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Development of novel adenovirus vectors through the analysis of the virus with mammalian cells

Research Project

Project/Area Number 17H00863
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionOsaka University

Principal Investigator

Hiroyuki Mizuguchi  大阪大学, 薬学研究科, 教授 (50311387)

Project Period (FY) 2017-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥42,770,000 (Direct Cost: ¥32,900,000、Indirect Cost: ¥9,870,000)
Fiscal Year 2019: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Fiscal Year 2018: ¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Fiscal Year 2017: ¥11,570,000 (Direct Cost: ¥8,900,000、Indirect Cost: ¥2,670,000)
Keywordsウイルス / 遺伝子 / 癌 / 免疫学 / バイオテクノロジー
Outline of Final Research Achievements

In this study, we have done several basic studies about adenoviruses (Ad) in terms of viral replication, microRNA, immune responses, etc. And then, through such basic studies, we tried to develop several types of novel recombinant Ad vectors for gene therapy, vaccine, viral therapy, etc. We also developed novel Ad vectors having gene editing functions.

Academic Significance and Societal Importance of the Research Achievements

本研究は、Adと宿主の攻防を理解し、研究代表者が有する世界で最先端のAdベクター改変技術を駆使することで、新しい視点からベクター開発(改良)と関連する応用研究を進めるものであり、独創性が高く、学術的意義が大きい。また、日本独自の高性能ベクター開発は、その汎用性の観点から国益を考えたうえでも最重要研究課題の一つであり、その社会的意義は極めて大きい。

Report

(4 results)
  • 2020 Final Research Report ( PDF )
  • 2019 Annual Research Report
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (48 results)

All 2020 2019 2018 2017

All Journal Article (16 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 16 results,  Open Access: 12 results,  Acknowledgement Compliant: 2 results) Presentation (28 results) (of which Invited: 1 results) Book (2 results) Patent(Industrial Property Rights) (2 results) (of which Overseas: 2 results)

  • [Journal Article] Oncolytic Virus-Mediated Targeting of the ERK Signaling Pathway Inhibits Invasive Propensity in Human Pancreatic Cancer.2020

    • Author(s)
      Koujima T., Tazawa H., Ieda T., Araki H., Fushimi T., Shoji R., Kuroda S., Kikuchi S., Yoshida R., Umeda Y., Teraishi F., Urata Y., Mizuguchi H., Fujiwara T.
    • Journal Title

      Mol. Ther. Oncolysis.

      Volume: 17 Pages: 107-117

    • DOI

      10.1016/j.omto.2020.03.016

    • NAID

      120006869596

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Immune Modulation by Telomerase-Specific Oncolytic Adenovirus Synergistically Enhances Antitumor Efficacy with Anti-PD1 Antibody.2020

    • Author(s)
      Kanaya N., Kuroda S., Kakiuchi Y., Kumon K., Tsumura T., Hashimoto M., Morihiro T., Kubota T., Aoyama K., Kikuchi S., Nishizaki M., Kagawa S., Tazawa H., Mizuguchi H., Urata Y., Fujiwara T.
    • Journal Title

      Mol. Ther.

      Volume: 28 Issue: 3 Pages: 794-804

    • DOI

      10.1016/j.ymthe.2020.01.003

    • NAID

      120006952300

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of a novel oncolytic adenovirus expressing a short-hairpin RNA against Cullin 4A.2020

    • Author(s)
      Wakabayashi K., Sakurai F., Ono R., Fujiwara T., Mizuguchi H.
    • Journal Title

      Anticancer Res.

      Volume: 40 Issue: 1 Pages: 161-168

    • DOI

      10.21873/anticanres.13937

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Efficient generation of adenovirus vectors carrying the Clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR associated proteins (Cas)12a system by suppressing Cas12a expression in packaging cells.2019

    • Author(s)
      Tsukamoto T., Sakai E., Nishimae F., Sakurai F., Mizuguchi H.
    • Journal Title

      J. Biotech.

      Volume: 304 Pages: 1-9

    • DOI

      10.1016/j.jbiotec.2019.08.004

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Adenovirus Fiber can Distribute Itself to the Cell Surface without Membrane Damage.2019

    • Author(s)
      Sato A., Hirai T., Koizumi N., Hatakeyama S., Watanabe A., Nomura T., Sakurai F., Mizuguchi H., Utoguchi N.
    • Journal Title

      BPB Reports

      Volume: 2 Pages: 113-118

    • NAID

      130007940517

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A MicroRNA Derived from Adenovirus Virus-Associated RNAII Promotes Virus Infection via Posttranscriptional Gene Silencing.2019

    • Author(s)
      Wakabayashi K., Machitani M., Tachibana M., Sakurai F., Mizuguchi H.
    • Journal Title

      J. Virol.

      Volume: 93 Issue: 2

    • DOI

      10.1128/jvi.01265-18

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A Flow Cytometry-Based Method to Determine the Titer of Adenoviruses Expressing an Extraneous Gene2018

    • Author(s)
      Asada A., Hayakawa H., Yanase N., Abe K., Sakurai F., Mizuguchi H., Urata Y.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 41 Issue: 10 Pages: 1615-1619

    • DOI

      10.1248/bpb.b18-00316

    • NAID

      130007492909

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2018-10-01
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Generation of the Adenovirus Vector-Mediated CRISPR/Cpf1 System and the Application for Primary Human Hepatocytes Prepared from Humanized Mice with Chimeric Liver2018

    • Author(s)
      Tsukamoto T., Sakai E., Iizuka S., Taracena-Gandar M., Sakurai F., Mizuguchi H.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 41 Issue: 7 Pages: 1089-1095

    • DOI

      10.1248/bpb.b18-00222

    • NAID

      130007387204

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2018-07-01
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Antibodies against adenovirus fiber and penton base proteins inhibit adenovirus vector-mediated transduction in the liver following systemic administration.2018

    • Author(s)
      Tomita K., Sakurai F., Iizuka S., Hemmi M., Wakabayashi K., Tachibana M., Katayama K., Kamada H., Mizuguchi H.
    • Journal Title

      Sci. Rep.

      Volume: 8 Issue: 1 Pages: 12315-12315

    • DOI

      10.1038/s41598-018-30947-z

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Clinical features of squamous cell lung cancer with anaplastic lymphoma kinase (ALK)-rearrangement: a retrospective analysis and review.2018

    • Author(s)
      Watanabe J, Togo S, Sumiyoshi I, Namba Y, Suina K, Mizuno T, Kadoya K, Motomura H, Iwai M, Nagaoka T, Sasaki S, Hayashi T, Uekusa T, Abe K, Urata Y, Sakurai F, Mizuguchi H, Kato S, Takahashi K.
    • Journal Title

      Oncotarget

      Volume: 9(35) Issue: 35 Pages: 24000-24013

    • DOI

      10.18632/oncotarget.25257

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Detection of circulating tumor cells in cervical cancer using a conditionally2017

    • Author(s)
      Takakura M, Matsumoto T, Nakamura M, Mizumoto Y, Myojyo S, Yamazaki R, Iwadare
    • Journal Title

      Cancer Sci.ence

      Volume: 109(1) Issue: 1 Pages: 231-240

    • DOI

      10.1111/cas.13449

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Th17 Promotes Induction of antigen-specific gut-mucosal CTLs following adenovirus vector vaccination.2017

    • Author(s)
      Hemmi M., Tachibana M.,, Fujimoto N., Shoji M., Sakurai F., Kobiyama K., Ishii K.J., Akira S., Mizuguchi H.
    • Journal Title

      Front Immunol.

      Volume: 8 Pages: 1456-1456

    • DOI

      10.3389/fimmu.2017.01456

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Suppression of oncolytic adenovirus-mediated hepatotoxicity by liver-specific inhibition of NF-κB.2017

    • Author(s)
      Machitani M., Sakurai F., Wakabayashi K., Nakatani K., Tachibana M., Kato N., Fujiwara T., Mizuguchi H.
    • Journal Title

      Mol. Ther. Oncolysis.

      Volume: 7 Pages: 76-85

    • DOI

      10.1016/j.omto.2017.10.003

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Neonatal gene therapy for hemophilia B by a novel adenovirus vector showing sustained transgene expression via a reduction in the leaky expression of viral genes.2017

    • Author(s)
      Iizuka S., Sakurai F., Tachibana M., Ohashi K., Mizuguchi H.
    • Journal Title

      Mol. Ther. Methods. Clin. Dev.

      Volume: 6 Pages: 183-193

    • DOI

      10.1016/j.omtm.2017.07.001

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] MicroRNA miR-27 Inhibits Adenovirus Infection by Suppressing the Expression of SNAP25 and TXN2.2017

    • Author(s)
      Machitani M, Sakurai F, Wakabayashi K, Nakatani K, Tachibana M, Mizuguchi H
    • Journal Title

      Journalof Virology

      Volume: 印刷中 Issue: 12

    • DOI

      10.1128/jvi.00159-17

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Inhibition of CRISPR/Cas9-Mediated Genome Engineering by a Type I Interferon-Induced Reduction in Guide RNA Expression2017

    • Author(s)
      Machitani M., Sakurai F., Wakabayashi K., Nakatani K., Takayama K., Tachibana M., Mizuguchi H.
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 40 Issue: 3 Pages: 272-277

    • DOI

      10.1248/bpb.b16-00700

    • NAID

      130005398474

    • ISSN
      0918-6158, 1347-5215
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 35型アデノウイルスを基盤とした新規腫瘍溶解性ウイルスの開発と機能評価2020

    • Author(s)
      小野良輔、高山耕輔、櫻井文教、水口裕之
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 末梢循環腫瘍細胞の高感度な検出に向けた制限増殖型アデノウイルスの改良2020

    • Author(s)
      池本星南、櫻井文教、高山耕輔、岡部隆宏、十合晋作、水口裕之
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] プロモーター改変による高力価CRISPR-LbCas12a搭載アデノウイルスベクターの作製2019

    • Author(s)
      塚本智仁、酒井英子、西前文敬、櫻井文教、水口裕之
    • Organizer
      第66回日本生化学会近畿支部例会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Cas12aの発現はアデノウイルスベクターの産生を阻害する2019

    • Author(s)
      塚本智仁、酒井英子、西前文敬、櫻井文教、水口裕之
    • Organizer
      日本ゲノム編集学会第4回大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] アデノウイルスベクターを用いたFc融合型血液凝固第IX因子の過剰発現による胎児期血友病治療に関する検討2019

    • Author(s)
      櫻井文教、飯塚俊輔、大橋一夫、水口裕之
    • Organizer
      第35回日本DDS学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 35型アデノウイルスを基盤とした新規腫瘍溶解性アデノウイルスの開発2019

    • Author(s)
      池本星南、高山耕輔、櫻井文教、水口裕之
    • Organizer
      第35回日本DDS学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ウイルス遺伝子の発現抑制により高い安全性と長期的な遺伝子発現を可能にした改良型アデノウイルスベクターの開発2019

    • Author(s)
      櫻井文教、清水かほり、飯塚俊輔、塚本智仁、西前文敬、酒井英子、高山和雄、石田雄二、立野(向谷)知世、茶山一彰、水口裕之
    • Organizer
      第15回広島肝臓プロジェクト研究センター
    • Related Report
      2019 Annual Research Report
  • [Presentation] CRISPR-Cas12a搭載アデノウイルスベクターによるゲノム編集2019

    • Author(s)
      塚本智仁、酒井英子、西前文敬、石田雄二、立野(向谷)知世、茶山一彰、櫻井文教、水口裕之
    • Organizer
      第15回広島肝臓プロジェクト研究センター
    • Related Report
      2019 Annual Research Report
  • [Presentation] 35型アデノウイルスを基盤とした新規腫瘍溶解性アデノウイルスの開発2019

    • Author(s)
      小野良輔、高山耕輔、池本星南、櫻井文教、水口裕之
    • Organizer
      第69回日本薬学会関西支部総会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Adenovirus vector-induced hepatotoxicity during the early phase after systemic administration is attributed to IL-6-induced leaky expression of adenovirus genes2019

    • Author(s)
      Sakurai F., Shimizu K., Iizuka S., Ono R., Tsukamoto T., Nakamura SI., Nishinaka T., Terada T., Mizuguchi H.
    • Organizer
      第67回日本ウイルス学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] ヒト35型アデノウイルスを基盤とした新規腫瘍溶解性ウイルスの機能評価2019

    • Author(s)
      小野良輔、高山耕輔、櫻井文教、水口裕之、ヒト35型アデノウイルスを基盤とした新規腫瘍溶解性ウイルスの機能評価
    • Organizer
      第4回日本遺伝子細胞治療学会 若手研究会セミナー
    • Related Report
      2019 Annual Research Report
  • [Presentation] 腫瘍溶解性アデノウイルスにおけるE1遺伝子発現カセットの最適化に関する検討2019

    • Author(s)
      西前文敬、高山耕輔、櫻井文教、水口裕之
    • Organizer
      第4回日本遺伝子細胞治療学会 若手研究会セミナー
    • Related Report
      2019 Annual Research Report
  • [Presentation] Cas12aタンパク発現制御によるCRISPR-Cas12aシステム搭載アデノウイルスベクター作製技術の開発2019

    • Author(s)
      塚本智仁、酒井英子、西前文敬、櫻井文教、水口裕之
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 高タイターCpf1発現アデノウイルスベクターの作製2019

    • Author(s)
      塚本智仁、酒井英子、櫻井文教、水口裕之
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ゲノム編集技術を利用したアデノウイルスベクターの新規改変法の開発2019

    • Author(s)
      西前文敬、若林圭作、塚本智仁、櫻井文教、水口裕之
    • Organizer
      日本薬学会第139年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] CRISPR/Cpf1搭載アデノウイルスベクターの作製とヒト肝細胞キメラマウス由来肝細胞への適用2018

    • Author(s)
      塚本智仁、酒井英子、櫻井文教、水口裕之
    • Organizer
      第65回日本生化学会近畿支部例会
    • Related Report
      2018 Annual Research Report
  • [Presentation] CRISPR/Cpf1搭載アデノウイルスベクターの作製2018

    • Author(s)
      塚本智仁、酒井英子、櫻井文教、水口裕之
    • Organizer
      日本ゲノム編集学会第3回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Suppression of oncolytic adenovirus-mediated hepatotoxicity by liver-specific inhibition of NF-kB2018

    • Author(s)
      Machitani M., Sakurai F., Wakabayashi K., Tachibana M., Kato N., Fujiwara T., Mizuguchi H.
    • Organizer
      第24回日本遺伝子細胞治療学会学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] アデノウイルスが発現するVA-RNAIIは、microRNAの前駆体としてAdの増殖に寄与する2018

    • Author(s)
      若林圭作、町谷充洋、櫻井文教、水口裕之
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] アデノウイルスと遺伝子治療、ウイルス療法2018

    • Author(s)
      水口裕之
    • Organizer
      第17回日本再生医療学会総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 高性能な腫瘍溶解性アデノウイルスの開発に向けたE1遺伝子発現カセットの最適化に関する検討2018

    • Author(s)
      高山耕輔、若林圭作、櫻井文教、水口裕之
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] CRISPR/Cpf1搭載アデノウイルスベクターによるゲノム編集効率の評価2018

    • Author(s)
      塚本智仁、酒井英子、高山和雄、櫻井文教、水口裕之
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 新規Adベクターによる血友病新生児に対する遺伝子治療効果の検討2017

    • Author(s)
      飯塚俊輔、櫻井文教、立花雅史、大橋一夫、水口裕之、
    • Organizer
      第17回シンポジウム遺伝子デリバリー研究会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 肝臓特異的なマイクロRNAを利用して肝障害性を低減させた新規アデノウイルスベクターによる血友病遺伝子治療に関する検討2017

    • Author(s)
      飯塚俊輔、櫻井文教、立花雅史、大橋一夫、水口裕之
    • Organizer
      第33回日本DDS学会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Neonatal gene therapy for hemophilia B by a novel adenovirus vector showing sustained transgene expression via a reduction in the leaky expression of Ad genes2017

    • Author(s)
      Shunsuke Iizuka, Fuminori Sakurai, Masashi Tachibana, Kazuo Ohashi, Hiroyuki Mizuguchi
    • Organizer
      第23回日本遺伝子細胞治療学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Promotion of adenovirus infection by a microRNA derived from adenovirus Virus-Associated RNA II2017

    • Author(s)
      K. Wakabayashi, M. Machitani, M. Tachibana, F. Sakurai, H. Mizuguchi
    • Organizer
      第23回日本遺伝子細胞治療学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Truncated form of virus-associated RNA II, mivaRNA II, promotes adenovirus replication in a post-transcriptional gene silencing manner2017

    • Author(s)
      K. Wakabayashi, M. Machitani, M. Tachibana, F. Sakurai, H. Mizuguchi
    • Organizer
      第65回日本ウイルス学会学術集会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Th17 promotes the induction of antigen-specific gut-mucosal CTLs following intramuscular vaccination of an adenovirus vector,2017

    • Author(s)
      Hemmi M., Tachibana M., Fujimoto N., Shoji M., Sakurai F., Kobiyama K., Ishii K. J., Akira S., Mizuguchi H.
    • Organizer
      第46回日本免疫学会学術集会,
    • Related Report
      2017 Annual Research Report
  • [Book] ドラッグデリバリーシステム-バイオ医薬品創成に向けた組織、細胞内、核内送達技術の開発- (担当:分担執筆, 範囲:第22 章  粘膜免疫誘導型ワクチンとしてのアデノウイルスベクター)2018

    • Author(s)
      立花雅史、邊見昌久、水口裕之
    • Total Pages
      260
    • Publisher
      CMC出版
    • ISBN
      9784781313337
    • Related Report
      2018 Annual Research Report
  • [Book] バイオロジクスの開発と品質・安全性確保 下巻 (担当:分担執筆, 範囲:第2章第1節  アデノウイルスベクター)2018

    • Author(s)
      水口裕之・早川堯夫
    • Total Pages
      504
    • Publisher
      エル・アイ・シー出版
    • ISBN
      9784900487574
    • Related Report
      2018 Annual Research Report
  • [Patent(Industrial Property Rights)] 腫瘍溶解性ヒト35型アデノウイルス2020

    • Inventor(s)
      水口裕之、櫻井文教
    • Industrial Property Rights Holder
      水口裕之、櫻井文教
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Related Report
      2019 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 腫瘍溶解性ヒト35型アデノウイルス2019

    • Inventor(s)
      水口裕之、櫻井文教
    • Industrial Property Rights Holder
      大阪大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2019
    • Related Report
      2018 Annual Research Report
    • Overseas

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Published: 2017-04-28   Modified: 2022-01-27  

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