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Development of inflammatory cell-specific gene regulation system for gene therapeutic strategy

Research Project

Project/Area Number 20790042
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Physical pharmacy
Research InstitutionSt.Marianna University School of Medicine

Principal Investigator

ASAI Daisuke  St.Marianna University School of Medicine, 医学部, 助教 (10423485)

Project Period (FY) 2007 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2009: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2008: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
KeywordsIkappaBkinase / NF-kappaB / 遺伝子キャリアー / ドラッグデリバリー / 遺伝子治療 / IkappaB kinase
Research Abstract

We proposed a novel strategy called D-RECS (drug or gene delivery system responding to cellular signals) to convert an intracellular signal to transgene expression. Here we apply this concept to inflammatory cells by using Ix-B kinase as a signal molecule that triggers the gene expression. Candidate cationic substrates of Ix-B kinase beta (IKK.(3) were synthesized and their reactivity was investigated. The results of gel shift assay showed that the polyplex was disintegrated and free DNA was released in the presence of IKKf3. The polyplex comprising CMV-GFP plasmid DNA and the polymer expressed the transgene in living cells exposed to a pro-inflammatory stimulus. Our concept of cell-specific gene expression was proved to work in inflammatory cells. This method may provide a unique strategy for gene therapy exclusively in inflammatory cells.

Report

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

    (52 results)

All 2010 2009 2008 Other

All Journal Article (22 results) (of which Peer Reviewed: 21 results) Presentation (25 results) Book (1 results) Remarks (2 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Specific transgene expression in HIV-infected cells using protease-cleavable transcription regulator.2010

    • Author(s)
      Asai, D., Kuramoto, M., Shoji, Y., Kang, J.H., Kodama, B.K., Kawamura, K., Mori, T., Miyoshi, H., Niidome, T., Nakashima, H., Katayama, Y.
    • Journal Title

      J Control. Release 141

      Pages: 52-61

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Plasma protein kinase C (PKC)αas a biomarker for the diagnosis of cancers.2009

    • Author(s)
      Kang, J.H. *, Asai, D. *, Toita, R., Kitazaki, H., Katayama, Y. * (*: ontributed equally)
    • Journal Title

      Carcinogenesis 30

      Pages: 1927-1931

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inflammatory cell-specific gene regulation system responding to Iκ-B kinase beta activation.2009

    • Author(s)
      Asai, D., Tsuchiya, A., Kang, J.H., Kawamura, K., Oishi, J., Mori, T., Niidome, T., Shoji, Y., Nakashima, H., Katayama, Y.
    • Journal Title

      J. Gene Med. 11

      Pages: 624-632

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of transgene expression in tumor cells by exploiting endogenous intracellular signals.2009

    • Author(s)
      Asai, D., Kang, J.H., Toita, R., Tsuchiya, A., Niidome, T., Nakashima, H., Katayama, Y.
    • Journal Title

      Nanoscale Res. Lett. 4

      Pages: 229-233

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Cellular signal-specific peptide substrate is essential for the gene delivery system responding to cellular signals.2009

    • Author(s)
      Kang, J.H., Toita, R., Tomiyama, T., Oishi, J., Asai, D., Mori, T., Niidome, T., Katayama, Y.
    • Journal Title

      Bioorg. Med. Chem. Lett. 19

      Pages: 6082-6086

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Molecular mechanism of caspase-3-induced gene expression of polyplexes formed from polycations grafted with cationic substrate peptides.2009

    • Author(s)
      Kawamura, K., Kuramoto, M., Mori, T., Toita, R., Oishi, J., Sato, Y., Kang, J.H., Asai, D., Niidome, T., Katayama, Y.
    • Journal Title

      J. Biomater. Sci. Polym. Ed. 20

      Pages: 967-980

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Inflaminatory cell-specific gene regulation system responding to Iκ-Bkinase beta activation2009

    • Author(s)
      Asai, D., et al.
    • Journal Title

      J.Gene Med.

      Pages: 624-631

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Specific transgene expression in HIV-infected cells using protease-cleavable transcription regulator2009

    • Author(s)
      Asai, D., et al.
    • Journal Title

      J.Control. Release (印刷中)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Plasma protein kinase C(PKC)α as a biomarker for the diagnosis of cancers2009

    • Author(s)
      Kang, J.H., et al.
    • Journal Title

      Carcinogenesis (印刷中)

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Design of polymeric carriers for cancer-specific gene targeting: Utilization of abnormal protein kinase Ca activation in cancer cells.2008

    • Author(s)
      Kang, J.H., Asai, D., Kim, J.H., Mori, T., Toita, R., Tomiyama, T., Asami, Y., Oishi, J., Sato, Y., Niidome, T., Jun, B., Nakashima, H., Katayama, Y.
    • Journal Title

      J. Am. Chem. Soc. 130

      Pages: 14906-14907

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Direct measure of fluorescence intensity for efficient receptor-binding assay:Conjugates of ethinylcarboxyestradiol and 5(and 6)-carboxyfluorescein via a, w-diaminoalkanes as a tracer for estrogen receptor.2008

    • Author(s)
      Asai, D., Tokunaga, T., Kondo, K., Kawaguchi, T., Takayanagi, S., Shinmyozu, T., Nakai, M., Yakabe, Y., Shimohigashi, Y.
    • Journal Title

      J. Biochem. 143

      Pages: 781-792

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] A short peptide is a protein kinase C (PKC) a-specific substrate.2008

    • Author(s)
      Kang, J.H. *, Asai, D. *, Yamada, S. *, Toita, R., Oishi, J., Mori, T., Niidome, T., Katayama, Y. (*: contributed equally)
    • Journal Title

      Proteomics 8

      Pages: 2006-2011

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Drug delivery system based on responses to an HIV infectious signal.2008

    • Author(s)
      Asai, D., Kodama, B.K., Shoji, Y., Nakashima, H., Kawamura, K., Oishi, J., Kuramoto, M., Niidome, T., Katayama, Y.
    • Journal Title

      Med. Chem. 4

      Pages: 386-391

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Disordered cell-specific gene regulation system for suicide gene therapy.2008

    • Author(s)
      Asai, D., Nakashima, H.
    • Journal Title

      Jpn. J. Chemother 56

      Pages: 538-542

    • NAID

      10022594885

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Correlation between phosphorylation ratios by MALDI-TOF MS analysis and enzyme kinetics.2008

    • Author(s)
      Kang, J.H., Kuramoto, M., Tsuchiya, A., Toita, R., Asai, D., Sato, T.Y., Mori, T., Niidome, T., Katayama, Y.
    • Journal Title

      Eur J. Mass Spectrom. 14

      Pages: 261-265

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Design of Polymeric Carriers for Cancer- specific Gene Targeting : Util ization of Abnormal Activation of Protein Kinase Cα in Cancer Cells2008

    • Author(s)
      Kang JH, et.al.
    • Journal Title

      J. Am. Chem. Soc 130

      Pages: 14906-14907

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Regulation of Transgene Expression in Tumor Cells by Exploiting Int racellular Signals2008

    • Author(s)
      Asai D, et.al.
    • Journal Title

      Nanoscale Res. Lett 4

      Pages: 229-233

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Disordered Cell-specific Gene Regulation System for Suicide Gene Therapy2008

    • Author(s)
      Asai D, et.al.
    • Journal Title

      Jpn. J. Chemother 56

      Pages: 538-542

    • NAID

      10022594885

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Correlation Between Phosphorylation Ratios by MALDI-TOF MS Analysis and Enzyme Kinetics2008

    • Author(s)
      Kang JH, et.al.
    • Journal Title

      Eur J. Mass Spectrom 14

      Pages: 261-265

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hepatoma-targeted gene delivery using a tumor cell-specific gene regulation system combined with a human liver cell-specific bionanocapsule.

    • Author(s)
      Kang, J.H., Oishi, J., Kim, J.H., Ijuin, M., Toita, R., Jun, B., Asai, D., Mori, T., Niidome, T., Tanizawa, K., Kuroda, S., Katayama, Y.
    • Journal Title

      Nanomedicine (in press)

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Progress in current non-viral carriers for gene delivery.

    • Author(s)
      Shoji-Moskowitz, Y, Asai, D., Kodama, K., Katayama, Y., Nakashima, H.
    • Journal Title

      Frontiers in Medicinal Chemistry (in press)

    • Related Report
      2009 Final Research Report
  • [Journal Article] Molecular Mechanism of Caspase- 3- induced Gene Expression of Poly plexes Formed from Polycations Grafted with Cationic Substrate Peptides

    • Author(s)
      Kawamura K, et.al.
    • Journal Title

      J. Biomater. Sci. Polym. Ed (印刷中)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] 疾患細胞特異的な遺伝子発現制御法の開発-第2報2009

    • Author(s)
      浅井大輔、姜貞勲、三好洋、片山佳樹、中島秀喜
    • Organizer
      第65回神奈川県感染症医学会学術集会
    • Place of Presentation
      横浜
    • Year and Date
      2009-03-21
    • Related Report
      2009 Final Research Report
  • [Presentation] 疾患細胞特異的な遺伝子発現制御法の開発-第2報2009

    • Author(s)
      浅井大輔, ほか
    • Organizer
      第65回神奈川県感染症医学会
    • Place of Presentation
      横浜
    • Year and Date
      2009-03-21
    • Related Report
      2008 Annual Research Report
  • [Presentation] Inflammatory signal-sensing polymer responding to IK-B kinase beta act ivat ion.2009

    • Author(s)
      Asai, D., Tsuchiya, A., Kang, J.H., Niidome, T., Nakashima, H., Ka tayama, Y.
    • Organizer
      8th International Symposium on Front iers in Biomedical Polymers (FBPS2009)
    • Place of Presentation
      Mishima
    • Related Report
      2009 Final Research Report
  • [Presentation] Specific transgene expression in virus-infected cells by a virus protease-cleavable transcription suppressor.2009

    • Author(s)
      Asai, D., Kuramo to, M., Kang, J.H., Niidome, T., Miyoshi, H., Nakashima, H., Katayama, Y.
    • Organizer
      BIT Life Sciences' 2nd Annual Protein and Peptide Conference (PepCon-2009)
    • Place of Presentation
      Seoul, South Korea
    • Related Report
      2009 Final Research Report
  • [Presentation] Specific transgene expression in virus-infected cells by a virus protease-cleavable transcription suppressor2009

    • Author(s)
      Asai, D., et al.
    • Organizer
      BIT Life Sciences' 2^<nd> Annual Protein and Peptide Conference (PepCon-2009)
    • Place of Presentation
      South Korea
    • Related Report
      2009 Annual Research Report
  • [Presentation] Inflammatory signal-sensing polymer responding to Iκ-B kinase bet a achvation2009

    • Author(s)
      Asai, D., et al.
    • Organizer
      8^<th> International Symposium on Frontiers in Biomedical Polyxners (FBPS2009)
    • Place of Presentation
      Mishima
    • Related Report
      2009 Annual Research Report
  • [Presentation] PKCα-responsive gene regulator for cancer cell-specific imaging and therapy2009

    • Author(s)
      Katayama, Y., et al.
    • Organizer
      8^<th> International Symposium on Frontiers in Biomedical Polyxners (FBPS2009)
    • Place of Presentation
      Mishima
    • Related Report
      2009 Annual Research Report
  • [Presentation] HIVプロテアーゼ阻害能を示した低分子化合物2009

    • Author(s)
      金本大成, ほか
    • Organizer
      第57回日本化学療法学会総会
    • Place of Presentation
      Tokyo
    • Related Report
      2009 Annual Research Report
  • [Presentation] Granulicatella elegans由来のアルギニン水解酵素によるリンパ球増殖抑制2008

    • Author(s)
      金本大成, ほか
    • Organizer
      第64回神奈川感染症医学会
    • Place of Presentation
      横浜
    • Year and Date
      2008-09-27
    • Related Report
      2008 Annual Research Report
  • [Presentation] 癌細胞特異的シグナル応答型遺伝子送達システム2008

    • Author(s)
      姜貞勲, ほか
    • Organizer
      遺伝子・デリバリー研究会第8回シンポジウム
    • Place of Presentation
      大阪
    • Year and Date
      2008-05-09
    • Related Report
      2008 Annual Research Report
  • [Presentation] 抗ウィルス薬開発の新戦略-ウイルス感染細胞特異的な遺伝子発現制御法の創出2008

    • Author(s)
      浅井大輔、三好洋、中島秀喜
    • Organizer
      第56回日本ウイルス学会学術集会
    • Place of Presentation
      岡山
    • Related Report
      2009 Final Research Report
  • [Presentation] Tumor intracellular signal-targeting by application of specific substrate peptide for protein kinasecc2008

    • Author(s)
      Asai, D., Knag, J.H., Toita, R., Tomiyama, T., Mori, T., Niidome, T., Nakashima, H., Katayama, Y.
    • Organizer
      17' Meeting of Methods in Protein Structure Analysis
    • Place of Presentation
      Sapporo
    • Related Report
      2009 Final Research Report
  • [Presentation] HIV感染シグナルに応答する遺伝子発現制御材料の開発2008

    • Author(s)
      浅井大輔、倉本政則、森健、新留琢郎、東海林洋子、片山佳樹、中島秀喜
    • Organizer
      第24回日本DDS学会学術集会
    • Place of Presentation
      東京
    • Related Report
      2009 Final Research Report 2008 Annual Research Report
  • [Presentation] 細菌由来のアルギニン水解酵素によるリンパ球増殖抑制2008

    • Author(s)
      金本大成, ほか
    • Organizer
      第82回日本感染症学会総会
    • Place of Presentation
      松江
    • Related Report
      2008 Annual Research Report
  • [Presentation] 人工遺伝子転写制御システムを用いる細胞内シグナルイメージング2008

    • Author(s)
      片山佳樹, ほか
    • Organizer
      日本ケミカルバイオロジー研究会第3回年会
    • Place of Presentation
      東京
    • Related Report
      2008 Annual Research Report
  • [Presentation] 癌細胞を標的とした細胞内シグナル応答型遺伝子送達システム2008

    • Author(s)
      姜貞勲, ほか
    • Organizer
      第17回化学とマイクロ・ナノシステム研究会
    • Place of Presentation
      福岡
    • Related Report
      2008 Annual Research Report
  • [Presentation] 細胞内シグナルを利用する標的疾患細胞特異的遺伝子送達2008

    • Author(s)
      片山佳樹, ほか
    • Organizer
      日本薬剤学会第23回年会
    • Place of Presentation
      札幌
    • Related Report
      2008 Annual Research Report
  • [Presentation] ウイルス感染細胞選択的な遺伝子発現制御システムの構築2008

    • Author(s)
      倉本政則, ほか
    • Organizer
      第57回高分子学会
    • Place of Presentation
      横浜
    • Related Report
      2008 Annual Research Report
  • [Presentation] A novel gene carrier responding to virus protease2008

    • Author(s)
      Kuramoto, M., et.al.
    • Organizer
      35^<th> Annual Meeting & Expression of the Controlled Release Society
    • Place of Presentation
      New York, USA
    • Related Report
      2008 Annual Research Report
  • [Presentation] Tumor intracellular signal- targeting by application of speci ficsubstrate peptide for protein kinase Cα2008

    • Author(s)
      Asai, D., et.al.
    • Organizer
      17^<th> Meeting of Methods in Protein Structure Analysis
    • Place of Presentation
      Sapporo
    • Related Report
      2008 Annual Research Report
  • [Presentation] 新規クロマチン機能モデル-遺伝子転写を制御する高分子2008

    • Author(s)
      片山佳樹, ほか
    • Organizer
      第57回高分子討論会
    • Place of Presentation
      大阪
    • Related Report
      2008 Annual Research Report
  • [Presentation] がん細胞内環境を認識して遺伝子発現制御を行う高分子-ペプチドコンジュゲート2008

    • Author(s)
      姜貞勲, ほか
    • Organizer
      第57回高分子討論会
    • Place of Presentation
      大阪
    • Related Report
      2008 Annual Research Report
  • [Presentation] 抗ウイルス薬開発の新戦略- ウイルス感染細胞特異的な遺伝子発現制御法の創出2008

    • Author(s)
      浅井大輔, ほか
    • Organizer
      第56回日本ウイルス学会
    • Place of Presentation
      岡山
    • Related Report
      2008 Annual Research Report
  • [Presentation] 細胞内シグナル応答型遺伝子キャリアーのソノポレーション法による高効率な細胞導入2008

    • Author(s)
      土谷享, ほか
    • Organizer
      日本バイオマテリアル学会シンポジウム2008
    • Place of Presentation
      東京
    • Related Report
      2008 Annual Research Report
  • [Presentation] 細胞内シグナル応答型遺伝子制御型キャリヤーの設計2008

    • Author(s)
      片山佳樹, ほか
    • Organizer
      日本バイオマテリアル学会シンポジウム2008
    • Place of Presentation
      東京
    • Related Report
      2008 Annual Research Report
  • [Book] 国際科学技術財團研究助成研究内容解説(疾患細胞選択的な遺伝子発現制御技術の創出と治療への応用(細胞と対話する技術の創出-薬物を病変細胞でだけ働かせる新しい考え方))2009

    • Author(s)
      浅井大輔
    • Related Report
      2009 Final Research Report
  • [Remarks] 研究室ホームページ(研究業績等)

    • URL

      http://www.marianna-u.ac.jp/microbiology/office/003347.html

    • Related Report
      2009 Final Research Report
  • [Remarks] 国際科学技術財団研究助成

    • URL

      http://www.japanprize.jp/subsidy_h20.html

    • Related Report
      2009 Final Research Report
  • [Patent(Industrial Property Rights)] Rho-キナーゼの新規基質ペプチド2009

    • Inventor(s)
      片山佳樹、姜貞勲、浅井大輔
    • Industrial Property Rights Holder
      片山佳樹、姜貞勲、浅井大輔
    • Industrial Property Number
      2009-211147
    • Filing Date
      2009
    • Acquisition Date
      2009
    • Related Report
      2009 Final Research Report
  • [Patent(Industrial Property Rights)] 蛍光リガンド及び化学物質のアンドロゲン受容体への結合強度測定方法2008

    • Inventor(s)
      下東康幸、中井誠、浅井大輔、矢可部芳州
    • Industrial Property Rights Holder
      下東康幸、中井誠、浅井大輔、矢可部芳州
    • Filing Date
      2008
    • Acquisition Date
      2008
    • Related Report
      2009 Final Research Report

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Published: 2008-04-01   Modified: 2016-04-21  

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