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In vivo functional analysis of type 2 diabetes related new genes using liver siRNA delivery technique

Research Project

Project/Area Number 21800001
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeSingle-year Grants
Research Field Biomedical engineering/Biological material science
Research InstitutionHokkaido University

Principal Investigator

HAYASHI Yasuhiro  Hokkaido University, 大学院・薬学研究院, 特任助教 (30548178)

Project Period (FY) 2009 – 2010
Project Status Completed (Fiscal Year 2010)
Budget Amount *help
¥2,821,000 (Direct Cost: ¥2,170,000、Indirect Cost: ¥651,000)
Fiscal Year 2010: ¥1,261,000 (Direct Cost: ¥970,000、Indirect Cost: ¥291,000)
Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords肝臓 / siRNAデリバリー / in vivo 機能解析 / マイクロアレイ解析 / 2型糖尿病 / in vivo機能解析 / 遺伝子発現活性 / 細胞分離
Research Abstract

First, nucleic acid such as pDNA and siRNA delivery system to the liver was developed. This mission was achieved by optimizing the density of R8 peptide which has high ability to internalize into cell and GALA peptide as pH sensitive fusogenic peptide. Second, a new candidate gene which related the progression of type 2 diabetes was screened by DNA microarray analysis. Third, in vivo functional analysis of this new gene was performed using siRNA. When knocking down for this gene in the liver of type 2 diabetes model mice, significant reduction of both blood glucose level and body weight was observed. Thus, this new gene is promising therapeutic target for type 2 diabetes as well as obesity.

Report

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

    (22 results)

All 2011 2010 2009

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (17 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] DNA microarray analysis of whole blood cells and insulin-sensitive tissues reveals the usefulness of blood RNA profiling as a source of markers for predicting type 2 diabetes.2010

    • Author(s)
      Hayashi Y, Kajimoto K, Iida S, Sato Y, Mizufune S, Kaji N, Kamiya H, Baba H, Harashima H
    • Journal Title

      Biol.Pharm.Bull. 33(6)

      Pages: 1033-42

    • NAID

      130000247975

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Comparison between a multifunctional envelope-type nano device and lipoplex for delivery to the liver.2010

    • Author(s)
      Yamauchi J, Hayashi Y, Kajimoto K, Akita H, Harashima H
    • Journal Title

      Biol.Pharm.Bull. 33(5)

      Pages: 926-9

    • NAID

      130000248062

    • Related Report
      2010 Final Research Report
    • Peer Reviewed
  • [Journal Article] Comparison between a multifunctional envelope-type nano device and lipoplex for delivery to the liver2010

    • Author(s)
      Yamauchi J, Hayashi Y, et al.
    • Journal Title

      Biological & Pharmaceutical Bulletin 33(印刷中)

    • NAID

      130000248062

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DNA microarray analysis of whole blood cells and insulin-sensitive tissues reveals the usefulness of blood RNA profiling as a source of markers for predicting type 2 diabetes2010

    • Author(s)
      Hayashi Y, et al.
    • Journal Title

      Biological & Pharmaceutical Bulletin 33(印刷中)

    • NAID

      130000247975

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Presentation] R8ペプチドを用いた肝臓への遺伝子送達システムの構築2011

    • Author(s)
      林泰弘、水野諒一、Khalil Ikramy、原島秀吉
    • Organizer
      日本薬学会第131年会
    • Place of Presentation
      静岡
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] The usefulness of multifunctional envelope-type nano device for gene delivery to the liver2010

    • Author(s)
      J.Yamauchi, Y.Hayashi, K.Kajimoto, H.Akita, H.Harashima
    • Organizer
      The 8^<th> International Symposium for Future Drug Discovery and Medical Care.
    • Place of Presentation
      Sapporo, Japan
    • Related Report
      2010 Final Research Report
  • [Presentation] Analysis of Intracellular Trafficking of MPC-Coated Multifunctional Envelope-Type Nano Device (MPC-MEND) in Isolated Hepatocyte2010

    • Author(s)
      M.Ukawa, H.Akita, T.Masuda, Y.Hayashi, T.Konno, K.Ishihara, H.Harashima
    • Organizer
      The 8^<th> International Symposium for Future Drug Discovery and Medical Care.
    • Place of Presentation
      Sapporo, Japan
    • Related Report
      2010 Final Research Report
  • [Presentation] Modification of biocompatible polymers and endosomal escape device can go up liver gene expression and prevent immune response2010

    • Author(s)
      Y.Hayashi, J.Yamauchi, H.Akita, T.Masuda, M.Ukawa, T.Konno, K.Ishihara, H.Harashima
    • Organizer
      International liposome research days & lipids liposomes & membrane biophysic.
    • Place of Presentation
      Vancouver, Canada
    • Related Report
      2010 Final Research Report
  • [Presentation] Comparison between a multifunctional envelope-type nano device and lipoplex to the liver2010

    • Author(s)
      J.Yamauchi, Y.Hayashi, K.Kajimoto, H.Akita, H.Harashima
    • Organizer
      International liposome research days & lipids liposomes & membrane biophysic.
    • Place of Presentation
      Vancouver, Canada
    • Related Report
      2010 Final Research Report
  • [Presentation] マウス肝プライマリー細胞における多機能性エンベロープ型ナノ構造体(MEND)のMPCポリマー修飾による遺伝子発現活性上昇メカニズムの解明2010

    • Author(s)
      鵜川真実、秋田英万、増田智也、林泰弘、金野智浩、石原一彦、原島秀吉
    • Organizer
      第26回日本DDS学会
    • Place of Presentation
      大阪
    • Related Report
      2010 Final Research Report
  • [Presentation] ナノキャリアとLipoplexにおける肝臓への遺伝子デリバリーの比較2010

    • Author(s)
      山内順、林泰弘、梶本和昭、秋田英万、原島秀吉
    • Organizer
      遺伝子・デリバリー研究会 第10回シンポジウム
    • Place of Presentation
      札幌
    • Related Report
      2010 Final Research Report
  • [Presentation] 多機能性エンベロープ型ナノ構造体のMPCポリマー修飾による肝実質細胞における遺伝子発現活性上昇のメカニズムの解明2010

    • Author(s)
      鵜川真実、秋田英万、増田智也、林泰弘、金野智浩、石原一彦、原島秀吉
    • Organizer
      遺伝子・デリバリー研究会 第10回シンポジウム
    • Place of Presentation
      札幌
    • Related Report
      2010 Final Research Report
  • [Presentation] Analysis of Intracellular Trafficking of MPC-Coated Multifunctional Envelope-Type Nano Device (MPC-MEND) in Isolated Hepatocyte2010

    • Author(s)
      M.Ukawa, H.Akita, T.Masuda, Y.Hayashi, T.Konno, K.Ishihara, H.Harashima
    • Organizer
      The 13^<th> Annual Meeting of the American Society of Gene and Cell Therapy
    • Place of Presentation
      Washington, DC, USA
    • Related Report
      2010 Final Research Report
  • [Presentation] 肝臓への遺伝子デリバリーにおけるナノキャリアとLipoplexの比較2010

    • Author(s)
      山内順、林泰弘、梶本和昭、秋田英万、原島秀吉
    • Organizer
      日本薬剤学会第25年会
    • Place of Presentation
      徳島
    • Related Report
      2010 Final Research Report
  • [Presentation] MPCポリマー修飾GALA-MENDによる肝臓での遺伝子発現上昇と免疫応答の軽減2010

    • Author(s)
      林泰弘、山内順、秋田英万、増田智也、鵜川真実、金野智浩、石原一彦、原島秀吉
    • Organizer
      日本薬剤学会第25年会
    • Place of Presentation
      徳島
    • Related Report
      2010 Annual Research Report 2010 Final Research Report
  • [Presentation] 肝臓への遺伝子導入における多機能性エンベロープ型ナノ構造体の有用性の検証2010

    • Author(s)
      山内順、林泰弘、梶本和昭、秋田英万、原島秀吉
    • Organizer
      第134回薬学会北海道支部例会
    • Place of Presentation
      札幌
    • Related Report
      2010 Final Research Report
  • [Presentation] 多機能性エンベロープ型ナノ構造体のMPCポリマー修飾による遺伝子発現活性上昇機構の解明2010

    • Author(s)
      鵜川真実、秋田英万、増田智也、林泰弘、金野智浩、石原一彦、原島秀吉
    • Organizer
      第134回薬学会北海道支部例会
    • Place of Presentation
      札幌
    • Related Report
      2010 Final Research Report
  • [Presentation] 多機能性エンベロープ型ナノ構造体のMPCポリマー修飾による遺伝子発現活性上昇メカニズムの解明2010

    • Author(s)
      鵜川真実、秋田英万、増田智也、林泰弘、金野智浩、石原一彦、原島秀吉
    • Organizer
      第130回日本薬学会
    • Place of Presentation
      岡山
    • Related Report
      2010 Final Research Report
  • [Presentation] Modification of biocompatible polymers and endosomal escape device can go up liver gene expression and prevent immune response2010

    • Author(s)
      林泰弘
    • Organizer
      International liposome research days & lipids lipo somes & membrane biophysic
    • Place of Presentation
      Vancouver (Canda)
    • Related Report
      2010 Annual Research Report
  • [Presentation] 2型糖尿病の発症を予測するマーカーとしての白血球遺伝子発現プロファイルの有用性の検証2009

    • Author(s)
      林泰弘、梶本和昭、飯田慎也、加地範匡、高崎一朗、田渕圭章、紙谷浩之、馬場嘉信、原島秀吉
    • Organizer
      第52回日本糖尿病学会年次学術集会
    • Place of Presentation
      大阪
    • Year and Date
      2009-05-24
    • Related Report
      2010 Final Research Report
  • [Presentation] DNAマイクロアレイ解析による2型糖尿病遺伝子治療を可能とする新規標的遺伝子の探索2009

    • Author(s)
      高橋恭平、林泰弘、梶本和昭、飯田慎也、加地範匡、紙谷浩之、馬場嘉信、原島秀吉
    • Organizer
      日本薬剤学会第24年会
    • Place of Presentation
      静岡
    • Related Report
      2010 Final Research Report
  • [Patent(Industrial Property Rights)] 2型糖尿病診断剤2009

    • Inventor(s)
      原島秀吉、林泰弘、紙谷浩之、梶本和昭、馬場嘉信、加地範匡
    • Industrial Property Rights Holder
      国立大学法人北海道大学、国立大学法人名古屋大学
    • Industrial Property Number
      2009-125826
    • Filing Date
      2009-04-28
    • Related Report
      2010 Final Research Report

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

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