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Development of multi-functional nanocarrier of siDNA and application for bone and joint diseases

Research Project

Project/Area Number 17390412
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Orthopaedic surgery
Research InstitutionThe University of Tokyo

Principal Investigator

ITAKA Keiji  The University of Tokyo, Graduate School of medicine, Lecturer (60292926)

Co-Investigator(Kenkyū-buntansha) CHUNG Ung-il  The University of Tokyo, Graduate School of Engineering, Professor (30345053)
KAWAGUCHI Hiroshi  The University of Tokyo, Hospital, Associate Professor (40282660)
NAKAMURA Kozo  The University of Tokyo, Hospital, Professor (60126133)
KATAOKA Kazunori  The University of Tokyo, Graduate School of Engineering, Professor (00130245)
Project Period (FY) 2005 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥16,490,000 (Direct Cost: ¥15,500,000、Indirect Cost: ¥990,000)
Fiscal Year 2007: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2006: ¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2005: ¥8,500,000 (Direct Cost: ¥8,500,000)
KeywordssiRNA / delivery system / nanocarrier / bone and joint disease / nanotechnology / polyplex micelle
Research Abstract

In this project, we developed the nanocarriers containing siRNA and analyzed the biological functions.
1. Molucular design of nanocarriers The nanocarriers were composed of siRNA (or siRNA conjugate) and cationic polymers. The formation of nanocarriers with narrow distribution was confirmed.
2. Growth inhibition of cultured cells on the spheroid culture system After applying RecQL1 siRNA using this nanocarrier, the growth of spheroid-shaped cells was effectively inhibited after a week of application. This effect was observed in a low concentration, indicating the stability of nanocarriers in the physiological condition, smooth penetration inside the spheroids, and facilitated uptake by the receptor-targeting ligands.
3. Evaluation of biocompatibility By the evaluation of cytotoxicity and biocompatibility using cultured cells, this nanocarrier was revealed to have minimal cytotoxicity. In addition, the expressions of house-keeping genes were not affected by the nanocarrier, indicating the excellent biocompatibility.
4. In vivo bone regeneration This nanocarrier was revealed to have good capacity for inducing cell differentiation, due to the high transfection efficiency, excellent biocompatibility and a sustained manner of gene expression. By applying this nanocarrier to the bone-defect model of mice, the better bone regeneration was induced compared to that by the adenoviral vector. We are planning to apply the siRNA nanocarriers to the in vivo studies with modifications such as installation of disulfide bonds into the carriers.

Report

(4 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • 2005 Annual Research Report
  • Research Products

    (51 results)

All 2008 2007 2006 2005

All Journal Article (31 results) (of which Peer Reviewed: 15 results) Presentation (12 results) Book (5 results) Patent(Industrial Property Rights) (3 results)

  • [Journal Article] PEG-Detachable Polyplex Micelles Based on Disulfide-Linked Block Catiomers as Bioresponsive Nonviral Gene Vectors2008

    • Author(s)
      Takae S, Itaka K, et a1
    • Journal Title

      J. Am Chem Soc 130

      Pages: 6001-6009

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] PEG-Detachable Polyplex Micelles Based on Disulfide-Linked Block Catiomers as Bioresponsive Nonviral Gene Vectors2008

    • Author(s)
      Takae S, Itaka K, et. al.
    • Journal Title

      J Am Chem Soc. 130(18)

      Pages: 6001-6009

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] PEG-Detachable Polyplex Micelles Based on Disulfide-Linked Block Catiomersas Bioresponsive Non-Viral Gene Vectors2008

    • Author(s)
      Takae S, Itaka K, et. al.
    • Journal Title

      J Am Chem Soc 130

      Pages: 6001-6009

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] pH-Responsive PEGylated nanogels as targetable and low invasive endosomolytic agents to induce the enhanced transfection efficiency of nonviral gene vectors2007

    • Author(s)
      Oishi M, Itaka K, et. al.
    • Journal Title

      Colloid Polym Sci 285

      Pages: 1055-1060

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Enhanced Growth Inhibition of Hepatic Multicellular Tumor Spheroids by Lactosylated Poly (ethylene glycol)-siRNA Conjugate Formulated in PEGylated Polyplexes2007

    • Author(s)
      Oishi M, Itaka K, et. al.
    • Journal Title

      ChemMedChem 2

      Pages: 1290-1297

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] A novel osteogenic helioxanthin-derivative acts in a BMP-dependent manner2007

    • Author(s)
      Ohba S, Itaka K, et. al.
    • Journal Title

      Biochem Biophys Res Commun 357

      Pages: 854-860

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Identification and characterization of the human SOX6 promoter2007

    • Author(s)
      Ikeda T, Itaka K, et. al.
    • Journal Title

      Biochem Biophys Res Commun 357

      Pages: 383-390

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Bone regeneration by regulated in vivo gene transfer using biocompatible polyplex nanomicelles.2007

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

      Mol Ther 15

      Pages: 1655-1662

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Gene delivery with biocompatible cationic polymer:Pharmacogenomic analysis on cell bioactivity2007

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

      Biomaterials. 28

      Pages: 5169-5175

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Enhanced Growth Inhibition of Hepatic Multicellular Tumor Spheroids by Lactosylated Poly(ethylene glycol)-siRNA Conjugate Formulated in PEGylated Polyplexes2007

    • Author(s)
      Oishi M, Itaka K, et. al.
    • Journal Title

      Chem Med Chem 2(9)

      Pages: 1290-1297

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] A novel osteogenic helioxanthin-derivative acts in a BMP-dependent manner2007

    • Author(s)
      Ohba S, Itaka K, et. al.
    • Journal Title

      Biochem Biophys Res Commun. 15 357(4)

      Pages: 854-860

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Identification and characterization of the human SOX6 promoter2007

    • Author(s)
      Ikeda T, Itaka K, et. al.
    • Journal Title

      Biochem Biophys Res Commun 357(2)

      Pages: 383-390

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Bone regeneration by regulated in vivo gene transfer using biocompatibli polyplex nanomicelles2007

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

      Mol Ther 15(9)

      Pages: 1655-1662

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Gene delivery with biocompatible cationic polymer : Pharmacogenomic analysis on cell bioactivity2007

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

      Biomaterials 28(34)

      Pages: 5169-5175

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Nano Bioengineering (Editor; Kazunori Kataoka) Chapter 2(1)2007

    • Author(s)
      Itaka K
    • Journal Title

      Kyorin Tosho

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] pH-Responsive PEGylated nanogels as targetable and low invasive endosomolytic agents to induce the enhanced transfection effciency of nonviral gene vectors2007

    • Author(s)
      Oishi M, Itaka K, et. al.
    • Journal Title

      Colloid Polym Sci 285

      Pages: 1055-1060

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Enhanced Growth Inhibition of Hepatic Multicellular Tumor Spheroids by Lactosylated Poly(ethvlene glvcol)-siRNA Coniugate Formulated in PEGylated Polyplexes2007

    • Author(s)
      Oishi M, Itaka K, et. al.
    • Journal Title

      Chem Med Chem 10

      Pages: 1290-1297

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Bone regeneration by regulated in vivo gene transfer using biocompatible polyplex nanomice2007

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

      Mol Ther 15

      Pages: 1655-1662

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene delivery with biocompatible cationic polymer:Pharmacogenomic analysis on cell bioac2007

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

      Biomaterials 28

      Pages: 5169-5175

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] pH-Responsive PEGylated nanogels as targetable and low invasive endosomolytic agents to induce the enhanced transfection efficiency of nonviral gene vectors.2007

    • Author(s)
      Motoi Oishi, Keiji Itaka, et al.
    • Journal Title

      Colloid and Polymer Science (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A novel osteogenic helioxanthin-derivative acts in a BMP-dependent manner2007

    • Author(s)
      Shinsuke Ohba, Keiji Itaka, et al.
    • Journal Title

      BBRC (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Bone regeneration by regulated in vivo gene transfer using biocompatible polyplex nanomicelles2007

    • Author(s)
      Keiji Itraka, Kazunori Kataoka, et al.
    • Journal Title

      Molecular Therapy (in press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] A PEG-Based Biocompatible Block Catiomer with High Buffering Capacity for the Construction of Polyplex Micelles Showing Efficient Gene Transfer toward Primary Cells.2006

    • Author(s)
      Kanayama N, Itaka K, et. al.
    • Journal Title

      Chem Med Chem 1

      Pages: 439-444

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] The State of the Art of Nanobioscience in Japan2006

    • Author(s)
      Ueno S, Itaka K, et. al.
    • Journal Title

      IEEE Trans. NanoBiosci 5

      Pages: 54-65

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] A PEG-Based Biocompatible Block Catiomer with High Buffering Capacity for the Construction of Polyplex Micelles Showing Efficient Gen Transfer toward Primary Cells2006

    • Author(s)
      Kanayama N, Itaka K, et. al.
    • Journal Title

      Chem Med Chem 1(4)

      Pages: 439-444

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] The State of the Art of Nanobioscience in Japan2006

    • Author(s)
      Ueno S, Itaka K, et. al.
    • Journal Title

      IEEE Trans. NanoBiosci 5(1)

      Pages: 54-65

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] PEG-based biocompatible block catiomer with high-buffering capacity for the construction of polyplex micells showing efficient gene transfer toward primary cells.2006

    • Author(s)
      N.Kanayama, K.Itaka, et al.
    • Journal Title

      ChemMedChem (in press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] The State of the Art of Nanobioscience in Japan2006

    • Author(s)
      S.Ueno, K.Itaka et al.
    • Journal Title

      IEEE Trans Nanobiosci. 5(1)

      Pages: 54-65

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Light-induced gene transfer from packaged DNA enveloped in a dendrimeric photosensitizer2005

    • Author(s)
      Nishiyama N, Itaka K, et. al.
    • Journal Title

      Nat Mater 4

      Pages: 934-941

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Light-induced gene transfer from packaged DNA enveloped in a dendrimeric photosensitizer2005

    • Author(s)
      Nishiyama N, Itaka K, et. al.
    • Journal Title

      Nat Mater 4(12)

      Pages: 934-941

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Light-induced gene transfer from packaged DNA enveloped in a dendrimeric photosensitizer2005

    • Author(s)
      N.Nishiyama, K.Itaka, et al.
    • Journal Title

      Nat. Mater. 4(12)

      Pages: 934-941

    • Related Report
      2005 Annual Research Report
  • [Presentation] Supra-molecular Assembly of Block Copolymers as Smart Nanocarriers for Gene and Drug Delivery2008

    • Author(s)
      Itaka K, et. al.
    • Organizer
      Materials Research Society (MRS) 2008 Spring Meeting
    • Place of Presentation
      San Francisco, CA, U.S.A.
    • Year and Date
      2008-03-25
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Supra-molecular Assembly of Block Copolymers as Smart Nanocarriers for Gene and Drug Delivery2008

    • Author(s)
      Keiji Itaka
    • Organizer
      Materials Research Society (MRS) 2008 Spring Meeting
    • Place of Presentation
      San Francisco, CA, USA
    • Year and Date
      2008-03-25
    • Related Report
      2007 Annual Research Report
  • [Presentation] ナノミセル遺伝子デリバリーの再生医療への応用2007

    • Author(s)
      位高 啓史
    • Organizer
      第29回日本バイオマテリアル学会大会
    • Place of Presentation
      大阪
    • Year and Date
      2007-11-26
    • Related Report
      2007 Annual Research Report
  • [Presentation] ナノミセル型遺伝子キャリアの再生医療への応用と機能解析2007

    • Author(s)
      位高 啓史
    • Organizer
      第22回日本整形外科学会基礎学術集会
    • Place of Presentation
      浜松
    • Year and Date
      2007-10-26
    • Related Report
      2007 Annual Research Report
  • [Presentation] In vivo bone regeneration without cell transplantation using supramolecular nanocarrier for gene delivery2007

    • Author(s)
      Keiji Itaka
    • Organizer
      第13回日本遺伝子治療学会
    • Place of Presentation
      名古屋
    • Year and Date
      2007-06-29
    • Related Report
      2007 Annual Research Report
  • [Presentation] Pharmacogenomic analysis of non-viral gene transfer:Feasibility of effective cell differentitation toward tissue engineering.2007

    • Author(s)
      Itaka K, et. al.
    • Organizer
      10th Annual Meeting of the American Society of Gene Therapy
    • Place of Presentation
      Seattle, WA. U.S.A.
    • Year and Date
      2007-06-02
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Pharmacogenomic analysis of non-viral gene transfer : Feasibility of effective cell differentiation toward tissue engineering2007

    • Author(s)
      Itaka K
    • Organizer
      10th Annual Meeting of the American Society of Gene Therapy
    • Place of Presentation
      Seattle, WA. U.S.A.
    • Year and Date
      2007-06-02
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Pharmacogenomic analysis of non-viral gene transfer: Feasibility of effective cell differentiation toward tissue engineering2007

    • Author(s)
      Keiji Itaka
    • Organizer
      10th Annual Meeting of the American Society of Gene Therapy
    • Place of Presentation
      Seattle, WA.U.S.A
    • Year and Date
      2007-05-31
    • Related Report
      2007 Annual Research Report
  • [Presentation] Biocompatible nanocarrier of plasmid DNA for bone regeneration2006

    • Author(s)
      Itaka K, et. al.
    • Organizer
      33rd Annual Meeting et Exposition of the Controlled Release Society
    • Place of Presentation
      Vienna, Austria
    • Year and Date
      2006-07-24
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Bone Regeneration by Osteogenic Gene Delivery without Cell Transplantation Using Supramolecular Nanocarrier2006

    • Author(s)
      Itaka K, et. al.
    • Organizer
      9th Annual Meeting of the American Society of Gene Therapy
    • Place of Presentation
      Baltimore, MD. U.S.A.
    • Year and Date
      2006-06-04
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Supramolecular nanocarrier for DNA facilitating regulated gene expression2005

    • Author(s)
      Itaka K, et. al.
    • Organizer
      The 6th International Conference on Intelligent Materials and Systems ICIM'05
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2005-07-05
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Supramolecular nanocarrier for DNA facilitating regulated gene expression2005

    • Author(s)
      Itaka K
    • Organizer
      The 6th International Conference on Intelligent Materials and Systems ICIM''05
    • Place of Presentation
      Tokyo, Japan
    • Year and Date
      2005-07-05
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 医療ナノテクノロジー -最先端医学とナノテクの融合-(監修:片岡 一則) 第II部第1章「ナノDDS」2007

    • Author(s)
      位高 啓史
    • Publisher
      杏林図書
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] 医療ナノテクノロジー-最先端医学とナノテクの融合-(監修:片岡 一則)第II部第1章「ナノDDS」(pp.86-108)2007

    • Author(s)
      位高 啓史
    • Total Pages
      227
    • Publisher
      杏林図書
    • Related Report
      2007 Annual Research Report
  • [Book] 高分子ナノキャリアを用いた遺伝子導入と再生医療への応用2007

    • Author(s)
      位高 啓史, 片岡 一則
    • Publisher
      メディカルレビュー(in press)
    • Related Report
      2006 Annual Research Report
  • [Book] 高分子ミセル型ナノキャリアによるDDSとティッシュエンジニアリングへの応用2006

    • Author(s)
      位たか 啓史, 片岡 一則
    • Publisher
      日本医学館(In press)
    • Related Report
      2005 Annual Research Report
  • [Book] ナノキャリアによる遺伝子・siRNAデリバリー2006

    • Author(s)
      位たか 啓史, 鄭 雄一, 片岡 一則
    • Total Pages
      400
    • Publisher
      日本臨牀社
    • Related Report
      2005 Annual Research Report
  • [Patent(Industrial Property Rights)] ポリカチオン荷電性ポリマー及び核酸のキャリヤーとしての使用2006

    • Inventor(s)
      位高 啓史 他7名
    • Industrial Property Rights Holder
      位高 啓史 他7名
    • Industrial Property Number
      2005-035233
    • Filing Date
      2006-02-28
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Patent(Industrial Property Rights)] ポリカチオン荷電性ポリマー及び核酸のキャリヤーとしての使用2005

    • Inventor(s)
      位たか 啓史他7名
    • Industrial Property Rights Holder
      東京大学
    • Industrial Property Number
      2005-035233
    • Filing Date
      2005-02-10
    • Related Report
      2005 Annual Research Report
  • [Patent(Industrial Property Rights)] ペプチドリガンドを有するブロック共重合体2005

    • Inventor(s)
      位たか 啓史他5名
    • Industrial Property Rights Holder
      東京大学
    • Industrial Property Number
      2005-054260
    • Filing Date
      2005-02-28
    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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