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Establishment of chemical RNA editing method for genetic code resoration therapy

Research Project

Project/Area Number 25290072
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Medical genome science
Research InstitutionJapan Advanced Institute of Science and Technology

Principal Investigator

Tsukahara Toshifumi  北陸先端科学技術大学院大学, 先端科学技術研究科, 教授 (60207339)

Co-Investigator(Kenkyū-buntansha) 鈴木 仁  北陸先端科学技術大学院大学, マテリアルサイエンス研究科, 助教 (00447690)
藤本 健造  北陸先端科学技術大学院大学, マテリアルサイエンス研究科, 教授 (90293894)
Co-Investigator(Renkei-kenkyūsha) Takada Shin'ichi  国立研究開発法人国立精神・神経医療研究センター, 神経研究所, 所長 (90171644)
Project Period (FY) 2013-04-01 – 2017-03-31
Project Status Completed (Fiscal Year 2016)
Budget Amount *help
¥18,460,000 (Direct Cost: ¥14,200,000、Indirect Cost: ¥4,260,000)
Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2013: ¥8,060,000 (Direct Cost: ¥6,200,000、Indirect Cost: ¥1,860,000)
Keywords疾患治療 / 点変異 / RNA editing / 脱アミノ化 / 蛍光タンパク質 / 遺伝コード修復 / RFLP / 恒常的発現細胞 / 恒常的発言細胞株 / 恒常的発現細胞株 / RNA Editing / 恒常発現細胞株
Outline of Final Research Achievements

Photochemical site-specific deamination was performed toward BFP-mRNA, by using oligodeoxynucleotides,ODNs, for inducing deamination. The base substitution by artificial RNA editing was confirmed by RT-PCR-RFLP analysis and fluorescence of in-vitro-translated proteins. Moreover, the mRNA sample was sequenced after photochemical RNA editing treatments, and confirmed that there was no mutation occurred except the target-site. We also investigated the ODN design that could induce efficient deamination. The ODN with complementary sequence length of 14 bases and hairpin length of 9 bases showed the highest photochemical RNA editing efficiency at 12.4%. This result suggests that the photochemical RNA editing is applicable as a theraputic method for genetic diseases.

Report

(5 results)
  • 2016 Annual Research Report   Final Research Report ( PDF )
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • 2013 Annual Research Report
  • Research Products

    (17 results)

All 2017 2016 2015 2014 2013

All Journal Article (12 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 12 results,  Open Access: 11 results,  Acknowledgement Compliant: 11 results) Presentation (3 results) (of which Int'l Joint Research: 1 results) Book (1 results) Patent(Industrial Property Rights) (1 results)

  • [Journal Article] Neuron-specific splicing2017

    • Author(s)
      Nor Hakimah Ab Hakim, Burhanuddin Yeop Majlis, Hitoshi Suzuki, Toshifumi Tsukahara,
    • Journal Title

      BioScience Trends

      Volume: 11 Issue: 1 Pages: 16-22

    • DOI

      10.5582/bst.2016.01169

    • NAID

      130005466226

    • ISSN
      1881-7815, 1881-7823
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] C-to-U Editing and Site-Directed RNA Editing for Correction of Genetic Mutations.2017

    • Author(s)
      Vu Thi Luyen and Toshifumi Tsukahara
    • Journal Title

      Bioscience Trends, inpress.

      Volume: 11

    • NAID

      130005853626

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Chemical RNA Editing for Genetic Restoration: The Relationship between the Structure and Deamination Efficiency of Carboxyvinyldeoxyuridine Oligodeoxynucleotides2016

    • Author(s)
      Vu Thi Luyen, Nguyen Thi Kim Thanh, Md Thoufic Anam Azad, Hitoshi Suzuki, and Toshifumi Tsukahara
    • Journal Title

      Chemical Biology & Drug Design

      Volume: 87 Issue: 4 Pages: 583-593

    • DOI

      10.1111/cbdd.12693

    • Related Report
      2016 Annual Research Report 2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Endogenous Multiple Exon Skipping and Back-Splicing at the DMD Mutation Hotspot2016

    • Author(s)
      Hitoshi Suzuki, Yoshitsugu Aoki, Toshiki Kameyama, Takashi Saito, Satoru Masuda, Jun Tanihata, Tetsuya Nagata, Akila Mayeda, Shin’ichi Takeda, Toshifumi Tsukahara
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 17 Issue: 10 Pages: 1722-1722

    • DOI

      10.3390/ijms17101722

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Expression Analysis of Fox-2 Alternative Isoforms during Neuronal Differentiation2016

    • Author(s)
      Nor Hakimah Ab Hakim, Burhanuddin Yeop Majlis, Hitoshi Suzuki and Toshifumi Tsukahara
    • Journal Title

      Int’l Journal of Advances in Chemical Engg., & Biological Sciences

      Volume: 3 Issue: 1 Pages: 102-104

    • DOI

      10.15242/ijacebs.iae0516407

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Changing Blue Fluorescent Protein to Green Fluorescent Protein Using Chemical RNA Editing as a Novel Strategy in Genetic Restoration2015

    • Author(s)
      Luyen T. Vu, Thanh T. K. Nguyen, Shafiul Alam, Takashi Sakamoto, Kenzo Fujimoto, Hitoshi Suzuki and Toshifumi Tsukahara
    • Journal Title

      Chemical Biology & Drug Design

      Volume: 86 Issue: 5 Pages: 1242-1252

    • DOI

      10.1111/cbdd.12592

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Critical Effect of Base Pairing of Target Pyrimidine on the Inter-strand Photo-cross-linking of DNA via 3-Cyanovinylcarbazole Nucleoside2015

    • Author(s)
      Takashi Sakamoto, Minako Ooe, Kenzo Fujimoto
    • Journal Title

      Bioconjugate Chemistry

      Volume: 26 Issue: 8 Pages: 1475-1478

    • DOI

      10.1021/acs.bioconjchem.5b00352

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Photo-cross-linking using trifluorothymidine and 3-cyanovinylcarbazole induced large shifted 19F MR signal2015

    • Author(s)
      Shigetaka Nakamura, Kenzo Fujimoto
    • Journal Title

      Chemical Communications

      Volume: 51 Issue: 59 Pages: 11765-11768

    • DOI

      10.1039/c5cc02972d

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Computational extraction of a neural molecular network through alternative splicing2014

    • Author(s)
      Alam S, Phan HT, Okazaki M, Takagi M, Kawahara K, Tsukahara T, Suzuki H
    • Journal Title

      BMC Res. Notes

      Volume: 7 Issue: 1 Pages: 934-934

    • DOI

      10.1186/1756-0500-7-934

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Alternative splicing regulation of APP exon 7 by RBFox proteins2014

    • Author(s)
      Alam S, Suzuki H, Tsukahara T
    • Journal Title

      Neurochem. Int.

      Volume: 78 Pages: 7-17

    • DOI

      10.1016/j.neuint.2014.08.001

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] A View of Pre-mRNA Splicing from RNase R Resistant RNAs2014

    • Author(s)
      Suzuki H, Tsukahara T
    • Journal Title

      Int. J. Mol. Sci.

      Volume: 15 Issue: 6 Pages: 9331-9342

    • DOI

      10.3390/ijms15069331

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Nested introns in an intron : Evidence of multi-step splicing in a large intron of the human dystrophin pre-mRNA.2013

    • Author(s)
      Suzuki, H., Kameyama, T., Ohe, K. Tsukahara, T., Mayeda, A.
    • Journal Title

      FEBS Letters

      Volume: 587 Issue: 6 Pages: 555-561

    • DOI

      10.1016/j.febslet.2013.01.057

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Presentation] Study of adenosine deaminase acting on RNA (ADAR) isoforms towards genetic code restoration2016

    • Author(s)
      Md Thoufic Anam Azad, Hitoshi Suzuki, Toshifumi Tsukahara
    • Organizer
      アメリカ細胞生物学会年会
    • Place of Presentation
      サンフランシスコ(アメリカ合衆国)
    • Year and Date
      2016-12-03
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Site-directed RNA editing approach by MS2 and adenosine deaminase acting on RNA (ADAR)2016

    • Author(s)
      Md Thoufic Anam Azad, Hitoshi Suzuki, Toshifumi Tsukahara
    • Organizer
      日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] Possibility of Genetic Code Restoration by Chemical RNA Editing2013

    • Author(s)
      Toshifumi Tsukahara
    • Organizer
      BIT's Biopharmaceutical Summit-2013
    • Place of Presentation
      Frankfurt, Germany
    • Related Report
      2013 Annual Research Report
  • [Book] New Developments on Alternative Splicing Research2013

    • Author(s)
      Hitoshi Suzuki and Toshifumi Tsukahara
    • Total Pages
      181
    • Publisher
      Nova Science Publishers
    • Related Report
      2013 Annual Research Report
  • [Patent(Industrial Property Rights)] 塩基置換手段をスクリーニングする方法2015

    • Inventor(s)
      塚原俊文、藤本健造
    • Industrial Property Rights Holder
      北陸先端科学技術大学院大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2015-085414
    • Filing Date
      2015-04-17
    • Related Report
      2015 Annual Research Report

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Published: 2013-05-21   Modified: 2019-07-29  

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