mRNA-based introduction of anti-apoptotic factors using nanomicelle for therapeutic application

• Project/Area Number: 25882011
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Biomedical engineering/Biomaterial science and engineering
• Research Institution: The University of Tokyo
• Principal Investigator: UCHIDA Satoshi 東京大学, 医学(系)研究科(研究院), 助教 (20710726)
• Project Period (FY): 2013-08-30 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: mRNA導入 / 高分子ナノミセル / 遺伝子治療 / 抗アポトーシス因子 / 劇症肝炎 / ハイドロダイナミクス法 / 非ウイルス性キャリア / mRNAデリバリー / アポトーシス関連疾患

Outline of Final Research Achievements

Excessive cell death is associated with various intractable diseases such as fulminant hepatitis, stroke, and myocardial infarction. Gene therapy is a promising approach to these diseases, because it can sustainably provide factors that prevent the cell death, in the body. Although DNA delivery is widely used in a field of gene therapy, we performed messenger RNA (mRNA) delivery to prevent cell death in a disease, in this study, because mRNA delivery can avoid some safety concerns that are associated with DNA delivery. In the treatment of mouse model of fulminant hepatitis, mRNA delivery showed enhanced effect compared to DNA delivery. This result demonstrated the feasibility of the mRNA-based strategy for preventing cell death in diseases.

Research Products

• [Journal Article] A tadpole-shaped gene carrier with distinct phase segregation in a ternary polymeric micelle (2015)
  • Author(s): Chen Q, Osada K, Pennisi M, Uchida S, Tockary TA, Dirisala A, Li Y, Takeda KM, Oniyanagi S, Itaka K, Kataoka K
  • Journal Title: Soft Matter Volume: 11 Issue: 14 Pages: 2718-2722
  • DOI: 10.1039/c4sm02850c
  • Peer Reviewed / Open Access
• [Journal Article] Intrathecal injection of a therapeutic gene-containing polyplex to treat spinal cord injury. (2015)
  • Author(s): Hayakawa K, Uchida S, Ogata T, Tanaka S, Kataoka K, Itaka K.
  • Journal Title: J Control Release Volume: 197 Pages: 1-9
  • DOI: 10.1016/j.jconrel.2014.10.027
  • Peer Reviewed / Acknowledgement Compliant
• [Journal Article] An injectable spheroid system with genetic modification for cell transplantation therapy (2014)
  • Author(s): Uchida S, ltaka K, Nomoto T, Endo T, Matsumoto Y, Ishii T, Kataoka K
  • Journal Title: Biomaterials Volume: 35(8) Issue: 8 Pages: 2499-506
  • DOI: 10.1016/j.biomaterials.2013.12.012
  • Peer Reviewed
• [Journal Article] Optimized rod length of polyplex micelles for maximizing transfection efficiency and their performance in systemic gene therapy against stroma-rich pancreatic tumors (2014)
  • Author(s): Dirisala A, Osada K, Chen Q, Tockary TA, Machitani K, Osawa S, Liu X, Ishii T, Miyata K, Oba M, Uchida S, Itaka K, Kataoka K
  • Journal Title: Biomaterials Volume: 35(20) Issue: 20 Pages: 5359-5368
  • DOI: 10.1016/j.biomaterials.2014.03.037
  • Peer Reviewed / Open Access
• [Journal Article] Muscle-targeted hydrodynamic gene introduction of insulin-like growth factor-1 using polyplex nanomicelle to treat peripheral nerve injury. (2014)
  • Author(s): Nagata K, Itaka K, Baba M, Uchida S, Ishii T, Kataoka K.
  • Journal Title: J Control Release Volume: 183C Pages: 27-34
  • DOI: 10.1016/j.jconrel.2014.03.021
  • Peer Reviewed
• [Journal Article] Targeted gene delivery by polyplex micelles with crowded PEG palisade and cRGD moiety for systemic treatment of pancreatic tumors (2014)
  • Author(s): Z. Ge, Q. Chen, K. Osada, X. Liu, T. A. Tockary, S. Uchida, A. Dirisala, T. Ishii, T. Nomoto, K. Toh, Y. Matsumoto, M. Oba, M. R. Kano, K. Itaka, K. Kataoka
  • Journal Title: Biomaterials Volume: 35 Issue: 10 Pages: 3416-3426
  • DOI: 10.1016/j.biomaterials.2013.12.086
  • Peer Reviewed
• [Journal Article] Tethered PEG Crowdedness Determining Shape and Blood Circulation Profile of Polyplex Micelle Gene Carriers (2013)
  • Author(s): Theofilus A. Tockary, Kensuke Osada, Qixian Chen, Kaori Machitani, Anjaneyulu Dirisala, Satoshi Uchida, Takahiro Nomoto, Kazuko Toh, Yu Matsumoto, Keiji Itaka, Koji Nitta, Kuniaki Nagayama, and Kazunori Kataoka
  • Journal Title: Macromolecules Volume: 46 Issue: 16 Pages: 6585-6592
  • DOI: 10.1021/ma401093z
  • Peer Reviewed
• [Presentation] スフェロイド細胞移植と遺伝子導入の融合システム開発と脊髄損傷治療への応用 (2014)
  • Author(s): 内田 智士, 位髙 啓史, 早川 謙太郎, 緒方 徹, 片岡 一則
  • Organizer: 第36回日本バイオマテリアル学会
  • Place of Presentation: タワーホール船堀, 東京
  • Year and Date: 2014-11-18
• [Presentation] 非ウイルス性遺伝子導入とスフェロイド細胞移植の融合システムを用いた脊髄損傷治療 (2014)
  • Author(s): 内田 智士, 位髙 啓史, 早川 謙太郎, 緒方 徹, 片岡 一則
  • 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: 東京医科歯科大学, 東京
  • Year and Date: 2014-09-09
• [Presentation] mRNA投与による生体内での細胞アポトーシスシグナル制御 (2014)
  • Author(s): 内田 智士, 松井 秋倫, 石井 武彦, 位髙 啓史, 片岡 一則
  • Organizer: 第30回日本DDS学会学術集会
  • Place of Presentation: 慶應義塾大学, 東京
  • Year and Date: 2014-07-30
• [Presentation] Treatment of spinal cord injury by transplantation of BDNF-transfected mesenchymal stem cell spheroids. (2014)
  • Author(s): S. Uchida, K. Itaka, K. Hayakawa, T. Ogata, K. Kataoka
  • Organizer: 17th Annual Meeting of American Society of Gene & Cell Therapy (ASGCT)
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2014-05-22
• [Presentation] BDNF遺伝子導入3次元スフェロイド細胞移植による脊髄損傷治療
  • Author(s): 内田智士、早川謙太郎、緒方徹、片岡一則、位高啓史
  • Organizer: 第13回日本再生医療学会総会
  • Place of Presentation: 国立京都国際会館、京都
• [Presentation] 3次元スフェロイド培養と非ウイルス性遺伝子ベクターを組み合わせた新規細胞移植システムの開発
  • Author(s): 内田智士、位高啓史、遠藤泰輔、柳原歌代子、野本貴大、石井武彦、松本有、片岡一則
  • Organizer: 第35回日本バイオマテリアル学会大会
  • Place of Presentation: タワーホール船堀、東京
• [Presentation] Hydrodynamic delivery of mRNA to mouse liver using polyplex nano micelle.
  • Author(s): S. Uchida, K. Itaka, K. Kataoka
  • Organizer: FIRST合同国際シンポジウム 難治がんを克服する―次世代の診断、治療が描く未来 Overcoming Intractable Cancer- a new path to the future
  • Place of Presentation: 東京大学、東京
• [Book] Nanoparticles in the lung: environmental exposure and drug delivery (Drug and gene delivery in the lungs) (2015)
  • Author(s): S. Uchida, K. Itaka, K. Kataoka
  • Total Pages: 403
  • Publisher: CRC press, Taylor & Francis Group (Florida, USA)
• [Remarks] 東京大学大学院工学系研究科片岡一則研究室ホームページ
  • URL: http://www.bmw.t.u-tokyo.ac.jp/member/suchida.html
• [Patent(Industrial Property Rights)] タンパク質発現を向上させる方法およびタンパク質発現用組成物 (2014)
  • Inventor(s): 位髙啓史, 片岡一則, 池上賢, 内田智士, 他2名
  • Industrial Property Rights Holder: 一般社団法人医療産業イノベーション機構
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2014-090634
  • Filing Date: 2014-04-24
• [Patent(Industrial Property Rights)] ｍＲＮＡ送達用組成物 (2014)
  • Inventor(s): 片岡一則、位高啓史、石井武彦、内田寛邦、内田智士、馬場美雪
  • Industrial Property Rights Holder: 一般社団法人医療産業イノベーション機構
  • Industrial Property Rights Type: 特許
  • Filing Date: 2014-02-12
  • Overseas