siRNA carrier strategy to inhibit to rejection of transplanted kidneys

• Project/Area Number: 24659411
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Kidney internal medicine
• Research Institution: The University of Tokyo
• Principal Investigator: Watanabe Sumiyo 東京大学, 医学(系)研究科(研究院), 研究員 (30422314)
• Co-Investigator(Kenkyū-buntansha): OGASAWARA Toru 東京大学, 医学部附属病院, 講師 (20359623) ; UCHIDA Shunya 帝京大学, 医学部, 教授 (50151882) ; FUKUSHIMA Shigeto 東京大学, 大学院工学系研究科, 研究員 (60625680)
• Project Period (FY): 2012-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000); Fiscal Year 2014: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: 腎移植拒絶反応 / 免疫寛容 / 遺伝子治療 / siRNA / siRNAキャリアー / siRNAキャリア / 核酸治療 / 腎移植拒絶反応抑制 / 癌治療 / 腎不全 / siRNAデリバリー / siRNA治療 / 腎移植

Outline of Final Research Achievements

Japanese economy would collapse in this state by the immeasurable increasing medical costs.Therefore, we aim to reduce the medical costs while providing higher-quality medical care.In the case of kidney dialysis,which takes more than a trillion yen per year and the QOL is low.Meanwhile, kidney transplant requires only one-third of the expense, and the QOL becomes higher.One of the serious problems that transplant is not performed is the low successful rate of engraftment of the transplanted kidneys caused by immunological rejection.On the other hand, suppressing immune system causes many side effects. Therefore, we tried to make recognize transplanted kidneys as "self" to immune system. For the purpose, we designed CD40 and CD40L siRNA and create artificial vector to carry siRNA to the transplanted blood vessels in the transplanted kidneys.

Research Products

• [Journal Article] Influence of RNA strand rigidity on polyion complex formation with block catiomers. (2016)
  • Author(s): K. Hayashi, H. Chaya, S. Fukushima, S. Watanabe, H. Takemoto, K. Osada, N. Nishiyama, K. Miyata, K. Kataoka
  • Journal Title: Macromol. Rapid Commun. Volume: 37 Issue: 6 Pages: 486-493
  • DOI: 10.1002/marc.201500661
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] Multifunctional polyion complex micelle featuring enhanced stability, targetability, and endosome escapability for systemic siRNA delivery to subcutaneous model of lung cancer (2014)
  • Author(s): Hyun Jin Kim, Takehiko Ishii, Meng Zheng, Sumiyo Watanabe, Kazuko Toh, Yu Matsumoto, Nobuhiro Nishiyama, Kanjiro Miyata, Kazunori Kataoka
  • Journal Title: Drug Delivery and Translational Research Volume: 4 Issue: 1 Pages: 50-60
  • DOI: 10.1007/s13346-013-0175-6
  • Peer Reviewed / Open Access
• [Journal Article] Systemic siRNA delivery to a spontaneous pancreatic tumor model in transgenic mice by PEGylated calcium phosphate hybrid micelles (2014)
  • Author(s): F. Pittella, N. Nishiyama, et al.
  • Journal Title: J. Control. Release Volume: 178 Pages: 18-24
  • DOI: 10.1016/j.jconrel.2014.01.008
  • Peer Reviewed / Open Access
• [Journal Article] Functional activities of mutant calcium-sensing receptors determine clinical presentations in patients with autosomal dominant hypocalcemia. (2014)
  • Author(s): Kinoshita Y, Hori M, Taguchi M, Watanabe S, Fukumoto S.
  • Journal Title: J Clin Endocrinol Metab. Volume: 99(2) Pages: 363-368
• [Journal Article] Biomolecular Robotics for Chemomechanically Driven Guest Delivery Fuelled by Intracellular ATP (2013)
  • Author(s): S.Biswas, K.Kinbara, T.Niwa, H.Taguchi, N.Ishii, S.Watanabe, K.Miyata, K.Kataoka and T.Aida
  • Journal Title: Nature Chemistry Volume: 5 Issue: 7 Pages: 613-620
  • DOI: 10.1038/nchem.1681
  • Peer Reviewed
• [Journal Article] ニコランジル 慢性腎不全モデルラットでのポドサイトとマクロファージをターゲットとした新しい治療薬( (2013)
  • Author(s): • 田村 好古(帝京大学 医学部内科学講座), 仲川 孝彦, 浅川 信一郎, 奈倉 倫人, 大野 弘毅, 小菅 正裕, 加藤 秀樹, 野坂 仁也, 渡邉 秀美代, 日野 雅予, 内田 俊也
  • Journal Title: 日本腎臓学会誌 Volume: 55-3 Pages: 346-346
• [Journal Article] 常染色体優性低カルシウム(Ca)血症(ADH)の臨床的重症度と生化学的指標の関係 (2013)
  • Author(s): 木下 祐加, 堀 倫子, 田口 学, 渡邉 秀美代, 福本 誠二
  • Journal Title: 日本内分泌学会雑誌 Volume: 89-1 Pages: 252-252
• [Journal Article] Smart multilayered assembly for biocompatible siRNA delivery featuring dissolvable silica, endosome-disrupting polycation, and detachable PEG (2012)
  • Author(s): T. Suma, K. Miyata
  • Journal Title: ACS Nano Volume: 6 Issue: 8 Pages: 6693-6705
  • DOI: 10.1021/nn301164a
  • Peer Reviewed
• [Journal Article] Pancreatic cancer therapy by systemic administration of VEGF siRNA contained in calcium phosphate/charge-conversional polymer hybrid nanoparticles (2012)
  • Author(s): F. Pittella, K. Miyata
  • Journal Title: J. Control.Release Volume: 161 Issue: 3 Pages: 868-874
  • DOI: 10.1016/j.jconrel.2012.05.005
  • Peer Reviewed
• [Presentation] 1分子siRNA封入ユニットポリイオンコンプレックスの精密構造設計 (2015)
  • Author(s): 宮田完二郎、林光太朗、茶谷洋行、渡邉秀美代、藤加珠子、福島重人、LAN Wanjun、KIM Hyun Jin、武元宏泰、西山伸宏、長田健介、片岡一則
  • Organizer: 第64回高分子討論会
  • Place of Presentation: 宮城県仙台市東北大学
  • Year and Date: 2015-09-17
• [Presentation] Charge number effect of block-ionomers on polygon complex formation with siRNA (2015)
  • Author(s): K. Hayashi, H. Chaya, H. Takemoto, S. Fukushima, S. Watanabe, K. Osada, N. Nishiyama, K. MIyata, K. Kataoka,
  • Organizer: 第64回高分子学会年次大会
  • Place of Presentation: 北海道札幌市札幌イノベーションセンター
  • Year and Date: 2015-05-27
  • Int'l Joint Research
• [Presentation] Enhanced blood circula/on of siRNA complexed with PEG-­‐block-­‐poly(L-­‐lysine) for BxPC3 pancrea/c cancer therapy. (2015)
  • Author(s): Sumiyo Watanabe1, 3, 4, Hiroyuki Chaya1, Takahiro Nomoto5, Shigeto Fukushima2, Kotaro Hayashi2, Kazuko Toh1, Hiroyasu Takemoto2, Xueying Liu1, Yu Matsumoto1, Shunya Uchida3, Masaomi Nangaku4, Kensuke Osada2, Nobuhiro Nishiyama5, Kanjiro Miyata1, Kazunori Kataoka1, 2
  • Organizer: The COINS International Symposium 2015.
  • Place of Presentation: The University of Tokyo, Ito Hall,Tokyo, Japan
  • Year and Date: 2015-02-27
• [Presentation] 1 分子のsiRNA とPEG-カチオン性ポリアミノ酸ブロック共重合体の 複合体形成挙動に対する側鎖構造の影響 (2014)
  • Author(s): 林光太朗・福島重人・石井武彦・長田健介・片岡一則、 東大院医 茶谷洋行・渡邉秀美代・宮田完二郎、西山伸宏
  • Organizer: 高分子学会
  • Place of Presentation: 東北大学
  • Year and Date: 2014-09-15 – 2014-09-17
• [Presentation] ブロック共重合体の精密設計による siRNA ポリイオンコンプレックスの会合状態の制御 (2014)
  • Author(s): 林光太朗・福島重人・石井武彦・長田健介・片岡一則、 東大院医 茶谷洋行・渡邉秀美代・宮田完二郎、 西山伸宏
  • Organizer: 医用高分子研究会
  • Place of Presentation: 産業技術研究所
  • Year and Date: 2014-07-28 – 2014-07-29
• [Presentation] 1 分子のsiRNA からなるポリイオンコンプレックス形成挙動に対する ポリアミノ酸の側鎖アルキル鎖長の効果 (2014)
  • Author(s): 林光太朗・福島重人・石井武彦・長田健介・片岡一則、 東大院医 茶谷洋行・渡邉秀美代・宮田完二郎、 西山伸宏
  • Organizer: 高分子学会年次大会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2014-05-28 – 2014-05-30
• [Presentation] Enhanced Blood Circulation of siRNA complexed with PEG-block-Poly(L-lysine) for BxPC3 pancreatic cancer Treatment. (2014)
  • Author(s): Sumiyo Watanabe, Hiroyuki Chaya, Takahiro Nomoto, Shigeto Fukushima, Kotaro Hayashi, Kazuko Toh, Hiroyasu Takemoto, Xueying Liu, Yu Matsumoto, Shunya Uchida, Masaomi Nangaku, Kensuke Osada, Nobuhiro Nishiyama, Kanjiro Miyata, Kazunori Kataoka
  • Organizer: First international symposium
  • Place of Presentation: The University of Tokyo, Tokyo, Japan
• [Presentation] Enhanced Blood Circulation of siRNA complexed with PEG-block-Poly(L-lysine) for Cancer Treatment. (2013)
  • Author(s): Sumiyo Watanabe, Hiroyuki Chaya, Takahiro Nomoto, Kotaro Hayashi, Shigeto Fukushima, Hiroyasu Takemoto, Kazuko Toh, Xueying Liu, Yu Matsumoto, Shunya Uchida, Masaomi Nangaku, Kensuke Osada, Nobuhiro Nishiyama, Kanjiro Miyata, Kazunori Kataoka
  • Organizer: Controled Release Society
  • Place of Presentation: Conventional center, Honolulu, Hawaii
• [Presentation] Development of single siRNA-loaded polyion complexes with PEG-b-polycations for enhanced systemic delivery of siRNA (2013)
  • Author(s): Kotaro Hayashi, Hiroyuki Chaya, Sumiyo Watanabe, Shigeto Fukushima, Kazuko Toh, Yu Matsumoto, Kensuke Osada, Nobuhiro Nishiyama, Kanjiro Miyata, Kazunori Kataoka
  • Organizer: US-Japan DDS symposium
  • Place of Presentation: Lahaina, Maui, Howaii
• [Presentation] 分子siRNA 封入ポリイオンコンプレックスの構築 ～会合状態に対するPEG-ポリカチオンブロック共重合体の化学構造の効果～ (2013)
  • Author(s): 林光太朗・福島重人・石井武彦・長田健介・片岡一則、 東大院医 茶谷洋行・宮田完二郎・渡邉秀美代・藤加珠子・西山伸宏
  • Organizer: 高分子年次学会
  • Place of Presentation: 京都国際会館
• [Presentation] 分子siRNA 搭載ポリイオンコンプレックス(PICnanocarrier)の構築 (2013)
  • Author(s): 林光太朗・茶谷洋行・渡邉秀美代・宮田完二郎・ 福島重人・長田健介・西山伸宏・片岡一則
  • Organizer: 高分子討論会
  • Place of Presentation: 岡山大学津島キャンパス
• [Presentation] Enhanced longevity of siRNA in bloodstream by fine-tuning of PEG-block-polylysine structures. (2012)
  • Author(s): Sumiyo Watanabe, Hiroyuki Chaya, Kanjiro Miyata, Nobuhiro Nishiyama, Kazunori Kataoka
  • Organizer: Kyoto Cell-Material Integration 2012
  • Place of Presentation: 京都大学
• [Remarks] 東京大学片岡研究室
  • URL: http://www.bmw.t.u-tokyo.ac.jp/index.html
• [Remarks] 片岡研究室
  • URL: http://www.bmw.t.u-tokyo.ac.jp/
• [Remarks] 片岡研究室
  • URL: http://www.bmw.t.u-tokyo.ac.jp/