title: TERT promoter-driven adenovirus vector for cancer gene therapy via systemic injection.
abstract: Adenovirus vectors (Adv) are used widely in cancer gene therapy research. However, the clinical application of Adv currently is limited to local, intratumoral administration; systemic administration leads to redundant transgene expression in the liver and subsequent hepatotoxicity. Here we replaced the conventional cytomegalovirus (CMV) promoter of Adv with a tumor-specific telomere reverse transcriptase (TERT) promoter, to restrict expression of the Adv-transduced transgene to tumor tissue alone. We evaluated the therapeutic and side effects after systemic administration of Adv expressing herpes simplex virus thymidine kinase (Ad-HSVtk) in mice bearing Meth-A tumors. Although systemically injected CMV promoter-driven Ad-HSVtk lacked therapeutic effect, mice injected with 2x10(11) viral particles containing TERT promoter-driven Ad-HSVtk showed inhibited tumor growth and prolonged survival with minimal side effects. Our results suggest that Adv in which transgene expression is driven by the TERT promoter are a promising prototype of tumor-targeting vectors for effective and safe cancer gene therapy.
authors: Department of Biotechnology and Therapeutics, Graduate School of Pharmaceutical Sciences, Osaka University, 1-6, Yamadaoka, Suita, Osaka 565-0871, Japan.
authors: Xinglei
authors: X
authors: Yao
authors: Yasuo
authors: Y
authors: Yoshioka
authors: Yusuke
authors: Y
authors: Eto
authors: Tomohiro
authors: T
authors: Morishige
authors: Yuka
authors: Y
authors: Okada
authors: Hiroyuki
authors: H
authors: Mizuguchi
authors: Yohei
authors: Y
authors: Mukai
authors: Naoki
authors: N
authors: Okada
authors: Shinsaku
authors: S
authors: Nakagawa
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D001835:Body Weight; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics; D006801:Humans; D007267:Injections; D051379:Mice; D008807:Mice, Inbred BALB C; D009374:Neoplasms, Experimental / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016019:Survival Analysis; D019098:Telomerase / Q000235:genetics*; D013997:Time Factors; D014162:Transfection
chemical_list: C509186:TERT protein, human; D019098:Telomerase