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Development of therapeutic systems based on three-dimensional DNA nanostructures

Research Project

Project/Area Number 26293008
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Physical pharmacy
Research InstitutionKyoto University

Principal Investigator

Nishikawa Makiya  京都大学, 薬学研究科(研究院), 准教授 (40273437)

Co-Investigator(Kenkyū-buntansha) 高橋 有己  京都大学, 薬学研究科(研究院), 助教 (00547870)
高倉 喜信  京都大学, 薬学研究科(研究院), 教授 (30171432)
Co-Investigator(Renkei-kenkyūsha) ENDO Masayuki  京都大学, 物質-細胞統合システム拠点, 准教授 (70335389)
WATANABE Hiroshi  京都大学, 化学研究所, 教授 (90167164)
Project Period (FY) 2014-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥17,030,000 (Direct Cost: ¥13,100,000、Indirect Cost: ¥3,930,000)
Fiscal Year 2016: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Keywords核酸 / DNA / DDS / ハイドロゲル / 抗原
Outline of Final Research Achievements

To develop therapeutic systems based on three-dimensional DNA nanostructures, we newly designed several types of basic DNA units. The comparison of their properties revealed that tetrapod-like structured DNA was the DNA nanostructure with the highest formation efficiency and uptake by immune cells. Then, a self-assembling gelling system was developed to obtain DNA hydrogel. Rheological analysis revealed that this hydrogel is injectable because of its quick gel-sol transition, and is regelated after injection. We also found that the antitumor effects of antigen-loaded DNA hydrogel can be greatly improved by the use of cationized antigen, which was more slowly released from the hydrogel than unmodified antigen.

Report

(4 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (37 results)

All 2017 2016 2015 2014

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Acknowledgement Compliant: 9 results,  Open Access: 4 results) Presentation (28 results) (of which Int'l Joint Research: 3 results,  Invited: 7 results)

  • [Journal Article] In vitro and in vivo stimulation of Toll-like receptor 9 by CpG oligodeoxynucleotides incorporated into polypod-like DNA nanostructures2017

    • Author(s)
      Takahashi Y, Maezawa T, Araie Y, Takahashi Y, Takakura Y, Nishikawa M
    • Journal Title

      Journal of Pharmaceutical Sciences

      Volume: 印刷中 Issue: 9 Pages: 2457-2462

    • DOI

      10.1016/j.xphs.2017.03.028

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Self-assembling DNA hydrogel-based delivery of immunoinhibitory nucleic acids to immune cells.2016

    • Author(s)
      Nishida Y, Ohtsuki S, Araie Y, Umeki Y, Endo M, Emura T, Hidaka K, Sugiyama H, Takahashi Y, Takakura Y, Nishikawa M.
    • Journal Title

      Nanomedicine: Nanotechnology, Biology and Medicine

      Volume: 12 Issue: 1 Pages: 123-130

    • DOI

      10.1016/j.nano.2015.08.004

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Polypod-shaped DNAs: small angle x-ray scattering and immunostimulatory activity.2016

    • Author(s)
      Sanada Y, Shiomi T, Okobira T, Tan M, Nishikawa M, Akiba I, Takakura Y, Sakurai K.
    • Journal Title

      Langmuir

      Volume: 印刷中 Issue: 15 Pages: 3760-3765

    • DOI

      10.1021/acs.langmuir.6b00398

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Self-assembling DNA dendrimer for effective delivery of immunostimulatory CpG DNA to immune cells2015

    • Author(s)
      Kohta Mohri, Eri Kusuki, Shozo Ohtsuki, Natsuki Takahashi, Masayuki Endo, Kumi Hidaka, Hiroshi Sugiyama, Yuki Takahashi, Yoshinobu Takakura, Makiya Nishikawa.
    • Journal Title

      Biomacromolecules

      Volume: 16 Issue: 4 Pages: 1095-1101

    • DOI

      10.1021/bm501731f

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Induction of Potent Antitumor Immunity by Sustained Release of Cationic Antigen from a DNA-Based Hydrogel with Adjuvant Activity2015

    • Author(s)
      Yuka Umeki, Kohta Mohri, Yohji Kawasaki, Hiroshi Watanabe, Rei Takahashi, Yuki Takahashi, Yoshinobu Takakura, Makiya Nishikawa
    • Journal Title

      Advanced Functional Materials

      Volume: 25 Issue: 36 Pages: 5758-5767

    • DOI

      10.1002/adfm.201502139

    • NAID

      120005678189

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Optimal Arrangement of Four Short DNA Strands for Delivery of Immunostimulatory Nucleic Acids to Immune Cells2015

    • Author(s)
      Shozo Ohtsuki, Noriyuki Matsuzaki, Kohta Mohri, Masayuki Endo, Tomoko Emura, Kumi Hidaka, Hiroshi Sugiyama, Yuki Takahashi, Kenichi Ishiyama, Norimitsu Kadowaki, Yoshinobu Takakura, Makiya Nishikawa.
    • Journal Title

      Nucleic Acid Therapeutics

      Volume: 25 Issue: 5 Pages: 245-253

    • DOI

      10.1089/nat.2014.0524

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Efficient amplification of self-gelling polypod-like structured DNA by rolling circle amplification and enzymatic digestion2015

    • Author(s)
      T. Yata, Y. Takahashi, K. Hidaka, H. Sugiyama, M. Endo, Y. Takakura, M. Nishikawa
    • Journal Title

      Scientific Reports

      Volume: 5 Issue: 1 Pages: 14979-14979

    • DOI

      10.1038/srep14979

    • NAID

      120005689202

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Atomic force microscopy analysis of orientation and bending of oligodeoxynucleotides in polypod-like structured DNA.2015

    • Author(s)
      Shiomi T, Tan M, Takahashi N, Endo M, Emura T, Hidaka K, Sugiyama H, Takahashi Y, Takakura Y, Nishikawa M.
    • Journal Title

      Nano Research

      Volume: 8 Issue: 12 Pages: 3764-3771

    • DOI

      10.1007/s12274-015-0875-y

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Ishii-Mizuno Y, Umeki Y, Takahashi Y, Kato Y, Takabayashi T, Fujieda S, Takakura Y, Nishikawa M. Nasal delivery of Japanese cedar pollen Cryj1 by using self-gelling immunostimulatory DNA for effective induction of immune responses in mice2015

    • Author(s)
      Ishii-Mizuno Y, Umeki Y, Takahashi Y, Kato Y, Takabayashi T, Fujieda S, Takakura Y, Nishikawa M
    • Journal Title

      Journal of Controlled Release

      Volume: 200 Pages: 52-59

    • DOI

      10.1016/j.jconrel.2014.12.040

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] 抗原内包免疫刺激性DNAハイドロゲルへの免疫細胞の組み込みによる抗腫瘍免疫の増強2017

    • Author(s)
      梅木佑夏、高橋有己、高倉喜信、西川元也
    • Organizer
      日本薬学会第137年会
    • Place of Presentation
      仙台
    • Year and Date
      2017-03-25
    • Related Report
      2016 Annual Research Report
  • [Presentation] ナノ構造化核酸を基盤とする核酸医薬のデリバリー戦略2016

    • Author(s)
      西川元也、高倉喜信
    • Organizer
      日本核酸医薬学会第2年会
    • Place of Presentation
      東京
    • Year and Date
      2016-11-15
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] ヒトMSR-1導入HEK-Blue hTLR9細胞を用いた核酸医薬の免疫活性評価2016

    • Author(s)
      大槻昇三、高橋有己、梅村圭祐、井上貴雄、高倉喜信、西川元也
    • Organizer
      日本核酸医薬学会第2年会
    • Place of Presentation
      東京
    • Year and Date
      2016-11-15
    • Related Report
      2016 Annual Research Report
  • [Presentation] Elucidation of factors determining the cell distribution in artificially fabricated mixed multicellular spheroids for improved insulin secretion2016

    • Author(s)
      Yuya Mizukami, Makiya Nishikawa, Yuki Takahashi, Kazunori Shimizu, Satoshi Konishi, Yoshinobu Takakura
    • Organizer
      Globalization of Pharmaceutics Education Network 2016 (GPEN2016)
    • Place of Presentation
      Lawrence, KS, USA
    • Year and Date
      2016-11-09
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] アジュバント活性を有するDNAハイドロゲルからの抗原徐放化による抗腫瘍免疫の効率的誘導2016

    • Author(s)
      西川元也、高橋有己、高倉喜信
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-06
    • Related Report
      2016 Annual Research Report
  • [Presentation] 核酸医薬の実用化に求められる核酸デリバリーシステムの開発2016

    • Author(s)
      西川元也
    • Organizer
      第32回 日本DDS学会学術集会
    • Place of Presentation
      静岡
    • Year and Date
      2016-06-30
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] Enhanced Activity of Immunosuppressive Oligodeoxynucleotides by Incorporating into Hexapod-like Nanostructured DNA2016

    • Author(s)
      Yuki Araie, Yuki Takahashi, Yoshinobu Takakura, Makiya Nishikawa
    • Organizer
      The 1st Workshop for Japan-Korea Young Scientists on Pharmaceutics
    • Place of Presentation
      京都
    • Year and Date
      2016-06-24
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 免疫刺激性DNAハイドロゲルからのカチオン化抗原の徐放化による抗腫瘍免疫の増強2016

    • Author(s)
      梅木佑夏、高橋有己、高倉喜信、西川元也
    • Organizer
      日本薬剤学会第31年会
    • Place of Presentation
      岐阜
    • Year and Date
      2016-05-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] 光熱免疫療法のための複合材料型DNAハイドロゲルの開発2016

    • Author(s)
      譚萌萌、矢田智也、村上達也、中辻博貴、高橋有己、高倉喜信、西川元也
    • Organizer
      日本薬剤学会第31年会
    • Place of Presentation
      岐阜
    • Year and Date
      2016-05-19
    • Related Report
      2016 Annual Research Report
  • [Presentation] 三次元構造化DNAの免疫細胞および非免疫細胞との相互作用解析2016

    • Author(s)
      大槻昇三,高橋有己,井上貴雄,高倉喜信,西川元也
    • Organizer
      日本薬学会第136年会
    • Place of Presentation
      パシフィコ横浜(神奈川・横浜)
    • Year and Date
      2016-03-26
    • Related Report
      2015 Annual Research Report
  • [Presentation] Polypod-like structured DNA for delivery of bioactive compounds.2016

    • Author(s)
      Makiya Nishikawa
    • Organizer
      University Bordeaux-Kyoto University Mini-Symposium on Biomolecular Science
    • Place of Presentation
      京都大学iCeMS(京都・京都)
    • Year and Date
      2016-01-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] ナノ構造化核酸を基盤とする薬物・核酸デリバリーシステムの開発2016

    • Author(s)
      西川元也
    • Organizer
      第16回遺伝子・デリバリー研究会シンポジウム
    • Place of Presentation
      川崎
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] DNAを基盤とするドラッグデリバリーシステムの開発2016

    • Author(s)
      西川元也
    • Organizer
      第3回 関西バイオ創薬研究会
    • Place of Presentation
      大阪
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 原子間力顕微鏡観察によるpolypodna中のDNA配向性の解明2015

    • Author(s)
      譚 萌萌、塩見朋紀、高橋夏樹、遠藤政幸、江村智子、日高久美、杉山 弘、高橋有己、高倉喜信、西川元也
    • Organizer
      日本核酸医薬学会第1回年会
    • Place of Presentation
      京都テルサ(京都・京都)
    • Year and Date
      2015-11-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] DNAハイドロゲルを利用したCpG DNAの経膣投与による膣粘膜免疫の持続的活性化.2015

    • Author(s)
      野村大貴、高橋有己、高倉喜信、西川元也
    • Organizer
      日本核酸医薬学会第1回年会
    • Place of Presentation
      京都テルサ(京都・京都)
    • Year and Date
      2015-11-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] ナノ構造体化を利用した免疫刺激性DNAによるヒト細胞からのサイトカイン産生の増強2015

    • Author(s)
      大槻昇三、高橋有己、井上貴雄、高倉喜信、西川元也
    • Organizer
      日本核酸医薬学会第1回年会
    • Place of Presentation
      京都テルサ(京都・京都)
    • Year and Date
      2015-11-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] 生体内安定性の向上を目的としたGカルテット構造を組み込んだDNAハイドロゲルの開発と機能評価2015

    • Author(s)
      梅木佑夏、高橋有己、高倉喜信、西川元也
    • Organizer
      日本核酸医薬学会第1回年会
    • Place of Presentation
      京都テルサ(京都・京都)
    • Year and Date
      2015-11-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] RCA法および酵素消化の組み合わせによる自己ゲル化多足型DNA構造体の効率的増幅2015

    • Author(s)
      矢田智也、高橋有己、譚 萌萌、日高久美、遠藤政幸、杉山 弘、高倉喜信、西川元也
    • Organizer
      日本核酸医薬学会第1回年会
    • Place of Presentation
      京都テルサ(京都・京都)
    • Year and Date
      2015-11-30
    • Related Report
      2015 Annual Research Report
  • [Presentation] 免疫細胞への選択的デリバリーを目的としたナノ構造化DNAの開発2015

    • Author(s)
      大槻昇三、西川元也、Tatu Lajunen、毛利浩太、井上貴雄、高橋有己、高倉喜信
    • Organizer
      第31回日本DDS学会学術集会
    • Place of Presentation
      京王プラザホテル(東京)
    • Year and Date
      2015-07-02
    • Related Report
      2015 Annual Research Report
  • [Presentation] 核酸医薬の開発:現状と将来展望2015

    • Author(s)
      西川元也、井上貴雄
    • Organizer
      日本薬剤学会第30年会
    • Place of Presentation
      長崎ブリックホール(長崎・長崎)
    • Year and Date
      2015-05-21
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] 免疫刺激性DNAで構成したDNAハイドロゲルからの抗原徐放化による抗腫瘍免疫誘導の増強.2015

    • Author(s)
      梅木佑夏、西川元也、毛利浩太、高橋有己、高倉喜信
    • Organizer
      遺伝子・デリバリー研究会第15回シンポジウム
    • Place of Presentation
      京都薬科大学(京都・京都)
    • Year and Date
      2015-05-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] DNAハイドロゲルを用いたCryj1の経鼻デリバリーによるスギ花粉症に対する免疫療法の開発2015

    • Author(s)
      水野友美子、梅木佑夏、高橋有己、高倉喜信、西川元也
    • Organizer
      日本薬学会第135年会
    • Place of Presentation
      神戸
    • Year and Date
      2015-03-25 – 2015-03-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] Self-gelatinizable nucleic acid-based sustained delivery of immuno-stimulatory DNA and antigen for induction of antitumor immunity in mice2015

    • Author(s)
      Umeki Y, Nishikawa M
    • Organizer
      第5回発がんスパイラル国際シンポジウム
    • Place of Presentation
      神戸
    • Year and Date
      2015-02-26 – 2015-02-27
    • Related Report
      2014 Annual Research Report
  • [Presentation] 多足型DNAのpod数依存的な溶液内立体構造と細胞取り込みとの相関解析2014

    • Author(s)
      塩見朋紀、西川元也、毛利浩太、真田雄介、櫻井和朗、高橋有己、高倉喜信
    • Organizer
      アンチセンス・遺伝子・デリバリー シンポジウム2014
    • Place of Presentation
      東京
    • Year and Date
      2014-09-08 – 2014-09-09
    • Related Report
      2014 Annual Research Report
  • [Presentation] Optimization of DNA nanostructure for delivery of nucleic acid drugs to immune cells2014

    • Author(s)
      Ohtsuki S, Nishikawa M, Matsuzaki N, Mohri K, Endo M, Hidaka K, Sugiyama H, Takahashi Y, Takakura Y
    • Organizer
      GPEN 2014
    • Place of Presentation
      Helsinki, Finland
    • Year and Date
      2014-08-27 – 2014-08-30
    • Related Report
      2014 Annual Research Report
  • [Presentation] DNAナノテクノロジーを基盤とする核酸医薬のデリバリー2014

    • Author(s)
      西川元也、高倉喜信
    • Organizer
      第30回日本DDS学会学術集会
    • Place of Presentation
      東京
    • Year and Date
      2014-07-30 – 2014-07-31
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] 小角X線散乱による構造解析に基づく多足型DNAの構造活性相関の解明2014

    • Author(s)
      塩見朋紀、西川元也、高橋夏樹、真田雄介、櫻井和朗、高橋有己、高倉喜信
    • Organizer
      日本薬剤学会第29年会
    • Place of Presentation
      大宮
    • Year and Date
      2014-05-20 – 2014-05-22
    • Related Report
      2014 Annual Research Report
  • [Presentation] 免疫刺激性DNAの免疫細胞へのデリバリーのためのDNAナノ構造体の設計2014

    • Author(s)
      大槻昇三、西川元也、毛利浩太、松崎憲幸、遠藤政幸、日高久美、杉山 弘、高橋有己、高倉喜信
    • Organizer
      日本薬剤学会第29年会
    • Place of Presentation
      大宮
    • Year and Date
      2014-05-20 – 2014-05-22
    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2018-03-22  

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