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Development of a chimeric navigator to capture and remove an etiologic agent in the blood

Research Project

Project/Area Number 15K16335
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Biomedical engineering/Biomaterial science and engineering
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

Kambe Yusuke  国立研究開発法人国立循環器病研究センター, 研究所, 流動研究員 (30747671)

Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2016: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2015: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Keywordsキメラタンパク / メタボリックスイッチング / DDS / DNCS / バイオマテリアル
Outline of Final Research Achievements

In the drug-navigated clearance system, a drug called “navigator” needs to be synthesized to switch the metabolic pathway of an etiologic agent. Here, dialysis-related amyloidosis was used as a model disease and its etiologic agent, beta 2-microglubulin (b2MG), was targeted to switch its metabolic pathway from the kidney to the liver. A navigator composed a capturing part and a navigating part was developed as a chimeric protein, and its functions were evaluated. In vitro, immunoprecipitation and competitive inhibition assays showed that the navigator captured b2MG and bound to LDL-receptor, which is highly expressed on hepatocytes, respectively. Additionally, the removal of b2MG from the culture medium of hepatocytes by the navigator was shown in an ELISA. Although the navigator accumulated in the liver when injected intravenously, the body distribution of b2MG in mice unchanged regardless of the introduction of the navigator. In vivo functions of the navigator need to be enhanced.

Report

(3 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Research-status Report
  • Research Products

    (8 results)

All 2016 2015 Other

All Presentation (6 results) (of which Int'l Joint Research: 1 results) Remarks (2 results)

  • [Presentation] 病因物質の代謝経路のスイッチングを行うキメラタンパクナビゲーター分子の開発2016

    • Author(s)
      神戸裕介,山岡哲二
    • Organizer
      日本バイオマテリアル学会シンポジウム2016
    • Place of Presentation
      福岡国際会議場(福岡県福岡市)
    • Year and Date
      2016-11-21
    • Related Report
      2016 Annual Research Report
  • [Presentation] 血中病因物質を捕捉し,異所代謝経路へ誘導するキメラタンパクナビゲーターの開発2016

    • Author(s)
      神戸裕介,山岡哲二
    • Organizer
      第65回高分子学会年次大会
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2016-05-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] Development of chimeric navigator to capture and remove beta2-microglobulin in the blood2016

    • Author(s)
      Kambe Y,Yamaoka T
    • Organizer
      10th World Biomaterials Congress
    • Place of Presentation
      Montreal Convention Center(Montreal,Canada)
    • Year and Date
      2016-05-17
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 血中β2ミクログロブリンの捕捉・除去を行う遺伝子組換えナビゲーター薬剤の開発2016

    • Author(s)
      神戸裕介,山岡哲二
    • Organizer
      第15回日本再生医療学会総会
    • Place of Presentation
      大阪国際会議場(大阪府大阪市)
    • Year and Date
      2016-03-17
    • Related Report
      2015 Research-status Report
  • [Presentation] 血中病因物質の捕捉及び異所代謝経路への誘導を目指したキメラタンパクナビゲーターの開発2015

    • Author(s)
      神戸裕介,山岡哲二
    • Organizer
      第44回医用高分子シンポジウム
    • Place of Presentation
      産業技術総合研究所臨海副都心センター(東京都江東区)
    • Year and Date
      2015-07-27
    • Related Report
      2015 Research-status Report
  • [Presentation] Development of chimeric navigator to capture and remove an etiologic agent in the blood2015

    • Author(s)
      Kambe Y,Yamaoka T
    • Organizer
      第64回高分子学会年次大会
    • Place of Presentation
      札幌コンベンションセンター(北海道札幌市)
    • Year and Date
      2015-05-27
    • Related Report
      2015 Research-status Report
  • [Remarks] 薬物誘導型病因物質除去システム:DNCS

    • URL

      http://www.ncvc.go.jp/res/divisions/biomedical_engineering/13-theme06.html

    • Related Report
      2016 Annual Research Report
  • [Remarks] 薬物誘導型病因物質除去システム:DNCS

    • URL

      http://www.ncvc.go.jp/res/divisions/biomedical_engineering/bme_009.html

    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2018-03-22  

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