:Oxidation-Reduction / Q000187:drug effects; D010455:Peptides / Q000235:genetics* / Q000627:therapeutic use* / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D018139:Simplexvirus / Q000187:drug effects / Q000235:genetics; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D013120:Spinal Cord Neoplasms / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D013937:Thymidine Kinase / Q000378:metabolism; D014162:Transfection
chemical_list: D010455:Peptides; C015462:polyarginine; D013937:Thymidine Kinase; D015774:Ganciclovir