Rational Design of Gene-Therapeutic Ribozyme

• Project/Area Number: 20550145
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Chemistry related to living body
• Research Institution: Tohoku University
• Principal Investigator: TANAKA Yoshiyuki Tohoku University, 大学院・薬学研究科, 准教授 (70333797)
• Co-Investigator(Renkei-kenkyūsha): KATO Yoshio 独立行政法人産業技術総合研究所, セルエンジニアリング研究部門, 研究員 (20415657)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2010: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2008: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 核酸 / 蛋白質 / 糖化学 / RNA / リボザイム / 遺伝子治療 / ドラッグデザイン / 三次元構造 / NMR / メカニズム / 安定同位体構造 / 安定同位体標識

Research Abstract

Gene therapy using hammerhead ribozyme were studied. It is known that hammerhead ribozyme can only cleave RNAs with UC or UA or UU sequence near the cleavage site. Based on the crystal structure of the hammerhead ribozyme, we drastically expanded the variations of the cleavable sequences, in a logical and rational manner (base-substitutions or a non-standard base-introduction into the hammerhead ribozyme). These modified ribozymes with wider cleavable sequences could be useful for a gene therapy.

Research Products

• [Journal Article] On the Role of Mercury in the Non-Covalent Stabilisation of Consecutive U-Hg^<II>-U Metal-Mediated Nucleic Acid Base Pairs : Metallophilic Attraction Enters the World of Nucleic Acids (2011)
  • Author(s): Ladislav Benda, Michal Straka, Yoshiyuki Tanaka, Vladimir Sychrovsky
  • Journal Title: Physical Chemistry Chemical Physics 13 Pages: 100-103
  • Peer Reviewed
• [Journal Article] On the Role of Mercury in the Non-Covalent Stabilisation of Consecutive U-Hg^<II>-U Metal-Mediated Nucleic Acid Base Pairs:Metallophilic Attraction Enters the World of Nucleic Acids (2011)
  • Author(s): Ladislav Benda, Michal Straka, 田中好幸, Vladimir Sychrovsky
  • Journal Title: Physical Chemistry Chemical Physics Volume: 13 Pages: 100-103
  • Peer Reviewed
• [Journal Article] Nitrogen-15 NMR Spectroscopy of Sugar Sensor with BN Interaction as a Key Regulator of Colorimetric Signals (2010)
  • Author(s): Yuya Egawa, Yoshiyuki Tanaka, Ryota Gotoh, Satoshi Niina, Yu Kojima, Naoki Shimomura, Hiroko Nakagawa, Toshinobu Seki, Jun-ichi Anzai
  • Journal Title: Chemistry Letters 39 Pages: 1188-1189
  • NAID: 120005520931
  • Peer Reviewed
• [Journal Article] DNA分子を利用した水銀除染法及び機能性核酸構造解析法の開発研究 (2010)
  • Author(s): 田中好幸
  • Journal Title: The ANNALS of Intelligent Cosmos Academic Foundation 14(依頼総説) Pages: 9-12
• [Journal Article] Nitrogen-15 NMR Spectroscopy of Sugar Sensor with BN Interaction as a Key Regulator of Colorimetric Signals (2010)
  • Author(s): 江川祐哉, 他8名(第2著者)
  • Journal Title: Chemistry Letters Volume: 39 Pages: 1188-1189
  • Peer Reviewed
• [Journal Article] DNA分子を利用した水銀除染法及び機能性核酸構造解析法の開発研究 (2010)
  • Author(s): 田中好幸
  • Journal Title: The ANNALS of Intelligent Cosmos Academic Foundation Volume: 14 Pages: 9-12
• [Journal Article] Spectroscopic analysis of the pyrimidine(6-4)pyrimidone photoproduct : Insights into the (6-4) photolyase reaction (2009)
  • Author(s): Junpei Yamamoto, Yoshiyuki Tanaka, Shigenori Iwai
  • Journal Title: Organic & Biomolecular Chemistry 7 Pages: 161-166
  • Peer Reviewed
• [Journal Article] NMR studies of HAC1 mRNA (2009)
  • Author(s): Ikumi kawahara, Kaichiro Haruta, Chojiro kojima, Yoshiyuki Tanaka
  • Journal Title: Nucleic Acids Symp. Ser. 53 Pages: 269-270
• [Journal Article] Preparations of hammerhead ribozymes for investigations of their cleavable sequences (2009)
  • Author(s): Hisaaki Tateoka, Ikumi Kawahara, Satomi Hasegawa, Kaichiro Haruta, Yoshinori Kondo, Chojiro Kojima, Yoshiyuki Tanaka
  • Journal Title: Nucleic Acids Symp. Ser. 53 Pages: 277-278
• [Journal Article] NMR studies of HAC1 mRNA (2009)
  • Author(s): 河原郁美, 春田佳一郎, 児嶋長次郎, 田中好幸
  • Journal Title: Nucleic Acids Symp.Ser. 53 Pages: 269-270
• [Journal Article] Preparations of hammerhead ribozymes for investigations of their cleavable sequences (2009)
  • Author(s): 舘岡久明, 他7名(最終著者)
  • Journal Title: Nucleic Acids Symp.Ser. 53 Pages: 277-278
• [Journal Article] Spectroscopic analysis of the pyrimidine (6-4) pyrimidone photoproduct : Insights into the (6-4) photolyase reaction (2009)
  • Author(s): 山元淳平, 田中好幸, 岩井茂憲
  • Journal Title: Organic & Biomolecular Chemistry 7 Pages: 161-166
  • Peer Reviewed
• [Journal Article] Nitrogen-15 NMR spectroscopy of N-metallated nucleic acids : Insights into ^<15>N NMR parameters and N-metal bonds (2008)
  • Author(s): 田中好幸, 小野晶
  • Journal Title: Dalton Transactions (Download Ranking Top 10 article in 1 Month) Pages: 4965-4974
  • Peer Reviewed
• [Journal Article] Specific interactions between Silver(I) Ions and Cytosine-Cytosine Pairs in DNA Duplexes (2008)
  • Author(s): Akira Ono, Shiqi Cao, Humika Togashi, Mitsuru Tashiro, Takashi Fujimoto, Tomoya Machinami, Shuji Oda, Yoko Miyake, Itaru Okamoto, Yoshiyuki Tanaka
  • Journal Title: Chemical Communications Pages: 4825-4827
  • Peer Reviewed
• [Journal Article] 新規ナノデバイス材料としてのメタロDNA分子の構造 (2008)
  • Author(s): 田中好幸, 鳥越秀峰, 小野晶
  • Journal Title: 生物物型 48(依頼総説) Pages: 119-124
  • NAID: 110006640408
• [Journal Article] Nitrogen-15 NMR spectroscopy of N-metallated nucleic acids : Insights into ^<15>N NMR parameters and N-metal bonds (2008)
  • Author(s): 田中好幸, 小野晶
  • Journal Title: Dalton Transactions Pages: 4965-4974
  • Peer Reviewed
• [Journal Article] Specific interactions between Silver (I) Ions and Cytosine-Cytosine Pairs in DNA Duplexes (2008)
  • Author(s): 小野晶(他9名)(最終著者)
  • Journal Title: Chemical Communications Pages: 4825-4827
  • Peer Reviewed
• [Journal Article] 新規ナノデバイス材料としてのメタロDNA分子の構造 (2008)
  • Author(s): 田中好幸, 鳥越秀峰, 小野晶
  • Journal Title: 生物物理 48 Pages: 119-124
  • NAID: 110006640408
  • Peer Reviewed
• [Presentation] DNA中で形成される古くて新しい塩基対(T-Hg(II)-T)とN-Hg(II)結合の性質 (2010)
  • Author(s): 田中好幸
  • Organizer: 第17回生体分子科学コロキウム
  • Place of Presentation: 茨城大学・いばらき量子ビーム研究センター(招待講演)
  • Year and Date: 2010-09-01
• [Presentation] DNA中で形成される古くて新しい塩基対(T-Hg(II)-T)とN-Hg(II)結合の性質 (2010)
  • Author(s): 田中好幸
  • Organizer: 第17回生体分子科学コロキウム
  • Place of Presentation: 東海村(茨城県)
  • Year and Date: 2010-09-01
• [Presentation] NMR分光法を用いたCatalytic RNA (hammerhead ribozyme)によるRNA鎖切断機構の解析 (2010)
  • Author(s): 田中好幸
  • Organizer: 日本化学会第4回関東支部大会
  • Place of Presentation: つくば(シンポジウム -生体高分子を機能場とする物質化学の開拓-:シンポジスト)
  • Year and Date: 2010-08-30
• [Presentation] NMR分光法を用いたCatalytic RNA (hammerhead ribozyme)によるRNA鎖切断機構の解析 (2010)
  • Author(s): 田中好幸
  • Organizer: 日本化学会第4回関東支部大会シンポジウム -生体高分子を機能場とする物質化学の開拓-
  • Place of Presentation: つくば市
  • Year and Date: 2010-08-30
• [Presentation] Nitrogen-15 NMR Chemical Shift as a Physicochemical Probe of Key Residues in Catalytic RNAs (2010)
  • Author(s): Yoshiyuki Tanaka, Masato Kato, YoshiyukiMatsuda, Vladimir Sychrovsky
  • Organizer: 10th HFSP Awardees Annual Meeting
  • Place of Presentation: ケララ州(インド)(HFSP Grant受賞者招待)
• [Presentation] Nitrogen-15 NMR Chemical Shift as a Physicochemical Probe of Key Residues in Catalytic RNAs (2010)
  • Author(s): 田中好幸
  • Organizer: 10th HFSP Awardees Annual Meeting
  • Place of Presentation: トリバンドラム,インド
• [Presentation] Detection of metalion-interactions with DNA/RNA with NMR spectroscopy (2009)
  • Author(s): 田中好幸
  • Organizer: 第47回日本生物物理学会
  • Place of Presentation: 徳島(シンポジウム-New Developments on Molecular Spectroscopy of Biometals by Young Researchers-:シンポジスト)
  • Year and Date: 2009-10-30
• [Presentation] 核酸-金属相互作用のNMR分光法による検出(シンポジウム依頼講演) (2009)
  • Author(s): 田中好幸
  • Organizer: 日本生物物理学会第47回年会
  • Place of Presentation: 徳島
  • Year and Date: 2009-10-30
• [Presentation] NMR分光法による核酸-金属複合体の機能・構造解析 (2009)
  • Author(s): 田中好幸
  • Organizer: 平成21年度学術講演会(日本薬学会東北支部主催)
  • Place of Presentation: 仙台(招待講演)
  • Year and Date: 2009-07-11
• [Presentation] NMR分光法による核酸-金属複合体の機能・構造解析(依頼講演) (2009)
  • Author(s): 田中好幸
  • Organizer: 平成21年度 学術講演会(日本薬学会東北支部主催)
  • Place of Presentation: 仙台
  • Year and Date: 2009-07-11
• [Presentation] Sample Preparation of a Catalytic RNA (Hammerhead Ribozyme) for Spectroscopy and Crystallography (2009)
  • Author(s): Yoshiyuki Tanaka, Masato Kato, Yoshiyuki Matsuda, Vladimir Sychrovsky
  • Organizer: 9th HFSP Awardees Annual Meeting
  • Place of Presentation: 東京(日本)(HFSP Grant受賞者招待)
• [Presentation] 長鎖RNA分子の部位特異的安定同位体標識法の開発 (2008)
  • Author(s): 春田佳一郎(他3名)(最終著者)
  • Organizer: 日本化学会第89春季年会
  • Place of Presentation: 千葉
  • Year and Date: 2008-03-28
• [Book] Metal Complexes - DNA Interactions(Structural Studies on Mercury^<II>-mediated T-T Base-pair with NMR Spectroscopy (Chapter 16), In Nick Hadjiliadis and Einar Sletten Eds.)(John Wiley & Sons) (2009)
  • Author(s): Yoshiyuki Tanaka, Akira Ono
  • Publisher: West Sussex, UK
• [Book] Metal Complexes-DNA Interactions (2009)
  • Author(s): 田中好幸, 小野晶
  • Publisher: John Wiley & Sons, West Sussex, UK
• [Remarks] ホームページ等
• [Remarks]
  • URL: http://www.pharm.tohoku.ac.jp/~henkan/lab/tanaka/tanaka.html
• [Remarks]
  • URL: http://www.pharm.tohoku.ac.jp/~henkan/lab/tanaka/tanaka.html
• [Remarks]
  • URL: http://www.pharm.tohoku.ac.jp/~henkan/lab/tanaka/tanaka.html