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

2009 Fiscal Year Final Research Report

• Project/Area Number: 18200032
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Biomedical engineering/Biological material science
• Research Institution: Hokkaido 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)
• Project Period (FY): 2006 – 2009
• 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

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.

Research Products

• [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
  • 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
  • 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
  • Peer Reviewed
• [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
  • 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
  • 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
  • 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
  • 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
  • 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 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
  • Peer Reviewed
• [Presentation] Multifunctional envelope-type nano device for non-viral gene delivery: Concept and application for nanomedicine (2009)
  • Author(s): H. Harashima
  • Organizer: Asian Federation for Pharmaceutical Sciences 2009
  • Place of Presentation: Hakata, Japan(invited)
  • Year and Date: 2009-10-17
• [Presentation] Multifunctional envelope-type Nano Device for in vivo systemic delivery of siRNA (2008)
  • Author(s): H. Harashima
  • Organizer: 68th International Congres of FIP
  • Place of Presentation: Basel, Switzerland(invited)
  • Year and Date: 2008-09-02
• [Presentation] Multifunctional envelope type nano device for non-viral gene delivery: Concept and application of Programmed Packaging (2007)
  • Author(s): H. Harashima
  • Organizer: 13th International Symposium on Recent Advances in Drug Delivery Systems
  • Place of Presentation: Salt Lake City, Utah, USA.(invited)
  • Year and Date: 20070226-20070228
• [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
• [Presentation] Controlled Intracellular Trafficking of Non-viral Vector (2007)
  • 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
• [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