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Development of novel anti-viral treatment using primary human hepatocyte and stable isotope.

Research Project

Project/Area Number 15K15293
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Gastroenterology
Research InstitutionHiroshima University

Principal Investigator

CHAYAMA KAZUAKI  広島大学, 医歯薬保健学研究院(医), 教授 (00211376)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsB型肝炎ウイルス / ヒト肝細胞 / キメラマウス / Hepg2 / NTCP / HepaRG / HepG2
Outline of Final Research Achievements

We administered mouse food that is used to make stable isotope containing diet. uPA-scid based mouse did not eat this food and weakened. Thus it became clear to create stable isotope labelled primary hepatocyte using this diet. As the diet is quite expensive and difficult to purchase a different diet, we decided to make a different strain of human hepatocyte chimeric mouse. We attempted to establish a human hepatocyte chimeric mouse using different immune deficient mouse strain and succeeded to establish enough human hepatocyte chimerism. We also confirmed to establish stable hepatitis B and hepatitis C virus viremia using this human hepatocyte chimeric mouse. We will try to feed this mouse with stable isotope labelled diet and create labelled primary human hepatocytes.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (20 results)

All 2017 2016 2015 Other

All Journal Article (11 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 10 results,  Open Access: 10 results,  Acknowledgement Compliant: 6 results) Presentation (7 results) (of which Int'l Joint Research: 4 results,  Invited: 2 results) Remarks (2 results)

  • [Journal Article] Interferon stimulated genes and innate immune activation following infection with hepatitis B and C viruses.2017

    • Author(s)
      Hayes CN, Chayama K.
    • Journal Title

      J Med Virol.

      Volume: 89 Issue: 3 Pages: 388-396

    • DOI

      10.1002/jmv.24659

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The relationship between HBcrAg and HBV reinfection in HBV related post-liver transplantation patients.2017

    • Author(s)
      Urabe A, Imamura M, Tsuge M, Kan H, Fujino H, Fukuhara T, Masaki K, Kobayashi T, Ono A, Nakahara T, Kawaoka T, Hiramatsu A, Kawakami Y, Aikata H, Hayes CN, Maki N, Ohdan H, Chayama K.
    • Journal Title

      J Gastroenterol.

      Volume: 52 Issue: 3 Pages: 366-375

    • DOI

      10.1007/s00535-016-1240-y

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Interferon-stimulated gene of 20 kDa protein (ISG20) degrades RNA of Hepatitis B virus to impede the replication of HBV in vitro and in vivo.2016

    • Author(s)
      Leong CR, Funami K, Oshiumi H, Mengao D, Takaki H, Matsumoto M, Aly HH, Watashi K, Chayama K, Seya T.
    • Journal Title

      Oncotarget.

      Volume: 7 Issue: 42 Pages: 68179-68193

    • DOI

      10.18632/oncotarget.11907

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Antiviral effects of anti-HBs immunoglobulin and vaccine on HBs antigen seroclearance for chronic hepatitis B infection.2016

    • Author(s)
      Tsuge M, Hiraga N, Uchida T, Kan H, Miyaki E, Masaki K, Ono A, Nakahara T, Abe-Chayama H, Zhang Y, Naswa MG, Kawaoka T, Miki D, Imamura M, Kawakami Y, Aikata H, Ochi H, Hayes CN, Chayama K.
    • Journal Title

      Journal of Gastroenterology

      Volume: In press Issue: 11 Pages: 1073-1080

    • DOI

      10.1007/s00535-016-1189-x

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Highly multiplexed CRISPR-Cas9-nuclease and Cas9-nickase vectors for inactivation of hepatitis B virus.2016

    • Author(s)
      Sakuma T, Masaki K, Abe-Chayama H, Mochida K, Yamamoto T, Chayama K.
    • Journal Title

      Genes Cells.

      Volume: 21 Issue: 11 Pages: 1253-1262

    • DOI

      10.1111/gtc.12437

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Novel pH-sensitive multifunctional envelope-type nanodevice for siRNA-based treatments for chronic HBV infection2016

    • Author(s)
      Yamamoto, N. Sato, Y. Munakata, T. Kakuni, M. Tateno, C. Sanada, T. Hirata, Y. Murakami, S. Tanaka, Y. Chayama, K. Hatakeyama, H. Hyodo, M. Harashima, H. Kohara, M.
    • Journal Title

      Journal of hepatology

      Volume: 64 Issue: 3 Pages: 547-455

    • DOI

      10.1016/j.jhep.2015.10.014

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] RNA exosome complex regulates stability of Hepatitis B Virus's X-mRNA transcript in a Non-Stop mediated (NSD) RNA quality control mechanism.2016

    • Author(s)
      Hussein H. Aly, Junya Suzuki, Koichi Watashi, Kazuaki Chayama, Shin-ichi Hoshino, Makoto Hijikata, Takanobu Kato, and Takaji Wakita
    • Journal Title

      J Biol Chem

      Volume: 291 Issue: 31 Pages: 15958-15974

    • DOI

      10.1074/jbc.m116.724641

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Elimination of HCV via a non-ISG-mediated mechanism by vaniprevir andBMS-788329 combination therapy in human hepatocyte chimeric mice.2016

    • Author(s)
      Uchida T, Hiraga N, Imamura M, Yoshimi S, Kan H, Miyaki E, Tsuge M, Abe H, Hayes CN, Aikata H, Ishida Y, Tateno C, Ellis JD, Chayama K.
    • Journal Title

      Virus Res.

      Volume: 213 Issue: 1 Pages: 62-68

    • DOI

      10.1016/j.jinf.2015.09.038

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Early events in hepatitis B virus infection: From the cell surface to the nucleus.2016

    • Author(s)
      Hayes CN, Zhang Y, Makokha GN, Hasan MZ, Omokoko MD, Chayama K.
    • Journal Title

      Journal of Gastroenterology and Hepatology

      Volume: Volume 31, Issue 2, Issue: 2 Pages: 302-309

    • DOI

      10.1111/jgh.13175

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] HBV culture and infectious systems.2016

    • Author(s)
      Hayes CN, Chayama K.
    • Journal Title

      Hepatology International

      Volume: 無し Issue: 4 Pages: 559-566

    • DOI

      10.1007/s12072-016-9712-y

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Development of new therapies using an animal model of hepatitis virus infection(肝炎ウイルスの動物モデルと治療開発)2015

    • Author(s)
      Chayama K, Imamura M.
    • Journal Title

      Nihon Rinsho.(日本臨床2015年増刊号 新ウイルス性肝炎学)

      Volume: 無し

    • Related Report
      2015 Research-status Report
  • [Presentation] Targeting Host and Viral Interactions: Insights from Mice Model2017

    • Author(s)
      Kazuaki Chayama
    • Organizer
      Asian Pacific Association for the Study of the Liver 2017(APASL 2017) (アジア太平洋肝臓病学会議)
    • Place of Presentation
      上海(中国)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] A mouse model of human CTL mediated severe acute hepatitis B2016

    • Author(s)
      茶山 一彰
    • Organizer
      第52回日本肝臓学会総会 特別企画1-JSH主催EASL Joint Meeting
    • Place of Presentation
      幕張
    • Related Report
      2016 Annual Research Report
  • [Presentation] B型肝炎2016

    • Author(s)
      茶山 一彰
    • Organizer
      第52回日本肝臓学会総会前期教育講演会
    • Place of Presentation
      幕張
    • Related Report
      2016 Annual Research Report
  • [Presentation] Best Strategy for Curing HCV Genotype 1 and 4: East vs. West2016

    • Author(s)
      Kazuaki Chayama
    • Organizer
      2016 APASL Single Topic Conference on Hepatitis C
    • Place of Presentation
      高雄(台湾)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Integrated safety and Tolerability of DCV+ASV in Patients with Chronic HCV Genotype 1b Infection2016

    • Author(s)
      Kazuaki Chayama
    • Organizer
      2016 APASL Single Topic Conference on Hepatitis C
    • Place of Presentation
      高雄(台湾)
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] B型慢性肝炎治療の軌跡2016

    • Author(s)
      茶山 一彰
    • Organizer
      第20回日本肝臓学会大会
    • Place of Presentation
      神戸
    • Related Report
      2016 Annual Research Report
  • [Presentation] Recent Progress in Treatment for Chronic Hepatitis C2016

    • Author(s)
      茶山 一彰
    • Organizer
      2016アジア太平洋消化器病週間(APDW2016)
    • Place of Presentation
      神戸
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Remarks] 広島大学病院消化器・代謝内科ホームページ

    • URL

      http://shounai.hiroshima-u.ac.jp/liver.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 広島大学病院消化器・代謝内科ホームページ

    • URL

      http://home.hiroshima-u.ac.jp/naika1/research_profile/liver_lab/

    • Related Report
      2015 Research-status Report

URL: 

Published: 2015-04-16   Modified: 2018-03-22  

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