Development of polypodna based dendritic nano-sized DDS

• Project/Area Number: 26860021
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Physical pharmacy
• Research Institution: Setsunan University
• Principal Investigator: Mohri Kohta 摂南大学, 薬学部, 助教 (30723697)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2016: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 核酸 / ナノ粒子 / DDS / CpGモチーフ / DNA assembly / dendritic structure / CpG motif / macrophage / innate immunity

Outline of Final Research Achievements

To increase the therapeutic potency of immunostimulatory CpG DNA, we tried to develop polypod-like structured DNA, or polypodna based dendritic nano-sized DDS. We succeeded in constructing dendritic-like DNA (DL-DNA) by connecting polypodnas through their adhesive terminal ends, but not ligating with enzymatic reaction. Furthermore, we found that DL-DNA was efficiently taken up by immune cells, which dramatically increased the cytokine release by CpG DNA. Thus, we have shown that the DL-DNA developed by this approach, can be an useful nano-sized DDS for increasing the potency of nucleic acid drugs.

Research Products

• [Journal Article] Optimal Arrangement of Four Short DNA Strands for Delivery of Immunostimulatory Nucleic Acids to Immune Cells (2015)
  • 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
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] Self-assembling DNA dendrimer for effective delivery of immunostimulatory CpG DNA to immune cells (2015)
  • 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
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] Kissing-loop相互作用を介して多足型DNA構造体を連結したDNAハイドロゲルの開発 (2017)
  • Author(s): 野々村茉緒，毛利浩太，西川元也，佐久間信至
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-25
• [Presentation] グアニンを豊富に含むオリゴヌクレオチドを付与した多足型DNA構造体のがん細胞指向性の評価 (2017)
  • Author(s): 松下奈央，毛利浩太，林英美，西野真名仁，西川元也，佐久間信至
  • Organizer: 日本薬学会第137年会
  • Place of Presentation: 仙台
  • Year and Date: 2017-03-25
• [Presentation] がん指向性の向上を目的としたguanine-richオリゴヌクレオチドを付与した多足型DNA構造体の開発．第32回日本DDS学会学術集会 (2016)
  • Author(s): 林英美，毛利浩太，西川元也，西野真名仁，谷下宗平，佐久間信至
  • Organizer: 第32回日本DDS学会学術集会
  • Place of Presentation: 静岡
  • Year and Date: 2016-07-01
• [Presentation] Polypodna構造によるCpG DNAの免疫活性増強メカニズムの解明 (2016)
  • Author(s): 永田健吾，毛利浩太，外山詩栞，高橋有己，高倉喜信，西川元也，佐久間信至
  • Organizer: 日本薬剤学会第31年会
  • Place of Presentation: 岐阜
  • Year and Date: 2016-05-21
• [Presentation] 多足型構造体によるCpG DNAの免疫活性増強メカニズムの解析． (2015)
  • Author(s): 外山詩栞，永田健悟，毛利浩太，西川元也，高橋有己，高倉喜信，佐久間信至．
  • Organizer: 第65回日本薬学会近畿支部総会・大会
  • Place of Presentation: 大阪大谷大学（大阪）
  • Year and Date: 2015-10-17
• [Presentation] Elucidation of the Mechanism of Increased Activity of Immunostimulatory DNA by Formation of Polypod-like Structure. (2015)
  • Author(s): Kohta Mohri, Makiya Nishikawa, Shiori Toyama, Kengo Nagata, Yuki Takahashi, Yoshinobu Takakura, Shinji Sakuma.
  • Organizer: The 42nd Annual Meeting & Exposition of the Controlled Release Society,
  • Place of Presentation: Edinburgh International Conference Centre (Edinburgh, Scotland)
  • Year and Date: 2015-07-28
  • Int'l Joint Research
• [Presentation] Elucidation of the Mechanism of Increased Activity of Immunostimulatory DNA by Formation of Polypod-like Structure (2015)
  • Author(s): Kohta Mohri, Makiya Nishikawa, Shiori Toyama, Kengo Nagata, Yuki Takahashi, Yoshinobu Takakura, Shinji Sakuma.
  • Organizer: The 42nd Annual Meeting & Exposition of the Controlled Release Society
  • Place of Presentation: Edinburgh International Conference Centre (Edinburgh, Scotland)
  • Year and Date: 2015-07-26 – 2015-07-29
• [Presentation] がん指向性DNA構造体の開発を目的としたG-rich DNAアプタマーの基礎検討． (2015)
  • Author(s): 谷下宗平，林英美，毛利浩太，西川元也，佐久間信至．
  • 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
• [Presentation] 免疫刺激性CpG DNAデリバリーのための自己組織型DNAデンドリマーの開発 (2015)
  • Author(s): 毛利浩太
  • Organizer: 日本薬剤学会英語セミナー
  • Place of Presentation: 慶応義塾大学薬学部芝共立キャンパス（東京）
  • Year and Date: 2015-03-13
• [Remarks] 摂南大学薬学部 薬物送達学研究室
  • URL: http://www.labonet.info/sakuma/index.html