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Proof-of-concept of nucleic acid medicine for cardiac channelopahy in an animal model

Research Project

Project/Area Number 15K15049
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field General pharmacology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

Furukawa Tetsushi  東京医科歯科大学, 難治疾患研究所, 教授 (80251552)

Research Collaborator IHARA Kensuke  
SASANO Tetsuro  
Project Period (FY) 2015-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywords不整脈 / イオンチャネル / 突然死 / チャネル病 / 核酸医療
Outline of Final Research Achievements

Cardiac channelopathy is a main cause of familiar sudden death; because of lack of efficient therapy, the establishment of novel therapeutic strategy is warrated. I have established an animal model of cardiac channelophy by introducing gain-of-function mutant, with use of which I tried to establish a novel therapeutic strategy of cardiac channelopathy. Originally, I planned to reduce gain-of-function mutant gene using oligonucleic acid. However, oligonucleic acid was mainly introduced into the liver, causing liver toxicity as a side action. Then, I changed our plan to use Crispr/Cas9 genome editing strategy. I was sucdeeded in introducing Crispr/Cas9 vector into cardiomyocytes, genome editing in cardiac myocytes, and modulating cardiac ion channel function.

Report

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

    (42 results)

All 2017 2016 2015

All Journal Article (12 results) (of which Int'l Joint Research: 8 results,  Peer Reviewed: 12 results,  Open Access: 9 results,  Acknowledgement Compliant: 5 results) Presentation (25 results) (of which Int'l Joint Research: 3 results,  Invited: 6 results) Book (5 results)

  • [Journal Article] Intravital imaging of Ca(2+) signals in lymphocytes of Ca(2+) biosensor transgenic mice: indication of autoimmune diseases before the pathological onset.2016

    • Author(s)
      Yoshikawa S, Usami T, Kikuta J, Ishii M, Sasano T, Sugiyama K, Furukawa T, Nakasho E, Takayanagi H, Tedder TF, Karasuyama H, Miyawaki A, Adachi T.
    • Journal Title

      Sci Rep. 2016 Jan 6;6:18738.

      Volume: 6 Issue: 1 Pages: 18738-18738

    • DOI

      10.1038/srep18738

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] High-fat diet increases vulnerability to atrial arrhythmia by conduction disturbance via miR-27b2016

    • Author(s)
      Takahashi K, Sasano T, Sugiyama K, Kurokawa J, Tamura N, Soejima Y, Sawabe M, Isobe M, Furukawa T.
    • Journal Title

      J Mol Cell Cardiol.

      Volume: 90 Pages: 38-46

    • DOI

      10.1016/j.yjmcc.2015.11.034

    • Related Report
      2016 Annual Research Report 2015 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Oxidative Stress Induced Ventricular Arrhythmia and Impairment of Cardiac Function in <i>Nos1ap</i> Deleted Mice2016

    • Author(s)
      Sugiyama K, Sasano T, Kurokawa J, Takahashi K, Okamura T, Kato N, Isobe M and Furukawa T
    • Journal Title

      International Heart Journal

      Volume: 57 Issue: 3 Pages: 341-349

    • DOI

      10.1536/ihj.15-471

    • NAID

      130005153706

    • ISSN
      1349-2365, 1349-3299
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Genetic defects in a His-Purkinje system transcription factor, IRX3, cause lethal cardiac arrhythmias.2016

    • Author(s)
      Koizumi A, Sasano T, Kimura W, Miyamoto Y, Aiba T, Ishikawa T, Nogami A, Fukamizu S, Sakurada H, Takahashi Y, Nakamura H, Ishikura T, Koseki H, Arimura T, Kimura A, Hirao K, Isobe M, Shimizu W, Miura N, Furukawa T.
    • Journal Title

      European Heart Journal.

      Volume: 37 (18) Issue: 18 Pages: 1469-1475

    • DOI

      10.1093/eurheartj/ehv449

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] A distribution analysis of action potential parameters obtained from patch-clamped human stem cell-derived cardiomyocytes.2016

    • Author(s)
      Lopez-Redondo F, Kurokawa J, Nomura F, Kaneko T, Hamada T, Furukawa T, Yasuda K
    • Journal Title

      J Pharmacol Sci

      Volume: 131 Issue: 2 Pages: 141-145

    • DOI

      10.1016/j.jphs.2016.04.015

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Novel dielectric coagulation identifies hypercoagulability in patients with a high CHADS2 score without atrial fibrillation2016

    • Author(s)
      99. Hasegawa Y, Hamada S, Nishimura T, Sasaki T, Ebana Y, Kawabata M, Goya M, Isobe M, Koyama T, Furukawa T, Hirao K, Sasano T
    • Journal Title

      PLoS ONE

      Volume: 11 Issue: 6 Pages: e0156557-e0156557

    • DOI

      10.1371/journal.pone.0156557

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Partial IK1 blockade destabilizes spiral wave rotation center without inducing wave breakup and facilitates termination of reentrant arrhythmias in ventricles2016

    • Author(s)
      Kushiyama Y, Honjo H, Niwa R, Takanari H, Yamazaki M, Takemoto Y, Sakuma I, Kodama I, Kamiya K
    • Journal Title

      American Journal of Physiology Heart and Circulatory Physiology

      Volume: 311 Issue: 1 Pages: 750-758

    • DOI

      10.1038/srep34198

    • NAID

      120005946586

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genetic variants associated with susceptibility to atrial fibrillation in Japanese population2016

    • Author(s)
      Liu L, Ebana Y, Nitta JI, Takahashi Y, Miyazaki S, Tanaka T, Komura M, Isobe M, Furukawa T
    • Journal Title

      Canadean Journal of Cardiology

      Volume: 33 Issue: 4 Pages: 443-449

    • DOI

      10.1016/j.cjca.2016.10.029

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Screening system for drug-induced arrhythmogenic risk combining patch clamp and a heart simulator.2015

    • Author(s)
      Okada J, Yoshinaga T, Kurokawa J, Washio T, Furukawa T, Sawada K, Sugiura S, Hisada T.
    • Journal Title

      Sience Advances

      Volume: 1 Issue: 4

    • DOI

      10.1126/sciadv.1400142

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Aromatase knockout mice reveal an impact of estrogen on drug-induced alternation of murine electrocardiography parameters2015

    • Author(s)
      Kurokawa, J., Sasano, T., Kodama, M., Li, M., Ebana, Y., Harada, N., Honda, S.-I., Nakaya, H., & Furukawa, T.
    • Journal Title

      J. Toxicol. Sci.

      Volume: 40 Issue: 3 Pages: 339-348

    • DOI

      10.2131/jts.40.339

    • NAID

      130005068413

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Strategies for heart regeneration: approaches ranging from induced pluripotent stem cells to direct cardiac reprogramming.2015

    • Author(s)
      Yamakawa H, Ieda M.
    • Journal Title

      Int Heart J

      Volume: 56 Issue: 6 Pages: 1-5

    • DOI

      10.1016/j.stemcr.2015.10.019

    • Related Report
      2015 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Enhancement of spontaneous activity by HCN4 overexpression in mouse embryonic stem cell-derived cardiomyocytes:A possible biological pacemaker2015

    • Author(s)
      Saito Y, Nakamura K, Yoshida M, Sugiyama H, Ohe T, Kurokawa J, Furukawa T, Takano M, Nagase S, Morita H,. Kusano KF, Ito H.
    • Journal Title

      PLoS ONE

      Volume: 10

    • Related Report
      2015 Research-status Report
    • Peer Reviewed
  • [Presentation] 女性ホルモンが心電図QT間隔に与える影響2016

    • Author(s)
      田村文弥、家田真樹、鈴木岳之、福田恵一、中谷晴昭、原田信広、古川哲史、 黒川洵子
    • Organizer
      日本適応医 学会学術集会
    • Place of Presentation
      東京コンベンションセンター
    • Year and Date
      2016-12-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] ヒト iPS由来心筋細胞の動きベクトル解析による抗がん剤心毒性の評価法2016

    • Author(s)
      黒川洵子、児玉昌美、高橋健太郎、諫田泰成、古川哲史
    • Organizer
      第26回日 本循環薬理学会
    • Place of Presentation
      信州大学
    • Year and Date
      2016-12-02
    • Related Report
      2016 Annual Research Report
  • [Presentation] Individual evaluation of whole blood coagulability and factor Xa activity by novel dielectric blood coagulometry2016

    • Author(s)
      Sasano T, Hamada S, Hasegawa Y, Nishimura T, Yoshitake T, Shiohira S, Sasaki T, Kawabata M, Goya M, Isobe M, Furukawa T, Hirao K
    • Organizer
      第63回日本不整脈心電学会学術大会
    • Place of Presentation
      札幌コンベンションセンター
    • Year and Date
      2016-07-17
    • Related Report
      2016 Annual Research Report
  • [Presentation] Common genetic variants indicate the risk of atrial fibrillation in Japanese population2016

    • Author(s)
      Lian Liu, Yusuke Ebana, Jun-ichi Nitta, Yoshihide Takahashi, Shinsuke Miyazaki, Toshihiro Tanaka, Masatoshi Komura, Mitsuaki Isobe, Tetsushi Furukawa.
    • Organizer
      第63回日本不整脈心電学会学術大会
    • Place of Presentation
      札幌コンベンションセンター
    • Year and Date
      2016-07-16
    • Related Report
      2016 Annual Research Report
  • [Presentation] トランスジェニックマウスを利用した心筋遅延整流性カリ ウムチャネル分子複合体の探索と解析2016

    • Author(s)
      福田俊、児玉昌美、永森收志,五十棲規嘉、藤塚美紀,金井好克,古川哲史, 黒川洵子
    • Organizer
      第134回日本薬理学会関東部会
    • Place of Presentation
      国際医療福祉大学
    • Year and Date
      2016-07-09
    • Related Report
      2016 Annual Research Report
  • [Presentation] Oxidative Stress Induced Ventricular Arrhythmia and Impairment of Cardiac Function in Nos1ap Deleted Mice2016

    • Author(s)
      Sasano T, Sugiyama K, Kurokawa J, Takahashi K, Okamura T, Kato N, Isobe M, Furukawa T
    • Organizer
      The 9th international conference on the biology, chemistry, and therapeutic approach of Nitric Oxide
    • Place of Presentation
      仙台
    • Year and Date
      2016-05-22
    • Related Report
      2016 Annual Research Report
  • [Presentation] Regulation of cardiac L-type Ca2+ channel via a progesterone receptor2016

    • Author(s)
      Kurokawa J, Kodama M, Furukawa T
    • Organizer
      The 9th international conference on the biology, chemistry, and therapeutic approach of Nitric Oxide
    • Place of Presentation
      仙台
    • Year and Date
      2016-05-22
    • Related Report
      2016 Annual Research Report
  • [Presentation] Gene-Guided Therapy in AF2016

    • Author(s)
      Furukawa T, Liu L, Ebana Y, Nitta J, Takahashi Y, Miyazaki M, Isobe M, Tanaka T
    • Organizer
      Heart Rhythm Society's 37th Annual Scientific Sessions
    • Place of Presentation
      サンフランシスコ
    • Year and Date
      2016-05-06
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Contribution of pannexin-1 to cardioprotection and arrhythmogenicity induced by ischemia/reperfusion injury2016

    • Author(s)
      Takahashi K, Sasano T, Sugiyama K, Isobe M, Furukawa T
    • Organizer
      The 80th Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      仙台国際センター(宮城県/仙台市)
    • Year and Date
      2016-03-18
    • Related Report
      2015 Research-status Report
  • [Presentation] The occurrence of ectopy from pulmonary veins in atrial fibrillation in middle-aged women2016

    • Author(s)
      Hayashi Y, Nitta J, Iwasaki T, Lee K, Watanabe K, Hirao T, Kato N, Inamura Y, Suzuki M, Negi K, Satoh A, Yamato T, Matsumurea Y, Asakawa K, Ebana Y, Furukawa T, Gohya M, Hirao K, Isobe M
    • Organizer
      The 80th Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      仙台国際センター(宮城県/仙台市)
    • Year and Date
      2016-03-18
    • Related Report
      2015 Research-status Report
  • [Presentation] Neurl, ubiquitin E3 ligase, contributes to the maintenance of sarcomere structure and the regulation of autophagy2016

    • Author(s)
      Ito S, Ebana Y, Furukawa T
    • Organizer
      The 80th Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      仙台国際センター(宮城県/仙台市)
    • Year and Date
      2016-03-18
    • Related Report
      2015 Research-status Report
  • [Presentation] The genotype of SNPs related whether ectopy is from pulmonary vein or others in atrial fibrillation2016

    • Author(s)
      Hayashi Y, Nitta J, Iwasaki T, Lee K, Watanabe K, Hirao T, Kato N, Inamura Y, Suzuki M, Negi K, Satoh A, Yamato T, Matsumurea Y, Asakawa K, Ebana Y, Furukawa T, Gohya M, Hirao K, Isobe M
    • Organizer
      The 80th Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      仙台国際センター(宮城県/仙台市)
    • Year and Date
      2016-03-18
    • Related Report
      2015 Research-status Report
  • [Presentation] Novel dielectric blood coagulometry can evaluate factor Xa and thrombin activity individually2016

    • Author(s)
      Hamada S, Hasegawa Y, Nishimura T, Furukawa T, Isobe M, Hirao K, Sasano T
    • Organizer
      The 80th Annual Scientific Meeting of the Japanese Circulation Society
    • Place of Presentation
      仙台国際センター(宮城県/仙台市)
    • Year and Date
      2016-03-18
    • Related Report
      2015 Research-status Report
  • [Presentation] トランスジェニックマウスを利用した心筋IKsチャネル分子複合体の網羅的解析2016

    • Author(s)
      福田俊、児玉昌美、永森収志、五十嵐規、藤森美紀、金井好克、古川哲史、黒川洵子
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県/横浜市)
    • Year and Date
      2016-03-09
    • Related Report
      2015 Research-status Report
  • [Presentation] 内向き整流カリウムチャネルを過剰発現させたヒトiPS由来心筋細胞を用いた薬理作用解析2016

    • Author(s)
      林英里奈、木村麗子、李敏、安東朋子、関野祐子、古川哲史、諫田泰成、黒川洵子
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県/横浜市)
    • Year and Date
      2016-03-09
    • Related Report
      2015 Research-status Report
  • [Presentation] 胎生マウスの冠血管形成に見られる性差2016

    • Author(s)
      児玉昌美、古川哲史、黒川洵子
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県/横浜市)
    • Year and Date
      2016-03-09
    • Related Report
      2015 Research-status Report
  • [Presentation] ヒトiPS細胞由来心筋の活動電位形成に関連する遺伝子の定量的発現解析におけるリファレンス遺伝子の選定2016

    • Author(s)
      木村麗子、児玉昌美、古谷和春、諫田泰成、倉智嘉久、関野祐子、古川哲史、黒川洵子
    • Organizer
      第89回日本薬理学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県/横浜市)
    • Year and Date
      2016-03-09
    • Related Report
      2015 Research-status Report
  • [Presentation] Functional evaluation of murine cardiomyocytes using motion imaging technique2016

    • Author(s)
      Kurokawa J, Takahashi K, Furukawa T
    • Organizer
      日本安全性薬理研究会
    • Place of Presentation
      東京大学(東京都/文京区)
    • Year and Date
      2016-02-19
    • Related Report
      2015 Research-status Report
  • [Presentation] マウス冠血管形成における性差の起源の探索2015

    • Author(s)
      児玉昌美、古川哲史、黒川洵子
    • Organizer
      第38回日本分子生物学会・第88回日本成果学会合同大会
    • Place of Presentation
      神戸ポートアイランド(兵庫県/神戸市)
    • Year and Date
      2015-12-02
    • Related Report
      2015 Research-status Report
  • [Presentation] iPS cells and arrhythmia mechanism2015

    • Author(s)
      Tetsushi Furukawa
    • Organizer
      2015 8th APHRS
    • Place of Presentation
      メルボルン国際会議場メルボルン市(オーストラリア)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Oxidative stress induced ventricular arrhythmia and impairment cardiac function in Nos1ap deleted mice2015

    • Author(s)
      Koji Sugiyama, Tetsuo Sasano, Tetsushi Furukawa
    • Organizer
      2015 8th APHRS
    • Place of Presentation
      メルボルン国際会議場メルボルン市(オーストラリア)
    • Year and Date
      2015-11-18
    • Related Report
      2015 Research-status Report
    • Int'l Joint Research
  • [Presentation] Study of long QT syndrome type 3 using human iPS cell-derived cardiomyocytes2015

    • Author(s)
      Tetsushi Furukawa, Shiniachi Okata, Shinsuke Yuasa, 他17名
    • Organizer
      第30回不整脈学会学術集会・第32回日本心電学会学術集会
    • Place of Presentation
      国立京都国際会議場(京都府/京都市)
    • Year and Date
      2015-07-28
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 心房細動はなぜ慢性化するのか:そのメカニズムと対策2015

    • Author(s)
      古川哲史
    • Organizer
      第30回不整脈学会学術集会・第32回日本心電学会学術集会
    • Place of Presentation
      国立京都国際会議場(京都府/京都市)
    • Year and Date
      2015-07-28
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 不整脈医が知っておくべきこと2015

    • Author(s)
      古川哲史
    • Organizer
      第30回不整脈学会学術集会・第32回日本心電学会学術集会
    • Place of Presentation
      国立京都国際会議場(京都府/京都市)
    • Year and Date
      2015-07-28
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 心房細動とアンチエイジング2015

    • Author(s)
      古川哲史
    • Organizer
      第15回日本抗加齢医学会総会
    • Place of Presentation
      福岡国際会議場(福岡県/福岡市)
    • Year and Date
      2015-05-30
    • Related Report
      2015 Research-status Report
    • Invited
  • [Book] 循環器薬の選び方と使い分け2017

    • Author(s)
      古川哲史
    • Total Pages
      147
    • Publisher
      総合医学社
    • Related Report
      2016 Annual Research Report
  • [Book] 循環器治療薬パーフェクトガイド2016

    • Author(s)
      古川哲史
    • Total Pages
      132
    • Publisher
      総合医学社
    • Related Report
      2016 Annual Research Report 2015 Research-status Report
  • [Book] 心臓イオンチャネルA to Z2015

    • Author(s)
      古川哲史
    • Total Pages
      168
    • Publisher
      ライフメディコム
    • Related Report
      2015 Research-status Report
  • [Book] 目からウロコの心電図[改訂版]2015

    • Author(s)
      古川哲史
    • Total Pages
      145
    • Publisher
      ライフメディコム
    • Related Report
      2015 Research-status Report
  • [Book] そうだったのか!臨床に役立つ心臓の発生・再生2015

    • Author(s)
      古川哲史
    • Total Pages
      178
    • Publisher
      メディカル・サイエンス・インターナショナル
    • Related Report
      2015 Research-status Report

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

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