Development of an adenovirus vector containing microRNA-regulated gene expression system

2010 Fiscal Year Final Research Report

• Project/Area Number: 20689004
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Medical pharmacy
• Research Institution: National Institute of Biomedical Innovation
• Principal Investigator: SAKURAI Fuminori National Institute of Biomedical Innovation, 大学院・薬学研究科, 准教授 (70370939)
• Research Collaborator: MIZUGUCHI Hiroyuki 大阪大学, 大学院・薬学研究科, 教授 ; KAWABATA Kenji (独)医薬基盤研究所, 幹細胞制御プロジェクト, プロジェクトリーダー ; KATAYAMA Kazufumi 大阪大学, 大学院・薬学研究科, 助教 ; TASHIRO Katsuhisa (独)医薬基盤研究所, 幹細胞制御プロジェクト, プロジェクト研究員 ; KONDOH Masuo 大阪大学, 大学院・薬学研究科, 准教授 ; YAGI Kiyohito 大阪大学, 大学院・薬学研究科, 教授 ; NAKAMURA Shin-ichiro 滋賀医科大学, 動物生命科学センター, 准教授 ; KAWASE Atsushi 近畿大学, 薬学部, 講師 ; IWAKI Masahiro 近畿大学, 薬学部, 教授 ; HAYAKAWA Takao 近畿大学, 薬学総合研究所, 所長 ; FUJIWARA Toshiyoshi 岡山大学, 医歯薬学総合研究科, 教授 ; SUZUKI Takayuki 大阪大学, 大学院・薬学研究科, 大学院生 ; SUGIO Kumiko 大阪大学, 大学院・薬学研究科, 大学院生 ; SHIMIZU Kahori 大阪大学, 大学院・薬学研究科, 大学院生 ; BENNETT David Mark Gilfedder 大阪大学, 大学院・薬学研究科, 大学院生 ; TOMITA Kyoko 大阪大学, 大学院・薬学研究科, 大学院生
• Project Period (FY): 2008 – 2010
• Keywords: 遺伝子治療 / マイクロRNA / 発現制御 / 遺伝子導入ベクター

Research Abstract

In this study, we developed the adenovirus (Ad) vectors which exhibited enhanced safety profiles by incorporating microRNA (miRNA)-regulated gene expression system. For example, (1)an Ad vector which shows reduction in the transgene expression in the liver and spleen by insertion of sequences complementary to liver- and spleen-specific miRNA, respectively, (2) an Ad vector which exhibits reduction in the leaky expression of Ad genes by insertion of miRNA complementary sequences into 3'-untranslated region of E2A or E4 genes, (3) a oncolytic Ad which shows reduced replication in normal cells by insertion of sequences complementary to normal cell-specific miRNAs, were developed.

Research Products

• [Journal Article] Enhanced Safety Profiles of the Telomerase-Specific Replication- Competent Adenovirus by Incorporation of Normal Cell-Specific microRNA-Targeted Sequences. (2011)
  • Author(s): Sugio K, Sakurai F, Katayama K, Tashiro K, Matsui H, Kawabata K, Kawase A, Iwaki M, Hayakawa T, Fujiwara T, Mizuguchi H
  • Journal Title: Clin Cancer Res. 17 Pages: 2807-2818
• [Journal Article] Development of cellular and gene therapy products for bioacitve protein-based therapy. (2010)
  • Author(s): Sakurai F, Nishikawa M.
  • Journal Title: Yakugaku Zasshi. 130 Pages: 1487-1488
• [Journal Article] Development of recombinant adenovirus carrying microRNA-regulated gene expression system. (2010)
  • Author(s): Sakurai F, Mizuguchi H
  • Journal Title: Yakugaku Zasshi. 130 Pages: 1497-1504
• [Journal Article] 遺伝子組換えウイルスの安全性向上に向けた遺伝子改変-microRNAによる遺伝子発現制御システムを搭載した組換えウイルスの開発- (2009)
  • Author(s): 櫻井文教、川端健二、水口裕之
  • Journal Title: Drug Delivery System. 24 Pages: 572-581
• [Journal Article] miR-122a-regulated expression of a suicide gene prevents hepatotoxicity without altering antitumor effects in suicide gene therapy. (2008)
  • Author(s): Suzuki T, Sakurai F, Nakamura S, Kouyama E, Kawabata K, Kondoh M, Yagi K, Mizuguchi H
  • Journal Title: Mol Ther. 16 Pages: 1719-1726
• [Journal Article] MicroRNA-regulated Transgene Expression Systems for Gene Therapy and Virotherapy.
  • Author(s): Sakurai F, Katayama K, Mizuguchi H
  • Journal Title: Frontier in Bioscience. (in press.)
• [Journal Article] ウイルスベクターと遺伝子治療
  • Author(s): 水口裕之、櫻井文教
  • Journal Title: 化学療法の領域 (印刷中)
• [Presentation] Recombinant adenoviruses carrying microRNA-regulated gene expression system. (2010)
  • Author(s): Sakurai F
  • Organizer: The 9th China-Japan-Korea Foresight Joint Symposium on Gene Delivery and the International Workshop on Biomaterials 2010.
  • Place of Presentation: China
  • Year and Date: 2010-06-21
• [Presentation] マイクロRNAによる遺伝子発現制御システムを搭載した組換えアデノウイルスの開発 (2010)
  • Author(s): 櫻井文教、水口裕之
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-30
• [Presentation] MiRNA-regulated expression of herpes simplex virus thymidine kinase prevents hepatotoxicity without disturbing antitumor effect in adenovirus vector-mediated suicide gene therapy. (2008)
  • Author(s): Sakurai F, Suzuki T, Nakamura S, Kouyama E, Kondoh M, Yagi K, Kawabata K, Mizuguchi H.
  • Organizer: 第14回日本遺伝子治療学会学術集会
  • Place of Presentation: 札幌
  • Year and Date: 20080612-20080614
• [Presentation] MicroRNA-regulated transgene expression system reduces unwanted side effects in adenovirus vector-mediated suicide gene therapy. (2008)
  • Author(s): Sakurai F, Suzuki T, Kondoh M, Yagi K, Kawabata K, Mizuguchi H.
  • Organizer: 11^<th> Annual Meeting of the American Society of Gene Therapy.
  • Place of Presentation: Boston, USA
  • Year and Date: 20080528-20080601
• [Remarks] ホームページ等
  • URL: https://sites.google.com/site/bunshiseibutugaku/