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Developping of the genetherapy for Fabry's disesase mouse using the newly designed peptide vector

Research Project

Project/Area Number 23590649
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Applied pharmacology
Research InstitutionJikei University School of Medicine

Principal Investigator

IWAMOTO Takeo  東京慈恵会医科大学, 医学部, 准教授 (90568891)

Research Collaborator KOBAYASHI Hiroshi  
TOMICH John M  
Project Period (FY) 2011-04-28 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords合成ペプチド / 新規ベクター / ファブリー病 / 遺伝子治療
Outline of Final Research Achievements

We designed a new class of branched amphiphilic peptide capsules(BAPC) that self-assemble into extremely stable nanospheres.BAPC mixed with gene were delivered to cells without cytotoxicity. But transfections were not enough high to apply gene therapy for mice.We investigated the biophysical properties and transfection efficiency for BAPC form peptiplexes with DNA. We found that, in the presence of double stranded plasmid DNA,BAPC are unable to form.Instead depending of the peptide/DNA ratios,the peptides either coat the plasmid surface forming nanofibers (high peptide to DNA ratio) or condense the plasmid into nanometer-sized compacted structures (low peptide to DNA ratios). Different gene delivery efficiencies are observed for the two types of assemblies.The compacted structures display much higher transfection in HeLa cells.This level of transfection is greater than that observed for a lipid-based reagent when the total number of viable transfected cells is taken into account.

Report

(5 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • 2012 Research-status Report
  • 2011 Research-status Report
  • Research Products

    (4 results)

All 2015 2014 2013 2012

All Journal Article (4 results) (of which Peer Reviewed: 4 results,  Acknowledgement Compliant: 1 results)

  • [Journal Article] Branched Amphiphilic Cationic Oligopeptides Form Peptiplexes with DNA: A Study of Their Biophysical Properties and Transfection Efficiency2015

    • Author(s)
      L. Adriana Avila, Luana R. M. M. Aps, Pinakin Sukthankar, Nicoleta Ploscariu, Sushanth Gudlur, Ladislav Šimo, Robert Szoszkiewicz, Yoonseong Park, Stella Y. Lee , Takeo Iwamoto, Luis C. S. Ferreira, John M. Tomich
    • Journal Title

      Molecular Pharmaceutics

      Volume: 12 Issue: 3 Pages: 706-715

    • DOI

      10.1021/mp500524s

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Branched amphiphilic peptide capsules: Cellular uptake and retention of encapsulated solutes.2014

    • Author(s)
      P. Sukthankar, LA. Avila, S. K. Whitaker, T. Iwamoto, A. Morgenstern, C. Apostolidis, K Liu, R. P. Hanzlik, E. Dadachova, J. M. Tomich
    • Journal Title

      Biochimica Et Biophysica Acta

      Volume: 1838 Issue: 9 Pages: 2296-2305

    • DOI

      10.1016/j.bbamem.2014.02.005

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Branched oligopeptides form nanocapsules with lipid vesicle characteristics.2013

    • Author(s)
      Sukthankar P, Gudlur S, Avila LA, Whitaker SK, Katz BB, Hiromasa Y, Gao J, Thapa P, Moore D, Iwamoto T, Chen J, Tomich JM.
    • Journal Title

      Langmuir

      Volume: 29 Pages: 14648-54

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Peptide Nanovesicles Formed by the Self-Assembly of Branched Amphiphilic Peptides2012

    • Author(s)
      Sushanth Gudlur, Pinakin Sukthankar, Jian Gao, L.Adriana Avila, Yasuaki Hiromasa, Jianhan Chen, Takeo Iwamoto, John M. Tomich
    • Journal Title

      PLOS ONE

      Volume: 7 Pages: 1-11

    • Related Report
      2012 Research-status Report
    • Peer Reviewed

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Published: 2011-08-05   Modified: 2019-07-29  

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