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Development of cationic histone deacetylase inhibitors as enhancer of gene transfection and expression

Research Project

Project/Area Number 21590131
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Drug development chemistry
Research InstitutionKansai University

Principal Investigator

NAGAOKA Yasuo  関西大学, 化学生命工学部, 教授 (90243039)

Co-Investigator(Kenkyū-buntansha) HATTORI Yoshiyuki  星薬科大学, 薬学部, 准教授 (90350222)
UESATO Shinichi  関西大学, 化学生命工学部, 教授 (50111969)
Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywordsリポフェクション / ヒストン脱アセチル化酵素阻害剤 / 非ウイルスベクター / 遺伝子発現 / HDAC / 遺伝子導入 / HDAC阻害剤 / ヒストン脱アセチル化酵素
Research Abstract

Lipofection is the most versatile transfection methods to transfect genes into mammalian cells, because of its safety and its handiness. However, the expression efficiency of the transfected genes with this method is much lower than that with viral vector. We therefore attempted to develop highly efficient enhancer for lipofection. According to this objective, we accomplished the development of lipofection enhancers which enhance the expression of genes up to 23 times more than that of control. Structure of the enhancer is based on histone deacetylase(HDAC) inhibitors, which increase acetylation level of histone in nucleus resulting in the enhancement of transcription efficiencies. HDAC inhibitors also inhibit a cytosolic isozyme of HDAC_s, HDAC6, to facilitate transportation of transfected genes to the nucleus. This may also contribute to the enhancement of the transfected gene expression.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (23 results)

All 2012 2011 2010 2009 Other

All Journal Article (9 results) (of which Peer Reviewed: 9 results) Presentation (9 results) Remarks (2 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] Anti-tumor activity of new orally bioavailable 2-amino-5-(thiophen-2-yl) benzamide-series histone deacetylase inhibitors, possessing an aqueous soluble functional group as a surface recognition domain2012

    • Author(s)
      Y. Hirata, M. Hirata, Y. Kawaratani, M. Shibano, M. Taniguchi, M. Yasuda, Y. Ohmomo, Y. Nagaoka, K. Baba, S. Uesato
    • Journal Title

      Bioorg. Med. Chem. Lett

      Volume: 22(5) Pages: 1926-1930

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Antitumor effect of liposomal histone deacetylase inhibitor-lipid conjugates in vitro2011

    • Author(s)
      Y. Hattori, Y. Nagaoka, M. Kubo, H. Yamasaku, Y. Ishii, S. Uesato, Y. Maitani
    • Journal Title

      Chem. Pharm. Bull

      Volume: 59(11) Pages: 1386-1392

    • NAID

      130001274814

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] New microtubule polymerization inhibitors comprising a nitrooxymethylphenyl group2011

    • Author(s)
      Y.Kawaratani, T.Harada, Y.Hirata, Y.Nagaoka, S.Uesato, 他5名
    • Journal Title

      Bioorg.Med.Chem.

      Volume: 19 Issue: 13 Pages: 3995-4003

    • DOI

      10.1016/j.bmc.2011.05.031

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A potent inhibitor of SIK2, 3,3',7-trihydroxy-4'-methoxyflavon (4'-O-methylfisetin), promotes melanogenesis in B16F10 melanoma cells2011

    • Author(s)
      A.Kumagai, N.Horike, Y.Satoh, H.Takemori, Y.Naeaoka, 他6名
    • Journal Title

      PLoS ONE

      Volume: 6 Issue: 10 Pages: 26148-26148

    • DOI

      10.1371/journal.pone.0026148

    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Antitumor Effect of Liposomal Histone Deacetylase Inhibitor-Lipid Conjugates in Vitro2011

    • Author(s)
      Y.Hattori, Y.Nagaoka, Shinichi Uesato, 他4名
    • Journal Title

      Chemical and Pharmaceutical Bulletin

      Volume: 59 Issue: 11 Pages: 1386-1392

    • DOI

      10.1248/cpb.59.1386

    • NAID

      130001274814

    • ISSN
      0009-2363, 1347-5223
    • Related Report
      2011 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Therapeutic Effect of Arctiin and Arctigenin in Immunocompetent and Immunocompromised Mice Infected with Influenza A Virus2010

    • Author(s)
      K.Hayashi, K.Narutaki, Y.Nagaoka, T.Hayashi, S.Uesato
    • Journal Title

      Biol.Pharm.Bull.

      Volume: 33 Pages: 1199-1205

    • NAID

      130000300287

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Molecular bases of cyclodextrin adapter interactions with engineered protein nanopores2010

    • Author(s)
      A.Banerjee, E.Mikhailova, S.Cheley, Li-Qun Gub, M.Montoyac, Y.Nagaoka, E.Gouaux, H.Bayley
    • Journal Title

      Proc.Natl.Acad.Sci.USA

      Volume: 107 Pages: 8165-8170

    • Related Report
      2010 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Histone Deacetylase Inhibitor Prodrugs in Nanoparticle Vector Enhanced Gene Expression in Human Cancer Cells Euro2009

    • Author(s)
      Y. Ishii, Y. Hattori, T. Yamada, S. Uesato, Y. Maitani, Y. Nagaoka
    • Journal Title

      J. Med. Chem

      Volume: 44(11) Pages: 4603-4610

    • Related Report
      2011 Final Research Report
    • Peer Reviewed
  • [Journal Article] Histone Deacetylase Inhibitor Prodrugs in Nanoparticle Vector Enhanced Gene Expression in Human Cancer Cells2009

    • Author(s)
      Y.Ishii, Y.Hattori, T.Yamada, S.Uesato, Y.Maitani, Y.Nagaoka
    • Journal Title

      Euro.J.Med.Chem. 44

      Pages: 4603-4610

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] ヒストン脱アセチル化酵素阻害剤とその誘導体のリポフェクションに及ぼす影響2012

    • Author(s)
      長岡康夫, 吉野宏美, 小林真理子, 置田裕子, 中野宏樹, 上里新一
    • Organizer
      日本薬学会第132年会
    • Place of Presentation
      北海道大学
    • Related Report
      2011 Annual Research Report 2011 Final Research Report
  • [Presentation] Histone Deacetylase Inhibitors as Lipofection Enhancer2011

    • Author(s)
      H.Yoshino, M.Kobayashi, H.Okita, H.Nakano, S.Uesato, Y.Nagaoka
    • Organizer
      8th AFMC International Medicinal Chemistry Symposium
    • Place of Presentation
      京王プラザホテル(東京)
    • Year and Date
      2011-11-29
    • Related Report
      2011 Annual Research Report
  • [Presentation] Histone Deacetylase Inhibitors as Lipofection Enhancer2011

    • Author(s)
      H. Yoshino, M. Kobayashi, H. Okita, H. Nakano, S. Uesato, Y. Nagaoka
    • Organizer
      8th AFMC International Medicinal Chemistry Symposium
    • Place of Presentation
      京王プラザホテル
    • Related Report
      2011 Final Research Report
  • [Presentation] 類型の異なるヒストン脱アセチル化酵素阻害剤がリポフェクション効率におよぼす影響2011

    • Author(s)
      吉野宏美、置田裕子、中野宏樹、服部喜之、米谷芳枝、上里新一、長岡康夫
    • Organizer
      日本薬学会131年会
    • Place of Presentation
      グランシップツインメッセ静岡
    • Related Report
      2011 Final Research Report
  • [Presentation] リポフェクション効率向上効果を有するプロドラッグ化ヒストン脱アセチル化酵素阻害剤2011

    • Author(s)
      置田裕子、中野宏樹、吉田耕平、吉野宏美、上里新一、服部喜之、米谷芳枝、長岡康夫
    • Organizer
      日本薬学会131年会
    • Place of Presentation
      グランシップツインメッセ静岡
    • Related Report
      2011 Final Research Report
  • [Presentation] Prodrugs of Histone Deacetylase Inhibitor K-182 Enhanced Expression of Genes Transfected with Cationic Cholesterol-Based Nanoparticle Vector2010

    • Author(s)
      H.Okita, Y.Ishii, S.Uesato, Y.Hattori, Y.Maitani, Y.Nagaoka
    • Organizer
      11th Tetrahedron Symposium
    • Place of Presentation
      北京大学(中国)
    • Year and Date
      2010-06-22
    • Related Report
      2010 Annual Research Report
  • [Presentation] Acyl Suberoylanilide Hydroxamic Acid as Lipofection Enhancer2010

    • Author(s)
      H. Nakano, S. Uesato, Y. Nagaoka
    • Organizer
      11th Tetrahedron Symposium
    • Place of Presentation
      北京大学
    • Related Report
      2011 Final Research Report
  • [Presentation] Prodrugs of Histone Deacetylase Inhibitor K-182 Enhanced Expression of Genes Transfected with Cationic Cholesterol-Based Nanoparticle Vector2010

    • Author(s)
      H. Okita, Y. Ishii, S. Uesato, Y. Hattori, Y. Maitani, Y. Nagaoka
    • Organizer
      11th Tetrahedron Symposium
    • Place of Presentation
      北京大学
    • Related Report
      2011 Final Research Report
  • [Presentation] 新規遺伝子発現増強剤DDTS-K-1822010

    • Author(s)
      中野宏樹、置田裕子、石井佑太、長岡康夫、上里新一、服部喜之、米谷芳枝
    • Organizer
      日本薬学会第130年会
    • Place of Presentation
      岡山大学
    • Related Report
      2011 Final Research Report 2009 Annual Research Report
  • [Remarks]

    • URL

      http://pharm.life-bio.kansai-u.ac.jp/

    • Related Report
      2011 Final Research Report
  • [Remarks]

    • URL

      http://pharm.life-bio.kansai-u.ac.jp/

    • Related Report
      2011 Annual Research Report
  • [Patent(Industrial Property Rights)] 遺伝子発現増強剤2012

    • Inventor(s)
      長岡康夫、上里新一
    • Industrial Property Rights Holder
      学校法人関西大学
    • Industrial Property Number
      2012-052395
    • Filing Date
      2012-03-09
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] メイラード反応阻害剤2012

    • Inventor(s)
      長岡康夫、河原秀久、山本秀樹、芝田隼次、小幡斉、上里新一
    • Industrial Property Rights Holder
      学校法人関西大学
    • Acquisition Date
      2012-01-06
    • Related Report
      2011 Final Research Report
  • [Patent(Industrial Property Rights)] 遺伝子導入剤2012

    • Inventor(s)
      長岡康夫, 上里新一
    • Industrial Property Rights Holder
      関西大学
    • Industrial Property Number
      2012-052395
    • Filing Date
      2012-03-09
    • Related Report
      2011 Annual Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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