Development of functional polymer-siRNA conjugates for siRNA delivery

• Project/Area Number: 22700489
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Biomedical engineering/Biological material science
• Research Institution: The University of Tokyo
• Principal Investigator: MIYATA Kanjiro 東京大学, 大学院・医学系研究科, 助教 (50436523)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2012: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2011: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: siRNA デリバリー / バイオコンジュゲート材料 / siRNA / ドラッグデリバリー / 機能性高分子 / ポリイオンコンプレックス

Research Abstract

In this study, a smart siRNA-polymer conjugate was developed withan endosome-disrupting polymer via an acidic pH-responsive linkage. Ultimately, theconjugate provided siRNA with enhanced blood circulation property, and further achievedefficient gene silencing in cultured cells, probably due to facilitated endosomal escape ofsiRNA.

Research Products

• [Journal Article] Acidic pH-Responsive siRNA Conjugate for Reversible Carrier Stability and Accelerated Endosoraal Escape with Reduced IFNα -Associated Immune Response (2013)
  • Author(s): Hiroyasu Takemoto, Kanjiro Miyata, Shota Hattori, Takehiko Ishii, Toraoya Suma, Satoshi Uchida, Nobuhiro Nishiyama and Kazunori Kataoka
  • Journal Title: Angewandte Chemie International Edition Volume: 52 Issue: 24 Pages: 6218-6221
  • DOI: 10.1002/anie.201300178
  • Peer Reviewed
• [Journal Article] Silica nanogelling of environment-responsive PEGylated polyplexes for enhanced stability and intracellular delivery of siRNA (2013)
  • Author(s): N. Gouda, K. Miyata
  • Journal Title: Biomaterials Volume: 34 Issue: 2 Pages: 562-570
  • DOI: 10.1016/j.biomaterials.2012.09.077
  • Peer Reviewed
• [Journal Article] 微小な化学構造の違いに基づき低毒性/高効率核酸送達を実現する高分子ナノ材料設計 (2013)
  • Author(s): 宮田完二郎
  • Journal Title: バイオマテリアル-生体材料- Volume: 31 Pages: 26-34
• [Journal Article] A phenylboronate-functionalized polyion complex micelle for ATP-triggered release of siRNA (2012)
  • Author(s): M. Naito, K. Miyata
  • Journal Title: Angew. Chem. Int. Ed Volume: 51 Issue: 43 Pages: 10751-10755
  • DOI: 10.1002/anie.201203360
  • Peer Reviewed
• [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] Accelerated Polymer-Polymer Click Conjugation by Freeze-Thaw Treatment (2012)
  • Author(s): Hiroyasu Takeraoto, Kanjiro Miyata, Shota Hattori, Shigehito Osawa, Nobuhiro Nishiyama, Kazunori Kataoka
  • Journal Title: Bioconjugate Chemsitry Volume: 23 Issue: 8 Pages: 1503-1506
  • DOI: 10.1021/bc300182y
  • 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
• [Journal Article] Targeted polymeric micelles for siRNA treatment of experimental cancer by intravenous injection (2012)
  • Author(s): R. J. Christie, Y. Matsumoto, K. Miyata, T. Nomoto, S. Fukushima, K. Osada, J. Halnaut, F. Pittella, H. -J. Kim, N. Nishiyama, K. Kataoka
  • Journal Title: ACS Nano Volume: 6(6) Issue: 6 Pages: 5174-5189
  • DOI: 10.1021/nn300942b
  • Peer Reviewed
• [Journal Article] Enhanced stability and gene silencing ability of siRNA-loaded polyion complexes formulated from polyaspartamide derivatives with a repetitive array of amino groups in the side chain (2012)
  • Author(s): T.Suma, N.Nishiyama, et al
  • Journal Title: Biomaterials Volume: 33 Issue: 9 Pages: 2770-2779
  • DOI: 10.1016/j.biomaterials.2011.12.022
  • Peer Reviewed
• [Journal Article] Rational design of smart supramolecular assemblies for gene delivery : Chemical challenges in the creation of artificial viruses (2012)
  • Author(s): K. Miyata, N. Nishiyama, K. Kataoka
  • Journal Title: Chem. Soc. Rev Volume: 41(7) Issue: 7 Pages: 2562-2574
  • DOI: 10.1039/c1cs15258k
  • Peer Reviewed
• [Journal Article] PEG-detachable cationic polyaspartamide detivatives bearing stearoyl moieties for systemic siRNA delivery toward subcutaneous BxPC3 pancreatic tumor (2011)
  • Author(s): H.-J.Kim, N.Nishiyama, et al
  • Journal Title: J.Drug Target. Volume: 20 Issue: 1 Pages: 33-42
  • DOI: 10.3109/1061186x.2011.632010
  • Peer Reviewed
• [Journal Article] Odd-even effect of repeating aminoethylene units in the side chain of N-substituted polyaspartamides on gene transfection profiles (2011)
  • Author(s): H.Uchida, N.Nishiyama, et al
  • Journal Title: J.Am.Chem.Soc. Volume: 133 Issue: 39 Pages: 15524-15532
  • DOI: 10.1021/ja204466y
  • Peer Reviewed
• [Journal Article] Effect of polymer structure on micelles formed between siRNA and cationic block copolymer Comprising thiols and amidines (2011)
  • Author(s): R. J. Christie, K. Miyata, Y. Matsumoto, T. Nomoto, D. Menasco, T.-C. Lai, M. Pennisi, K. Osada, S. Fukushima, N. Nishiyama, Y. Yamasaki, K. Kataoka
  • Journal Title: Biomacromolecules Volume: 12(9) Issue: 9 Pages: 3174-3185
  • DOI: 10.1021/bm2006714
  • Peer Reviewed
• [Journal Article] Enhanced endosomal escape of siRNA-incorporating hybrid nanoparticles from calcium phosphate and PEG-block charge-conversional polymer for efficient gene knockdown with negligible cytotoxicity (2011)
  • Author(s): F. Pittella, M. Zhang, Y. Lee, H.-J. Kim, T. Tockary, K. Osada, T. Ishii, K. Miyata, N. Nishiyama
  • Journal Title: Biomaterials Volume: 32(11) Issue: 11 Pages: 3106-3114
  • DOI: 10.1016/j.biomaterials.2010.12.057
  • Peer Reviewed
• [Journal Article] Polymeric micelles for nano-scale drugdelivery (2011)
  • Author(s): K. Miyata, R. J. Christie, K. Kataoka
  • Journal Title: React. Funct. Polym Volume: 71 Issue: 3 Pages: 227-234
  • DOI: 10.1016/j.reactfunctpolym.2010.10.009
• [Journal Article] siRNA-grafted polymer for polyion complex(PIC)-based siRNA delivery : Enhancement of PIC stability and gene silencing efficiency (2010)
  • Author(s): H. Takemoto, A. Ishii, K. Miyata, M. Nakanishi, M. Oba, T. Ishii, Y. Yamasaki, N. Nishiyama, K. Kataoka
  • Journal Title: Biomaterials Volume: 31(31) Issue: 31 Pages: 8097-8105
  • DOI: 10.1016/j.biomaterials.2010.07.015
  • Peer Reviewed
• [Journal Article] Introduction of stearoyl moieties into a biocompatible cationic polyaspartamide derivative, PAsp(DET), with endosomal escaping function for enhanced siRNA-mediated gene knockdown (2010)
  • Author(s): H.-J. Kim, A. Ishii, K. Miyata, Y. Lee, S. Wu, M. Oba, N. Nishiyama, K. Kataoka
  • Journal Title: J. Control. Release Volume: 145(2) Issue: 2 Pages: 141-148
  • DOI: 10.1016/j.jconrel.2010.03.019
  • Peer Reviewed
• [Presentation] siRNA-conjugated charge-conversional polymer as a smart material for siRNA delivery (2013)
  • Author(s): H. Takemoto, K. Miyata
  • Organizer: 16th International Symposium on Recent Advances in Drug Delivery Systems
  • Place of Presentation: シェラトンソルトレイクシティ(ユタ, 米国)
• [Presentation] siRNA-conjugated charge-conversional polymer as a smart material for siRNA delivery (2013)
  • Author(s): Hiroyasu Takemoto, Kanjiro Miyata, et al
  • Organizer: 16th International Symposium on Recent Advances in Drug Delivery Systems
  • Place of Presentation: シェラトンソルトレイクシティ、ユタ州、アメリカ合衆国
• [Presentation] 微小な化学構造の違いに基づいて低毒性/高効率核酸送達を実現する高分子ナノ材料設計 (2012)
  • Author(s): 宮田完二郎
  • Organizer: 2012年度日本バイオマテリアル学会
  • Place of Presentation: 仙台国際センター(宮城県)
  • Year and Date: 2012-11-26
• [Presentation] Fine-tuning of polycationic nanomaterials for enhanced nucleic acid delivery (2012)
  • Author(s): K. Miyata
  • Organizer: 6th Annual Symposium on Nanobiotechnology Kyoto Cell-Material Integration
  • Place of Presentation: 京都大学芝蘭会館(京都府)
  • Year and Date: 2012-11-07
• [Presentation] Design of functional polymeric nanomaterials for nucleic acid delivery (2012)
  • Author(s): K. Miyata
  • Organizer: Oligonucleotide Delivery
  • Place of Presentation: ヘルンシュタイン城(ヘルンシュタイン, オーストリア)
  • Year and Date: 2012-10-09
• [Presentation] Smart multilayered polymer/silica assemblies for enhanced siRNA delivery (2012)
  • Author(s): K. Miyata
  • Organizer: IUMRS-ICEM2012
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2012-09-26
• [Presentation] Self-assembled nanostructures of block copolymers as smart vehicles for gene and siRNA delivery (2012)
  • Author(s): K. Miyata
  • Organizer: ISACS9
  • Place of Presentation: アモイ大学(アモイ、中国)
  • Year and Date: 2012-09-03
• [Presentation] Smart multilayered polymer/silica assemblies for siRNA delivery (2012)
  • Author(s): K. Miyata
  • Organizer: NanoBio Seattle
  • Place of Presentation: ベルハーバーインターナショナルコンベンションセンター(ワシントン州、米国)
  • Year and Date: 2012-07-24
• [Presentation] 核酸デリバリーを指向したカチオン性ポリアミノ酸構造の精密設計 (2012)
  • Author(s): 宮田完二郎
  • Organizer: 第28回日本DDS学会学術集会
  • Place of Presentation: 札幌コンベンションセンター(北海道)
  • Year and Date: 2012-07-04
• [Presentation] siRNAデリバリー用カチオン性ポリアミノ酸設計 (2012)
  • Author(s): 宮田完二郎
  • Organizer: 第61回高分子年次大会
  • Place of Presentation: パシィコ横浜(神奈川県)
  • Year and Date: 2012-05-29
• [Presentation] Development of cationic poly(amino acid)s for preparation of polyion complexes with nucleic acids for efficient gene and siRNA delivery (2012)
  • Author(s): K. Miyata
  • Organizer: ACS Spring 2012 National Meeting & Exposition
  • Place of Presentation: サンディエゴコンベンションセンター(カリフォルニア州、米国)
  • Year and Date: 2012-03-25
• [Presentation] siRNA-grafted Polymer for Efficient siRNA Delivery System (2012)
  • Author(s): H.Takemoto, K.Miyata, et al
  • Organizer: 243rd American Chemical Society National Meeting & Exposition
  • Place of Presentation: Manchester Grand Hyatt(米国カリフォルニア州)
  • Year and Date: 2012-03-25
• [Presentation] Enhanced siRNA-polymer click conjugation after gradual freeze-thawing (2012)
  • Author(s): H. Takemoto, K. Miyata
  • Organizer: The 9th SPSJ International Polymer Conference (IPC2012)
  • Place of Presentation: 神戸国際会議場(兵庫県)
• [Presentation] Enhanced siRNA-polymer click conjugation after gradual freeze-thawing (2012)
  • Author(s): Hiroyasu Takemoto, Kanjiro Miyata, et al
  • Organizer: The 9th SPSJ International Polymer Conference (IPC2012)
  • Place of Presentation: 神戸国際会議場、兵庫県、日本
• [Presentation] 微小な化学構造の違いに基づいて低毒性/高効率核酸送達を実現する高分子ナノ材料設計 (2012)
  • Author(s): 宮田完二郎
  • Organizer: 日本バイオマテリアル学会大会シンポジウム2012
  • Place of Presentation: 仙台国際会議場、宮城県、日本
  • Invited
• [Presentation] Fine-tuning of polycationic nanomaterials for enhanced nucleic acid delivery (2012)
  • Author(s): Kanjiro Miyata, et al
  • Organizer: 6th Annual Symposium on Nanobiotechnology Kyoto Cell-Material Integration 2012
  • Place of Presentation: 京都大学芝蘭会館、京都府、日本
  • Invited
• [Presentation] Design of functional polymeric nanomaterials for nucleic acid delivery (2012)
  • Author(s): Kanjiro Miyata, et al
  • Organizer: Oligonucleotide Delivery: Biology, Engineering and Development
  • Place of Presentation: ヘルンシュタイン城、オーストリア
  • Invited
• [Presentation] 安全かつ高効率な核酸デリバリーに向けたカチオン性ポリアミノ酸設計 (2011)
  • Author(s): 宮田完二郎
  • Organizer: 第21回日本MRS学術シンポジウム
  • Place of Presentation: 横浜情報文化センター(神奈川県)
  • Year and Date: 2011-12-20
• [Presentation] Design of polymeric nanocarrier for siRNA delivery (2011)
  • Author(s): K. Miyata
  • Organizer: France-Japan Workshop-The Nanotech Revolution from Science to Society: A Time for Passion and A Time for Reason
  • Place of Presentation: ENS Cachan(パリ、仏国)
  • Year and Date: 2011-12-15
• [Presentation] Design of Polymeric Nanocarrier for siRNA Delivery (2011)
  • Author(s): K.Miyata, et al
  • Organizer: France-Japan Workshop -The Nanotech Revolution from Science to Society-
  • Place of Presentation: ENS Cahan(仏国パリ)
  • Year and Date: 2011-12-13
• [Presentation] ポリイオンコンプレックス型核酸デリバリーシステム構築に向けたカチオン性ポリアミノ酸構造の検討 (2011)
  • Author(s): 宮田完二郎
  • Organizer: 第60回高分子討論会
  • Place of Presentation: 岡山大学津島キャンパス(岡山県)
  • Year and Date: 2011-09-28
• [Presentation] siRNAグラフト共重合体を基盤とするPIC型スマートキャリアの構築 (2011)
  • Author(s): 武元宏泰、宮田完二郎, 他
  • Organizer: 第60回高分子討論会
  • Place of Presentation: 岡山大学津島キャンパス(岡山県)
  • Year and Date: 2011-09-28
• [Presentation] Efficient siRNA Delivery Using siRNA-grafted Polymer-based Polyion Complexes (2011)
  • Author(s): H.Takemoto, K.Miyata, et al
  • Organizer: 38th Annual Meeting & Exposition of the Controlled Release Society
  • Place of Presentation: Gaylord National Hotel (米国メリーランド州)
  • Year and Date: 2011-08-01
• [Presentation] シリカ被覆型核酸デリバリーキャリアの開発 (2011)
  • Author(s): 宮田完二郎
  • Organizer: 第27回日本DDS学会学術集会
  • Place of Presentation: 東大本郷キャンパス(東京都)
  • Year and Date: 2011-06-10
• [Presentation] siRNA-grafted polymer for polyion complex(PIC)-based siRNA delivery (2011)
  • Author(s): H.Takemoto, K.Miyata, et al
  • Organizer: ICBS2011
  • Place of Presentation: つくば国際会議場(茨城県つくば市)
• [Presentation] 有機無機ハイブリッド型核酸デリバリーキャリアの開発 (2010)
  • Author(s): 宮田完二郎
  • Organizer: 第19回ポリマー材料フォーラム
  • Place of Presentation: 名古屋国際会議場(愛知県)
  • Year and Date: 2010-12-03
• [Presentation] siRNA・ポリアスパラギン酸グラフト共重合体を基盤とするPIC型siRNAデリバリー (2010)
  • Author(s): 武元宏泰、宮田完二郎, 他
  • Organizer: 第59回高分子討論会
  • Place of Presentation: 北海道大学高等教育機能開発総合センター(北海道札幌市)
  • Year and Date: 2010-09-17
• [Presentation] Development of advanced polymer-based nanodevices for siRNA delivery (2010)
  • Author(s): K.Miyata, et al
  • Organizer: 240th ACS National Meeting
  • Place of Presentation: ボストンコンベンションセンター(米国マサチューセッツ州)
  • Year and Date: 2010-08-24
• [Presentation] 高分子を基盤とする遺伝子キャリアのシリカコーティングとその機能評価 (2010)
  • Author(s): 宮田完二郎
  • Organizer: 第26回日本DDS学会学術集会
  • Place of Presentation: 大阪国際交流センター(大阪府)
  • Year and Date: 2010-06-17
• [Presentation] 低毒性かつ高効率な遺伝子導入を可能とする高分子キャリアシステムの設計. (2010)
  • Author(s): 宮田完二郎
  • Organizer: 第59回高分子年次大会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2010-05-27
• [Book] ここまで広がるドラッグ徐放技術の最前線-古くて新しいドラッグデリバリーシステム(DDS)- (2013)
  • Author(s): 武元宏泰、宮田完二郎
  • Total Pages: 376
  • Publisher: メディカルドゥ
• [Remarks]
  • URL: http://www.bmw.t.u-tokyo.ac.jp/
• [Remarks]
  • URL: http://www.cdbim.m.u-tokyo.ac.jp/research/04.php
• [Remarks] 東京大学 片岡研究室ホームページ
  • URL: http://www.bmw.t.u-tokyo.ac.jp/
• [Remarks] 東京大学 大学院医学系研究科 疾患生命工学センター 臨床医工学部門ホームページ
  • URL: http://www.cdbim.m.u-tokyo.ac.jp/research/04.php
• [Remarks]
  • URL: http://first-pg.jp/images/stories/30/09/NewsLetterVol2_j.pdf
• [Remarks] 所属研究室のURL
  • URL: http://www.bmw.t.u-tokyo.ac.jp/
• [Patent(Industrial Property Rights)] アニオン性ポリマー,ニオン性ポリマーを用いたポリイオンコンプレックスおよび三元系ポリマー複合体,ならびに薬学組成物 (2010)
  • Inventor(s): 片岡一則,井篤史,武元宏泰,中西政崇,西山伸宏,田完二郎
  • Industrial Property Rights Holder: 東京大学
  • Filing Date: 2010-07-23