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Development immunomodulative drug based on the recognition mechanism of viral B-DNA.

Research Project

Project/Area Number 20200074
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research a proposed research project)

Allocation TypeSingle-year Grants
Research Field Virology
Environmental pharmacy
Research InstitutionYokohama City University

Principal Investigator

TAKESHITA Fumihiko  Yokohama City University, 医学研究科, 客員教授 (60333572)

Project Period (FY) 2008 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥32,630,000 (Direct Cost: ¥25,100,000、Indirect Cost: ¥7,530,000)
Fiscal Year 2010: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Fiscal Year 2009: ¥10,660,000 (Direct Cost: ¥8,200,000、Indirect Cost: ¥2,460,000)
Fiscal Year 2008: ¥11,310,000 (Direct Cost: ¥8,700,000、Indirect Cost: ¥2,610,000)
Keywords感染防御 / 分子 / 基礎医学 / ヒストン / 自然免疫 / 免疫調節薬
Research Abstract

Previous our data have discovered the novel H2B function to recognize non-chromosomal double stranded DNA (dsDNA), and induce antiviral innate immune response. In current research, we constructed the fusion protein, named as N'-CARD, by fusion of IPS-1 fragment with H2B fragment, and found that N'-CARD induced type I interferons (Type I IFNs) production. In addition, nuclear DNA helicase II was identified as N'-CARD associated molecules, and was indispensable for N'-CARD-mediated innate immune response. Furthermore, N'-CARD fused to protein transduction domain (N'-CARD-PTD) is a candidate of novel adjuvant. Therefore, current research revealed H2B-sensing machinery of cytoplasmic dsDNA as well as novel adjuvant candidate for vaccine development.

Report

(4 results)
  • 2010 Annual Research Report   Final Research Report ( PDF )
  • 2009 Annual Research Report
  • 2008 Annual Research Report
  • Research Products

    (22 results)

All 2011 2010 2009 2008

All Journal Article (15 results) (of which Peer Reviewed: 7 results) Presentation (4 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] NLRP4 negatively regulates autophagic processes through an association with beclin1.2011

    • Author(s)
      Nao Jounai
    • Journal Title

      Journal of immunology

      Volume: 186 Pages: 1646-1655

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modulation of intracellular signaling using protein-transduction technology.2010

    • Author(s)
      Kobiyama, K., N. Jounai, K.J.Ishii, T.Horii,K.Suzuki, A.Ryo, F.Takeshita.
    • Journal Title

      Crit Rev Immunol 30

      Pages: 395-421

    • Related Report
      2010 Final Research Report
  • [Journal Article] Immunogenicity of whole-parasite vaccines against Plasmodium falciparum involves malarial hemozoin and host TLR9.2010

    • Author(s)
      Coban, C., Y. Igari, M. Yagi, T.Reimer, S.Koyama, T.Aoshi, K.Ohata, T.Tsukui, F.Takeshita, K.Sakurai, T.Ikegami, A.Nakagawa, T.Horii, G.Nunez, K.J.Ishii, S.Akira.
    • Journal Title

      Cell Host Microbe 7

      Pages: 50-61

    • Related Report
      2010 Final Research Report
  • [Journal Article] Extrachromosomal histone H2B mediates innate antiviral immune responses induced by intracellular double-stranded DNA.2010

    • Author(s)
      Kobiyama, K., F.Takeshita, N.Jounai, A.Sakaue-Sawano, A.Miyawaki, K.J.Ishii, T.Kawai, S.Sasaki, H.Hirano, N.Ishii, K.Okuda, K.Suzuki.
    • Journal Title

      J Virol 84

      Pages: 822-832

    • Related Report
      2010 Final Research Report
  • [Journal Article] Mutant mouse p53 transgene elevates the chemical induction of tumors that respond to gene silencing with siRNA.2010

    • Author(s)
      Tanooka, H., K.Tatsumi, H.Tsuji, Y.Noda, T.Katsube, H.Ishii, A.Ootsuyama, F.Takeshita, T.Ochiya.
    • Journal Title

      Cancer Gene Ther 17

      Pages: 1-10

    • Related Report
      2010 Final Research Report
  • [Journal Article] C/EBPδ and STAT-1 Are Required for TLR8 Transcriptional Activity2010

    • Author(s)
      Claudia Zannetti
    • Journal Title

      Journal of Biological Chemistry

      Volume: 285 Pages: 34773-34780

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Modulation of intracellular signaling using protein-transduction technology2010

    • Author(s)
      Kouji Kobiyama
    • Journal Title

      Critical Reviews Immunology

      Volume: 30 Pages: 395-421

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Extrachromosomal histome H2B mediates innate antiviral immune resp-onses induced by intracellular double-stranded DNA.2010

    • Author(s)
      小檜山康司
    • Journal Title

      Journal of Virology 84号

      Pages: 822-832

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Immunogeneicity of Whole-Parasite Vaccine against Plasmjodium falcipa-rum involves Mararial Hemozoin and Host TLR9.2010

    • Author(s)
      Cevayir Coban
    • Journal Title

      Cell Host & Microbe 7号

      Pages: 50-61

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Tryptophan aspartate-containing coat protein (CORO1A) suppresses Toll-like receptor signalling in Mycobacterium leprae infection.2009

    • Author(s)
      Tanigawa, K., K.Suzuki, H.Kimura, F.Takeshita, H.Wu, T.Akama, A.Kawashima, N.Ishii.
    • Journal Title

      Clin Exp Immunol 156

      Pages: 495-501

    • Related Report
      2010 Final Research Report
  • [Journal Article] A signaling polypeptide derived from an innate immune adaptor molecule can be harnessed as a new class of vaccine adjuvant.2009

    • Author(s)
      Kobiyama, K., F.Takeshita, K.J.Ishii, S.Koyama, T.Aoshi, S.Akira, A.Sakaue-Sawano, A.Miyawaki, Y.Yamanaka, H.Hirano, K.Suzuki, K.Okuda.
    • Journal Title

      J Immunol 182

      Pages: 1593-1601

    • Related Report
      2010 Final Research Report
  • [Journal Article] A signaling polypeptide derived from an innate immune adaptor molecule can be harnessed as a new class of vaccine adjuvant2009

    • Author(s)
      Kobiyama K, Takeshita F*, Ishii KJ, Koyama S, Aoshi T, Akira S, Sakaue-Sawano A, Miyawaki A, Yamanaka Y, Hirano H, Suzuki K, and Okuda K.
    • Journal Title

      Journal of Immunology 182

      Pages: 1593-1601

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intracellular DNA sensors in immunity.2008

    • Author(s)
      F.Takeshita, K.J.Ishii.
    • Journal Title

      Curr Opin Immunol 20

      Pages: 383-388

    • Related Report
      2010 Final Research Report
  • [Journal Article] Molecular and cellular mechanisms of DNA vaccines2008

    • Author(s)
      Coban C, Koyama S, Takeshita F, Akira S, and Ishii KJ.
    • Journal Title

      Human Vaccine 4

      Pages: 453-456

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intracellular DNA sensors in immunity2008

    • Author(s)
      Takeshita F* and Ishii KJ.
    • Journal Title

      Current Opinion in Immunology 20

      Pages: 383-388

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] NLRP4 negatively regulates autophagic process through an association with Beclin1.2010

    • Author(s)
      Nao Jounai
    • Organizer
      The 16^<th> Takeda Science Foundation Symposium on Bioscience "Casting light on life"
    • Place of Presentation
      Sheraton Miyako Hotel東京
    • Year and Date
      2010-12-01
    • Related Report
      2010 Annual Research Report
  • [Presentation] A signaling polypeptide derived from an innate immune adaptor molecule can be harnessed as a new class of vaccine2009

    • Author(s)
      Kobiyama K, Ishii KJ, Takeshita F
    • Organizer
      Keystone Symposia on Molecular and Cellular Biology
    • Place of Presentation
      カナダ、バンプ
    • Year and Date
      2009-03-29
    • Related Report
      2008 Annual Research Report
  • [Presentation] A signaling polypeptide derived from an innate immune adaptor molecule can be harnessed as a new class of vaccine adjuvant.2009

    • Author(s)
      Takeshita F, Kobiyama K.
    • Organizer
      International Workshop co-sponsored by Yokohama City University, FDA.
    • Place of Presentation
      Yokohama.
    • Year and Date
      2009-03-04
    • Related Report
      2010 Final Research Report
  • [Presentation] 自然免疫活性化機序の解明と応用.2009

    • Author(s)
      武下文彦
    • Organizer
      第8回プロテオーム医療創薬研究会.
    • Place of Presentation
      横浜.
    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] 染色体外ヒストンH2Bを介する二本鎖DNA認識機構の利用2009

    • Inventor(s)
      武下文彦、小檜山康司、吉田篤司
    • Industrial Property Rights Holder
      公立大学法人 横浜市立大学
    • Patent Publication Number
      2011-109982
    • Filing Date
      2009-11-27
    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] カスパーゼリクルートメントドメインを応用した新規リコンビナントタンパク及びその用途2009

    • Inventor(s)
      武下文彦、小檜山康司、奥田研爾
    • Industrial Property Rights Holder
      公立大学法人 横浜市立大学
    • Filing Date
      2009-08-12
    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] カスパーゼリクルートメントドメインを応用した新規リコンビナントタンパク及びその用途2008

    • Inventor(s)
      武下文彦, 小檜山康司,奥田研爾
    • Industrial Property Rights Holder
      横浜市立大学
    • Filing Date
      2008-08-29
    • Related Report
      2008 Annual Research Report

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Published: 2008-04-01   Modified: 2018-03-28  

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