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Development of in vivo gene delivery system for siRNA and genome wide screening of type-two diabetes related genes in mice and rats

Research Project

Project/Area Number 18200032
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomedical engineering/Biological material science
Research InstitutionHokkaido University

Principal Investigator

HARASHIMA Hideyoshi  Hokkaido University, 大学院・薬学研究院, 教授 (00183567)

Co-Investigator(Kenkyū-buntansha) KAMIYA Hiroyuki  北海道大学, 大学院・薬学研究院, 准教授 (10204629)
YAMADA Yuma  北海道大学, 大学院・薬学研究院, 助教 (60451431)
BABA Yoshinobu  名古屋大学, 大学院・工学研究科, 教授 (30183916)
秋田 英万  北海道大学, 大学院・薬学研究院, 助教 (80344472)
小暮 健太朗  京都薬科大学, 薬学部, 教授 (70262540)
中谷 明弘  東京大学, 新領域創成科学研究科, 助教授 (60301149)
Project Period (FY) 2006 – 2009
Project Status Completed (Fiscal Year 2009)
Budget Amount *help
¥47,840,000 (Direct Cost: ¥36,800,000、Indirect Cost: ¥11,040,000)
Fiscal Year 2009: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Fiscal Year 2008: ¥10,010,000 (Direct Cost: ¥7,700,000、Indirect Cost: ¥2,310,000)
Fiscal Year 2007: ¥11,830,000 (Direct Cost: ¥9,100,000、Indirect Cost: ¥2,730,000)
Fiscal Year 2006: ¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Keywords遺伝子デリバリー / エンドサイトーシス / トランスサイトーシス / 多機能性エンベロープ型ナノ構造体 / 血管透過 / 2型糖尿病 / siRNA / 網羅的解析 / 遺伝子診断 / 遺伝子デリバリーシステム / GALA / IRO / ハイドロダイナミクス法 / カベオラ / R8-NEND
Research Abstract

We performed genome-wide screening of type-2 diabetes related genes which can be detectable in blood cells before disease state or after disease occurred. In parallel, we succeeded in developing in vivo gene delivery system for liver..In addition, we constructed an original assay system for nano carriers to evaluate transcytosis of endothelial cells and finally succeeded in finding a selective ligand for transcytosis of nano carriers.

Report

(6 results)
  • 2009 Annual Research Report   Final Research Report ( PDF )
  • 2008 Annual Research Report   Self-evaluation Report ( PDF )
  • 2007 Annual Research Report
  • 2006 Annual Research Report
  • Research Products

    (50 results)

All 2009 2008 2007 2006 Other

All Journal Article (27 results) (of which Peer Reviewed: 21 results) Presentation (12 results) Book (2 results) Patent(Industrial Property Rights) (9 results)

  • [Journal Article] Envelope-type lipid nanoparticles incorporating a short PEG-lipid conjugate for improved control of intracellular trafficking and transgene transcription.2009

    • Author(s)
      Masuda T, Akita H, Niikura K, Nishio T, Ukawa M, Enoto K, Danev R, Nagayama K, Ijiro K, Harashima H.
    • Journal Title

      Biomaterials 30(27)

      Pages: 4806-14

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced gene expression by a novel stearylated INF7 peptide derivative through fusion independent endosomal escape.2009

    • Author(s)
      El-Sayed A, Masuda T, Khalil I, Akita H, Harashima H.
    • Journal Title

      J Control Release. 138(2)

      Pages: 160-7

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Multi-layered nano particles for penetrating the endosome and nuclear membrane via a step-wise membrane fusion process.2009

    • Author(s)
      H. Akita, A. Kudo, A. Minoura, M. Yamaguchi, I. A Khalil, R. Moriguchi, T. Masuda, R. Danev, K. Nagayama, K. Kogure, H. Harashima
    • Journal Title

      Biomaterials 30(15)

      Pages: 2940-9

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Multi-layered nano particles for penetrating the endosome and nuclear membrane via a step-wise membrane fusion process.2009

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

      Biomaterials 30(15)

      Pages: 2940-9

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced gene expression by a novel stearylated INF7 peptide derivative through fusion independent endosomal escape.2009

    • Author(s)
      El-Sayed A, et al.
    • Journal Title

      J.Cont. Rel. 138(2)

      Pages: 160-7

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Envelope-type lipid nanoparticles incorporating a short PEG-lipid conjugate for improved control of intracellular trafficking and transgene transcription.2009

    • Author(s)
      Masuda T, et al.
    • Journal Title

      Biomaterials 30(27)

      Pages: 4806-14

    • Related Report
      2009 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Multi-layered nano particles for penetrating the endosome and nuclear membrane via a step-wise membrane fusion process2009

    • Author(s)
      H. Akita, A. Kudo, A. Minoura, M. Yamaguchi, I. A. Khalil, R. Moriguchi, T. Masuda, R. Danev, K. Nagayama, K. Kogure and H. Harashima.
    • Journal Title

      Biomaterials 30(15)

      Pages: 2940-9

    • Related Report
      2008 Self-evaluation Report
  • [Journal Article] Octaarginine-and octalysine-modified nanoparticles have different modes of endosomal escape.2008

    • Author(s)
      A. El-Sayed, IA. Khalil, K. Kogure, S. Futaki, H. Harashima
    • Journal Title

      J Biol Chem 283(34)

      Pages: 23450-61

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] An artificial virus-like nano carrier system: Enhanced endosomal escape of nano-particles via synergistic action of pH-sensitive fusogenic peptide derivatives.2008

    • Author(s)
      K. Sasaki, S. Chaki, Y. Nakamura, K. Kogure, H. Hamada, M. Ueno, S. Futaki, H. Harashima
    • Journal Title

      Anal Bioanal Chem 391(8)

      Pages: 2717-27

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel IRQ ligand-modified nano-carrier targeted to a unique pathway of caveolar endocytic pathway.2008

    • Author(s)
      D. Mudhakir, H. Akita, E. Tan, H. Harashima
    • Journal Title

      J Control Release 125(2)

      Pages: 164-173

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] A novel IRQ ligand-modified nano-carrier targeted to a unique pathway of caveolar endocytic pathway2008

    • Author(s)
      D. Mudhakir
    • Journal Title

      J Control Release 125(2)

      Pages: 164-173

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] An artificial virus-like nano carrier system : Enhanced endosomal escape of nano-particles via synergistic action of pH-sensitive fusogenic peptide derivatives2008

    • Author(s)
      K. Sasaki
    • Journal Title

      Anal Bioanal Chem. 391(8)

      Pages: 2717-27

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Octaarginine-and octalysine-modified nanoparticles have different modes of endosomal escape2008

    • Author(s)
      A. El-Sayed
    • Journal Title

      J Biol Chem. 283(34)

      Pages: 23450-61

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Development of lipid particles targeted via sugar-lipid conjugates as novel nuclear gene delivery system2008

    • Author(s)
      T. Masuda
    • Journal Title

      Biomaterials 29

      Pages: 709-723

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A novel IRQ ligand-modified nano-carrier targeted to a unique pathway of caveo lar endocytic pathway.2008

    • Author(s)
      D. Mudhakir
    • Journal Title

      J. Control Rel. 125(2)

      Pages: 164-173

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Octaarginine-modified multifunctional envelope-type nano device for siRNA.2007

    • Author(s)
      Y. Nakamura, K. Kogure, S. Futaki, H. Harashima
    • Journal Title

      J. Cont. Rel. 119(3)

      Pages: 360-7

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] DNA microarray analysis on type 2 diabetes-related genes co-regulated between white blood cells and liver of diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Biol.2007

    • Author(s)
      Y. Hayashi, S. Iida, Y. Sato, A. Nakaya, A. Sawada, N. Kaji, H. Kamiya, Y. Baba, H. Harashima
    • Journal Title

      Pharm. Bull 30(4)

      Pages: 763-771

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] Octaarginine-modified envelope-type nanoparticles for gene delivery. Gene Therapy nanoparticles for gene delivery2007

    • Author(s)
      I. A. Khalil, K. Kogure, S. Futaki, S. Hama, H. Akita, K. Kataoka, and H. Harashima
    • Journal Title

      Gene Therapy 14(8)

      Pages: 682-9

    • Related Report
      2008 Self-evaluation Report
  • [Journal Article] DNA microarray analysis on type 2 diabetes-related genes co-regulated between white blood cells and liver of diabetic Otsuka Long-Evans Tokushima Fatty(OLETF)rats.2007

    • Author(s)
      Y. Hayashi
    • Journal Title

      Biol. Pharm. Bull. 30(4)

      Pages: 763-771

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] DNA microarray analysis on type 2 diabetes-related genes co-regulated between white blood cells and liver of diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats.2007

    • Author(s)
      Y.Hayashi
    • Journal Title

      Biol. Pharm. Bull. (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Octaarginine-modified envelope-type nanoparticles for gene delivery.2007

    • Author(s)
      I.A.Khalil
    • Journal Title

      Gene Therapy (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Genome wide expression analysis of white blood cells and liver of pre-diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats using a cDNA microarray.2006

    • Author(s)
      S. Iida, Y. Sato, A. Nakaya, Y. Shinohara, Y. Hayashi, A. Sawada, H. Nagata, N. Kaji, H. Kamiya, Y. Baba, H. Harashima
    • Journal Title

      Biol. Pharm. Bull 29(12)

      Pages: 2451-9

    • NAID

      110006148670

    • Related Report
      2009 Final Research Report
    • Peer Reviewed
  • [Journal Article] High density of octaarginine stimulates macropincytosis leading to an efficient intracellular trafficking for gene expression2006

    • Author(s)
      1. I. A Khalil, K. Kogure, S. Futaki, and H. Harashima
    • Journal Title

      J. Biol. Chem. 281(6)

      Pages: 3544-51

    • Related Report
      2008 Self-evaluation Report
    • Peer Reviewed
  • [Journal Article] Genome wide expression analysis of white blood cells and liver of pre-diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats using a cDNA microarray2006

    • Author(s)
      S.Iida
    • Journal Title

      Biol. Pharm. Bull. 29・12

      Pages: 2451-2459

    • Related Report
      2006 Annual Research Report
  • [Journal Article] High density of octaarginine stimulates macropincytosis leading to an efficient intracellular trafficking for gene expression.2006

    • Author(s)
      I.A.Khalil
    • Journal Title

      J. Biol. Chem. 281・6

      Pages: 3544-3451

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Multi-layered nano particles for penetrating the endosome and nuclear membrane via a step-wise membrane fusion process

    • Author(s)
      H. Akita
    • Journal Title

      Biomaterials (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Novel Lipidated Sorbitol-based Molecular Transporters for Non-viral Gene Delivery

    • Author(s)
      T. Higashi
    • Journal Title

      1. J. Cont. Rel. (in press)

    • Related Report
      2008 Annual Research Report
    • Peer Reviewed
  • [Presentation] Multifunctional envelope-type nano device for non-viral gene delivery: Concept and application for nanomedicine2009

    • Author(s)
      H. Harashima
    • Organizer
      Asian Federation for Pharmaceutical Sciences 2009
    • Place of Presentation
      Hakata, Japan(invited)
    • Year and Date
      2009-10-17
    • Related Report
      2009 Final Research Report
  • [Presentation] Multifunctional envelope-type nano device for non-viral gene delivery : Concept and application for nanomedicine2009

    • Author(s)
      Hideyoshi Harashima
    • Organizer
      Asian Federation for Pharmaceutical Sciences 2009
    • Place of Presentation
      Centennial Hall Kyushu University, Fukuoka, Japan
    • Year and Date
      2009-10-17
    • Related Report
      2009 Annual Research Report
  • [Presentation] Multifunctional envelope-type nano device for non-viral gene delivery : Concept and application of programmed packaging2009

    • Author(s)
      Hideyoshi Harashima
    • Organizer
      The 8^<th> Cerebral Vascular Biology 2009
    • Place of Presentation
      Sendai Excel Hotel Tokyu, Sendai, Japan
    • Year and Date
      2009-07-01
    • Related Report
      2009 Annual Research Report
  • [Presentation] Multifunctional envelope-type Nano Device for in vivo systemic delivery of siRNA2008

    • Author(s)
      H. Harashima
    • Organizer
      68th International Congres of FIP
    • Place of Presentation
      Basel, Switzerland(invited)
    • Year and Date
      2008-09-02
    • Related Report
      2009 Final Research Report
  • [Presentation] 多機能性エンベロープ型ナノ構造体による人工遺伝子デリバリーシステムの創製2007

    • Author(s)
      原島秀吉
    • Organizer
      第23回日本DDS学会永井賞受賞講演
    • Place of Presentation
      熊本(invited)
    • Year and Date
      2007-06-15
    • Related Report
      2009 Final Research Report
  • [Presentation] Cellular uptake mechanism and intracellular trafficking study of the novel C152-peptide-modified liposomes(C152-Lip)2007

    • Author(s)
      ディッキームダキュル、秋田英万、タンエルダル、原島秀吉
    • Organizer
      第23回日本DDS学会
    • Place of Presentation
      熊本(熊本日航ホテル)
    • Year and Date
      2007-06-15
    • Related Report
      2007 Annual Research Report
  • [Presentation] A novel IRQ ligand modified nano-carrier mediated a unique caveolae targeting2007

    • Author(s)
      D. Mudhakir
    • Organizer
      The 10^<th> Annual Meeting of the American Society of Gene Therapy
    • Place of Presentation
      Boston, Massachusetts, USA.
    • Year and Date
      2007-06-01
    • Related Report
      2008 Self-evaluation Report
  • [Presentation] Controlled Intracellular Trafficking of Non-viral Vector2007

    • Author(s)
      H. Harashima
    • Organizer
      The 10th Annual Meeing of American Society of Gene Therapy: Education Session: Topical Review: Non-viral Vector esign and Efficacy
    • Place of Presentation
      Seatle, Washington, USA
    • Year and Date
      2007-05-30
    • Related Report
      2009 Final Research Report
  • [Presentation] 血液サンプルを用いた2型糖尿病の遺伝子診断システムの開発2007

    • Author(s)
      林泰弘、飯田慎也、中谷明弘、澤田章弘、加地範匡、紙谷浩之、馬場嘉信、原島秀吉
    • Organizer
      日本薬剤学会第22年会
    • Place of Presentation
      大宮(大宮ソニックシティ)
    • Year and Date
      2007-05-21
    • Related Report
      2007 Annual Research Report
  • [Presentation] 血管内皮細胞標的化ペプチド搭載リポソームの細胞内取り込み機構の解析2007

    • Author(s)
      秋田英万、ディッキー・ムダキュル、タン・エルダル、原島秀吉
    • Organizer
      日本薬剤学会第22年会
    • Place of Presentation
      大宮(大宮ソニックシティ)
    • Year and Date
      2007-05-21
    • Related Report
      2007 Annual Research Report
  • [Presentation] 多機能性エンベロープ型人工遺伝子デリバリーシステムの創製2007

    • Author(s)
      原島秀吉
    • Organizer
      日本薬学会第127年会(学術振興賞受賞講演)
    • Place of Presentation
      富山(invited)
    • Year and Date
      2007-03-29
    • Related Report
      2009 Final Research Report
  • [Presentation] Multifunctional envelope type nano device for non-viral gene delivery: Concept and application of Programmed Packaging2007

    • Author(s)
      H. Harashima
    • Organizer
      13th International Symposium on Recent Advances in Drug Delivery Systems
    • Place of Presentation
      Salt Lake City, Utah, USA.(invited)
    • Related Report
      2009 Final Research Report
  • [Book] 分子薬物動態学(第17章高分子・遺伝子の体内動態の制御(細胞内動態を中心に))2008

    • Author(s)
      秋田英万、原島秀吉
    • Total Pages
      19
    • Publisher
      南山堂
    • Related Report
      2008 Annual Research Report
  • [Book] Contrib Nephrol (Nonviral gene delivery)2008

    • Author(s)
      Akita H, Harashima H.
    • Total Pages
      19
    • Publisher
      KARGER
    • Related Report
      2008 Annual Research Report
  • [Patent(Industrial Property Rights)] 高分子化合物またはその複合体の細胞透過性評価装置及びその細胞透過性評価方法.2009

    • Inventor(s)
      原島秀吉, 秋田英万、藤原孝博、田畑泰彦
    • Industrial Property Rights Holder
      北海道大学、京都大学
    • Filing Date
      2009-12-03
    • Related Report
      2009 Annual Research Report
  • [Patent(Industrial Property Rights)] 脂質膜構造体に細胞透過能を付与するペプチドと結合した脂質を構成脂質として含む、細胞透過能を有する脂質膜構造体.2009

    • Inventor(s)
      原島秀吉, 秋田英万、藤原孝博
    • Industrial Property Rights Holder
      北海道大学
    • Filing Date
      2009-12-14
    • Related Report
      2009 Annual Research Report
  • [Patent(Industrial Property Rights)] 脂質膜構造体2009

    • Inventor(s)
      原島秀吉, 秋田英万、アイマンエルサイド、増田智也
    • Industrial Property Rights Holder
      北海道大学
    • Filing Date
      2009-03-23
    • Related Report
      2008 Annual Research Report
  • [Patent(Industrial Property Rights)] 2型糖尿病診断用キット2008

    • Inventor(s)
      原島秀吉、紙谷浩之、桑島正道
    • Industrial Property Rights Holder
      北海道大学
    • Acquisition Date
      2008-11-14
    • Related Report
      2008 Self-evaluation Report
  • [Patent(Industrial Property Rights)] オリゴアルキレングリコール修飾された脂質膜構造体2008

    • Inventor(s)
      原島秀吉,増田智也、秋田英万、居城邦治、新倉謙一、西尾崇
    • Industrial Property Rights Holder
      北海道大学
    • Filing Date
      2008-04-25
    • Related Report
      2008 Annual Research Report
  • [Patent(Industrial Property Rights)] 2型糖尿病の診断方法2008

    • Inventor(s)
      原島秀吉, 紙谷浩之, 桑島正道
    • Industrial Property Rights Holder
      北海道大学
    • Filing Date
      2008-08-11
    • Related Report
      2008 Annual Research Report
  • [Patent(Industrial Property Rights)] 脂質膜構造体2008

    • Inventor(s)
      原島秀吉,増田智也、秋田英万、石原一彦、金野智浩
    • Industrial Property Rights Holder
      北海道大学
    • Filing Date
      2008-12-12
    • Related Report
      2008 Annual Research Report
  • [Patent(Industrial Property Rights)] 2型糖尿病診断剤2007

    • Inventor(s)
      原島秀吉、飯田慎也、紙谷浩之、林泰弘、馬場嘉信
    • Industrial Property Rights Holder
      北海道大学, 名古屋大学
    • Industrial Property Number
      2007-072563
    • Filing Date
      2007-03-20
    • Related Report
      2008 Self-evaluation Report
  • [Patent(Industrial Property Rights)] 粒子を脂質膜で被覆する方法2006

    • Inventor(s)
      小暮健太朗、箕浦ありさ、原島秀吉
    • Industrial Property Rights Holder
      北海道大学
    • Filing Date
      2006-01-18
    • Related Report
      2008 Self-evaluation Report

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Published: 2006-04-01   Modified: 2016-04-21  

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