Kinetic-based analysis for quantized folding of closed-circular DNA

• Project/Area Number: 22750098
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Polymer chemistry
• Research Institution: The University of Tokyo
• Principal Investigator: OSADA Kensuke 東京大学, 大学院・工学系研究科, 准教授 (10396947)
• 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: 生体関連高分子 / DNA 凝縮 / 生体材料 / 高分子構造・物性 / ナノバイオ / 遺伝子

Research Abstract

Mechanistic analysis for structural formation of polyplex micelles as gene delivery system was demonstrated. Main object of this work was placed on understanding principle factors to determine the folding number of plasmid DNA (pDNA) within the polyplex micelles, where pDNA is packaged by highly regulated folding manner, namely quantized folding scheme. The research performed on a basis of kinetic analysis approved that folding process of pDNA is consistently described in the same way as kinetics of polymer crystallization. The deeper understanding on the structure formation of polyplex micelles enables secure molecular design for promoting effective gene delivery carriers.

Research Products

• [Journal Article] Bioactivepolymeric metallosomesself-assembled through blockcopolymer-metal complexation. (2012)
  • Author(s): K. Osada, H. Cabral, Y. Mochida, S. -ELee, K. Nagata, T. Matsuura, M.Yamamoto, Y. Anraku, A. Kishimura, N.Nishiyama, K. Kataoka
  • Journal Title: J. Am.Chem. Soc. Volume: 134(32) Issue: 32 Pages: 13172-13175
  • DOI: 10.1021/ja304615y
  • Peer Reviewed
• [Journal Article] Effective transgene expression without toxicity by intraperitoneal administration of PEG-detachable polyplex micelles in mice with peritoneal dissemination (2012)
  • Author(s): M.Kumagai, N.Nishiyama, et al.
  • Journal Title: J.Control.Release Volume: (in press)(印刷中)(掲載確定) Issue: 3 Pages: 542-551
  • DOI: 10.1016/j.jconrel.2012.03.021
  • 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] PEGylated polyplex with optimized PEG shielding enhances gene introduction in lungs by minimizing inflammatory responses (2012)
  • Author(s): Uchida S
  • Journal Title: Mol Ther Volume: 20(6) Issue: 6 Pages: 1196-1203
  • DOI: 10.1038/mt.2012.20
  • Peer Reviewed
• [Journal Article] Homo-catiomer integration into PEGylated polyplex micelle from block-catiomer for systemic antiangiogenic gene therapy for fibrotic pancreatic tumors (2012)
  • Author(s): Q.Chen, K.Osada, T.Ishii, M.Oba, S.Uchida, T.A.Tockary, T.Endo, Z.Ge, H.Kinoh, M.R.Kano, K.Itaka, K.Kataoka
  • Journal Title: Biomaterials Volume: (in press) Issue: 18 Pages: 4722-4730
  • DOI: 10.1016/j.biomaterials.2012.03.017
  • Peer Reviewed
• [Journal Article] Enhanced gene expression promoted by the quantized folding of pdna within polyplex micelles (2012)
  • Author(s): K. Osada, T. Shiotani, T. A. Tockary, D. Kobayashi, H. Oshima, S. Ikeda, R. J. Christie, K. Itaka, K. Kataoka
  • Journal Title: Biomaterials Volume: 33 Issue: 1 Pages: 325-332
  • DOI: 10.1016/j.biomaterials.2011.09.046
  • Peer Reviewed
• [Journal Article] Ultrasound-Mediated Gene Transfection In vitro: Enhanced Efficiency by Complexation of Plasmid DNA (2012)
  • Author(s): (Y. Zhang), R. Tachibana, A. Okamoto, T. Azuma, A. Sasaki, K. Yoshinaka, K. Osada, K. Kataoka, S. Takagi, Y. Matsumoto
  • Journal Title: Japanese Journal of Applied Physics Volume: 51 Issue: 7S Pages: 07GF29-07GF29
  • DOI: 10.1143/jjap.51.07gf29
  • 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] Combination of Chondroitin Sulfate and Polyplex Micelles from Poly(ethylene glycol)-poly{N'-[N-(2-aminoethyl)-2-aminoethyl]aspartamide} Block Copolymer for Prolonged In Vivo Gene Transfection with Reduced Toxicity (2011)
  • Author(s): Uchida S, Itaka K, Chen Q, Osada K, Miyata K, Ishii T, Harada-Shiba M, Kataoka K
  • Journal Title: J Control Release Volume: 2 Issue: 2 Pages: 296-302
  • DOI: 10.1016/j.jconrel.2011.04.026
  • Peer Reviewed
• [Journal Article] Polylex micelles prepared from ω-cholesteryl PEG-polycation block copolymers for systemic gene delivery (2011)
  • Author(s): M.Oba, K.Miyata, K.Osada, R.J.Christie, M.Sanjoh, W.Li, S.Fukushima, T.Ishii, M.R.Kano, N.Nishiyama, H.Koyama, K.Kataoka
  • Journal Title: Biomaterials Volume: 32(2) Issue: 2 Pages: 652-663
  • DOI: 10.1016/j.biomaterials.2010.09.022
  • 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): Frederico Pittella, Mingzhen Zhang, Yan Lee, Hyun Jin Kim, Theofilus Tockary, Kensuke Osada, Takehiko Ishii, Kanjiro Miyata, Nobuhiro Nishiyama, Kazunori Kataoka
  • Journal Title: Biomaterials Volume: 32 Pages: 3106-3114
  • Peer Reviewed
• [Journal Article] Polyplex micelles prepared from ω-cholesteryl PEG-polycation block copolymers for systemic gene delivery (2011)
  • Author(s): Makoto Oba, Kanjiro Miyata, Kensuke Osada, James R.Christie, Mai Sanjoh, Weidong Li, Shigeto Fukushima, Takehiko Ishii, Mitsunobu R.Kano, Nobuhiro Nishiyama, Hiroyuki Koyama, Kazunori Kataoka
  • Journal Title: Biomaterials Volume: 32 Pages: 652-663
  • Peer Reviewed
• [Journal Article] Quantized folding of plasmid DNA condensed with block catiomer into characteristic rod structures promoting transgene efficacy (2010)
  • Author(s): K. Osada, H. Oshima, D. Kobayashi, M. Doi, M. Enoki, Y. Yamasaki, K. Kataoka
  • Journal Title: J. Am. Chem. Soc. Volume: 132 (35) Issue: 35 Pages: 12343-12348
  • DOI: 10.1021/ja102739b
  • Peer Reviewed
• [Journal Article] Polyplex nanomicelle promotes hydrodynamic gene introduction to skeletal muscle (2010)
  • Author(s): K. Itaka, K. Osada, K. Morii, P. Kim, S. -H. Yun, K. Kataoka
  • Journal Title: J. Control. Release Volume: 143 (1) Issue: 1 Pages: 112-119
  • DOI: 10.1016/j.jconrel.2009.12.014
  • Peer Reviewed
• [Journal Article] Quantized Folding of Plasmid DNA Condensed with Block Catiomer into Characteristic Rod Structures Promoting Transgene Efficacy (2010)
  • Author(s): Kensuke Osada, Hiroki Oshima, Daigo Kobayashi, Motoyoshi Doi, Manabu Enoki, Yuichi Yamasaki, Kazunori Kataoka
  • Journal Title: J.Am.Chem.Soc. Volume: 132 Pages: 12343-12348
  • Peer Reviewed
• [Journal Article] Enhanced in vivo Magnetic Resonance Imaging of Tumors by PEGylated Iron-Oxide-Gold Core-Shell Nanoparticles with Prolonged Blood Circulation Properties (2010)
  • Author(s): Michiaki Kumagai, Tridib Kumar Sarma, Horacio Cabral, Sachiko Kaida, Masaki Sekino, Nicholas Herlambang, Kensuke Osada, Mitsunobu R.Kano, Nobuhiro Nishiyama, Kazunori Kataoka
  • Journal Title: Macromol.Rapid.Commun. Volume: 31 Pages: 1521-1528
  • Peer Reviewed
• [Presentation] 環状DNAの折り畳みと遺伝子治療への応用 (2013)
  • Author(s): (長田健介)、片岡一則
  • Organizer: 第22回インテリジェント材料フォーラムシステムシンポジウム
  • Place of Presentation: 東京女子医科大学 先端生命医科学研究所、東京
• [Presentation] Rod or globute, that is a question (2013)
  • Author(s): (長田健介)、片岡一則
  • Organizer: 高分子基礎研究会 2013
  • Place of Presentation: 国民宿舎 仙酔島
• [Presentation] Control of pDNA packaging for gene delivery (2013)
  • Author(s): (K. Osada), Q. Chen, T. A. Tockary, A. Dirisala, Y. Li, K. Machitani, K. Kataoka
  • Organizer: 2nd International Conference on Biomaterials Science in Tsukuba ICBS2013
  • Place of Presentation: Tsukuba International Congress Center (EPOCHAL Tsukuba), Tsukuba
• [Presentation] Control of DNAPackaging and Gene ExpressionEfficiency for Gene Delivery (2012)
  • Author(s): K. Osada, K. Kataoka
  • Organizer: 6thAnnual Symposium on Nanobiotechnology Kyoto Cell-Material Integration2012
  • Place of Presentation: KyotoUniversity, Kyoto, Japan
• [Presentation] Control of DNAPackaging and Gene ExpressionEfficiency for Gene Delivery (2012)
  • Author(s): K. Osada, K. Kataoka
  • Organizer: 1stInternational Conference on EmergingAdvanced Nanomaterials (ICEAN)
  • Place of Presentation: Mercure Hotel,Brisbane, Queensland, Australia
• [Presentation] Enhanced Gene Expression through theQuantized Folding of plasmid DNAwithin Polyplex Micelle (2012)
  • Author(s): K. Osada, K. Itaka, K. Kataoka,
  • Organizer: ACS Spring2012 National Meeting & Exposition
  • Place of Presentation: San Diego, USA
• [Presentation] ポリプレックスミセルへのpDNAパッケージング構造に与えるPEGの効果 ～ブロック/ホモ混合ポリプレックスミセルからの考察～ (2012)
  • Author(s): (長田健介)、Q. Chen、T. Tockary、石井武彦、片岡一則
  • Organizer: 第61回高分子学会年次大会
  • Place of Presentation: パシフィコ横浜、神奈川県
• [Presentation] 全身投与による膵臓がん遺伝子治療を指向したブロック/ホモポリマー混合ポリプレックスミセルの構築 (2012)
  • Author(s): (長田健介)、Q. Chen、内田智士、石井武彦、位高啓史、片岡一則
  • 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
• [Presentation] Enhanced gene expression through the quantized folding of plasmid DNA within polyplex micelle (2012)
  • Author(s): (K. Osada), K. Itaka, K. Kataoka
  • Organizer: NanoBio Seattle 2012 (The Fourth International NanoBio Conference)
  • Place of Presentation: Bell Harbor International Convention Center, Seattle, USA
• [Presentation] ポリプレックスミセルのpDNAパッケージング構造に与えるPEGの効果～PEG脱離システムからの考察～ (2012)
  • Author(s): (長田健介)、元田雄介、セオフィルス トッカリー、町谷香織、片岡一則
  • Organizer: 第61回高分子討論会
  • Place of Presentation: 名古屋工業大学、愛知
• [Presentation] 遺伝子発現効率の向上を目指したブロック/ホモポリマー混合ポリプレックスミセルの構築と全身投与による膵臓がん治療への応用 (2012)
  • Author(s): (長田健介)、Q. Chen、内田智士、石井武彦、位高啓史、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 2012 (第22回アンチセンスシンポジウム/第12回遺伝子・デリバリー研究会シンポジウム)
  • Place of Presentation: 仙台市民会館、宮城
• [Presentation] Control of DNA Packaging and Gene Expression Efficiency for Gene Delivery (2012)
  • Author(s): (K. Osada), K. Kataoka
  • Organizer: International Conference on Emerging Advanced Nanomaterial (ICEAN2012)
  • Place of Presentation: Mercure Hotel, Brisbene, Australia
  • Invited
• [Presentation] Control of DNA Packaging and Gene Expression Efficiency for Gene Delivery (2012)
  • Author(s): (K. Osada), K. Kataoka
  • Organizer: Kyoto Cell-Material Integration 2012
  • Place of Presentation: Shiran-Kaikan, Kyoto, Japan
  • Invited
• [Presentation] "Effect of PEG chain on pDNA packaging structure within polyplex micelle. -From block/homo-polymer integrated polyplex micelles-" (2012)
  • Author(s): (K. Osada), Q. Chen, T. A. Tockary,K. Itaka, K. Kataoka
  • Organizer: SPSJ International Polymer Conference
  • Place of Presentation: Kobe Convention center, Hyogo, Japan
• [Presentation] Enhanced Gene Expression through the Quantized Folding of plasmid DNA within Polyplex Micelle (2012)
  • Author(s): K.Osada, K.Itaka, K.Kataoka
  • Organizer: ACS Spring 2012 National Meeting & Exposition
  • Place of Presentation: Sandiego, USA
• [Presentation] 環状超らせん型DNAのフォールディングと遺伝子治療への展開 (2011)
  • Author(s): 長田健介、片岡一則
  • Organizer: 学術創成研究「生物ナノ構造」公開シンポジウム、招
  • Place of Presentation: 東京都
  • Year and Date: 2011-07-23
• [Presentation] プラスミドDNAの量子化折り畳み凝縮機構と遺伝子キャリアとしての機能 (2011)
  • Author(s): 長田健介、片岡一則
  • Organizer: 平成23年度日本生化学会関東支部例会、招待
  • Place of Presentation: 東京都
  • Year and Date: 2011-06-25
• [Presentation] Estimation of PEG Reduced Tethering Density of PEG-PLys based polyplex micelle (2011)
  • Author(s): Kensuke Osada, Theofilus Agrios Tockary, Kazunori Kataoka
  • Organizer: 第6回LSWシンポジウム
  • Place of Presentation: 札幌
  • Year and Date: 2011-01-07
• [Presentation] Quantized Folding of Plasmid DNA Packaged into Polyplex Micelle (2011)
  • Author(s): K.Osada, K.Kataoka
  • Organizer: The 2nd FAPS Polymer Congress (FAPS-PC2011)
  • Place of Presentation: Beijing, China
• [Presentation] Environment sensitive crosslinked polyplex micelles toward systemic gene delivery (2011)
  • Author(s): K.Osada, S.Ikeda, M.Oba, K.Miyata, K.Kataoka
  • Organizer: 第60回高分子学会年次大会
  • Place of Presentation: 大阪府
• [Presentation] ポリプレックスミセルのPEG密度とその効果 (2011)
  • Author(s): 長田健介、T.A.Tockary、片岡一則
  • Organizer: 第21回バイオ・高分子シンポジウム
  • Place of Presentation: 大阪府
• [Presentation] プラスミドDNAの凝縮機構と遺伝子キャリアとしての機能 (2011)
  • Author(s): 長田健介、位高啓史、片岡一則
  • Organizer: 第84回生化学会大会 シンポジウム、招待
  • Place of Presentation: 京都府
• [Presentation] ポリプレックスミセルにおけるPEG密度の算出と血中滞留性 (2011)
  • Author(s): 長田健介、T.A.Tockary、内田智士、位高啓史、片岡一則
  • Organizer: 第60回高分子討論会
  • Place of Presentation: 岡山県
• [Presentation] Enhance gene expression through the quantized folding of plasmid DNA within polyplex micelle (2011)
  • Author(s): K.Osada, K.Itaka, K.Kataoka
  • Organizer: The 38th International Symposium on Nucleic Acid Chemistry
  • Place of Presentation: 北海道
• [Presentation] Observation of PEG thickness ofPEG-PLys based polyplex micelle (2010)
  • Author(s): K. Osada, T. Tockary, K. Kataoka,
  • Organizer: International Chemical Congress ofPacific Basin Societies (Pacifichem2010)
  • Place of Presentation: Honolulu,USA)
• [Presentation] Quantized folding of plasmid DNApackaged into polyplex micelle. (2010)
  • Author(s): K. Osada, H. Oshima, D. Kobayashi, M.Doi, M. Enoki, Y, Yamasaki, K. Kataoka,
  • Place of Presentation: Zurich, Switzerland
• [Presentation] 環状・超らせん型DNAをどう折り畳む?～PEG-PLysブロック共重合体により誘起されるpDNAの凝縮機構～ (2010)
  • Author(s): 長田健介、片岡一則
  • Organizer: 第三回ナノバイオ若手ネットワーキングシンポジウム
  • Place of Presentation: 名古屋
• [Presentation] 長期血中滞留性を有する高分子ミセル型遺伝子キャリアの創製 (2010)
  • Author(s): 長田健介、池田宙瞳、大庭誠、宮田完二郎、片岡一則
  • Organizer: 第20回バイオ・高分子シンポジウム
  • Place of Presentation: 東京
• [Presentation] Quantized folding of plasmid DNA packaged into polyplex micelle (2010)
  • Author(s): Kensuke Osada, Hiroki Oshima, Daigo Kobayashi, Motoyoshi Doi, Manabu Enoki, Yuichi Yamasaki Kazunori Kataoka
  • Organizer: 3rd International NanoBio Conference
  • Place of Presentation: Zurich Switzerland
• [Presentation] pDNAの量子化されたフォールディング機構 (2010)
  • Author(s): 長田健介、大島弘樹、小林大悟、山崎裕一、片岡一則
  • Organizer: 第59回高分子討論会
  • Place of Presentation: 札幌
• [Presentation] Observation of PEG thickness of PEG-PLys based polyplex micelle (2010)
  • Author(s): Kensuke Osada, Theofilus Agrios Tockary, Kazunori Kataoka
  • Organizer: 2010 International Chemical Congress of Pacific Basin Societies (PACIFICHEM 2010)
  • Place of Presentation: Hawaii, USA.
• [Book] 高分子ミセル型ドラッグデリバリーシステム(DDS)-普及のインパクト ・ 課題と求められる新技術- (2013)
  • Author(s): 長田健介、片岡一則
  • Publisher: 研究開発リーダー
• [Remarks]
  • URL: http://www.bmw.t.u-tokyo.ac.jp/member/osada.html
• [Patent(Industrial Property Rights)] 核酸デリバリー用ユニット構造体 (2012)
  • Inventor(s): 片岡一則、宮田完二郎、西山伸弘、 長田健介、渡辺秀美代
  • Industrial Property Rights Holder: 国立大学法人東京大学、ナノキャリ
  • Filing Date: 2012-04-27
• [Patent(Industrial Property Rights)] 核酸デリバリー用ユニット構造体 (2012)
  • Inventor(s): 片岡一則、宮田完二郎、西山伸宏、長田健介、加藤泰己､他4名
  • Industrial Property Rights Holder: 片岡一則、宮田完二郎、西山伸宏、長田健介、加藤泰己､他4名
  • Industrial Property Rights Type: 特許
  • Industrial Property Number: 2012-102841
  • Filing Date: 2012-04-27
• [Patent(Industrial Property Rights)] 核酸送達用組成物及び担体組成物、そ (2011)
  • Inventor(s): 片岡一則、石井武彦、長田健介、陳
  • Industrial Property Rights Holder: 国立大学法人東京大学
  • Filing Date: 2011-07-11
• [Patent(Industrial Property Rights)] 核酸送達用組成物及び担体組成物、それを用いた医薬組成物、並びに核酸送達方法 (2011)
  • Inventor(s): 片岡一則、石井武彦、長田健介、陳麒先、位高啓史、内田智士
  • Industrial Property Rights Holder: 国立大学法人東京大学
  • Filing Date: 2011-07-11
  • Overseas
• [Patent(Industrial Property Rights)] ブロックコポリマー、ブロックコポリ (2010)
  • Inventor(s): 片岡一則、長田健介、岸村顕広、西
  • Industrial Property Rights Holder: 独立行政法人科学技術振興機構
  • Filing Date: 2010-05-10
• [Patent(Industrial Property Rights)] 核酸送達組成物及び担体組成物、それを用いた医薬組成物、並びに核酸送達方法 (2010)
  • Inventor(s): 片岡一則、石井武彦、長田健介、陳麒先
  • Industrial Property Rights Holder: 東京大学
  • Industrial Property Number: 2010-157296
  • Filing Date: 2010-07-09