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Development and application of novel in-vivo-RNA restoration method by using enzyme-RNA complexes.

Research Project

Project/Area Number 17H02204
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Biomolecular chemistry
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)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥17,160,000 (Direct Cost: ¥13,200,000、Indirect Cost: ¥3,960,000)
Fiscal Year 2019: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2017: ¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
KeywordsRNA editing / 人工酵素複合体 / 遺伝コード修復 / ADAR1 / APOBEC1 / 脱アミノ化 / Macularマウス / デアミナーゼ / APOBEC/AID / guide RNA / Cas13a / 標的RNA分解 / RNAエディティング / APOBEC/AIDファミリー / アミノ基付加反応 / MS2 / AID / 生体機能利用 / 生体分子 / 核酸 / 酵素 / バイオテクノロジー
Outline of Final Research Achievements

To treat diseases caused by point mutations in the gene, we have developed a site-specific repairing method for genetic codes of the mutated RNAs, and succeeded in developing an artificial enzyme complex that catalyzes A⇒I (G) or C⇒U conversions in cells. The enzyme complex was able to act specifically on the mutated points of RNA by guide RNAs complementary to the target RNAs, and was able to repair about 40% of the mutated RNAs in cells. We also successfully repaired the genetic code of mutated P-type ATPase RNA in primary cultured fibroblasts derived from macular mice as a disease model, confirming the restoration of cytochrome C oxidase activity, whose activity is almost undetectable in macular mice.

Academic Significance and Societal Importance of the Research Achievements

遺伝子変異の修復法としてゲノム編集技術が脚光をあびているが、患者体内で変異したDNAだけを正確に改変出来る技術は確立されておらず、現状では体外でゲノム編集し正しく改変された細胞を体内に戻す方法でしか疾患を治療できない。本研究は遺伝性疾患の多くを占める点変異を原因とする疾患への治療法として変異したRNAを細胞内で修復するという新しい治療法の開発研究である。我々は本研究において細胞内で約40%の変異RNAを修復することに成功し、またモデルマウスを対象に実際の疾患にも適用可能であることを示した。本研究が提案するRNAの遺伝コード修復は様々な遺伝性疾患の治療法に新しいパラダイムを提供する。

Report

(4 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • 2017 Annual Research Report
  • Research Products

    (27 results)

All 2020 2019 2018 2017 Other

All Int'l Joint Research (2 results) Journal Article (9 results) (of which Int'l Joint Research: 4 results,  Peer Reviewed: 9 results,  Open Access: 5 results) Presentation (15 results) (of which Int'l Joint Research: 7 results,  Invited: 3 results) Patent(Industrial Property Rights) (1 results)

  • [Int'l Joint Research] Catholic University of Leuven(ベルギー)

    • Related Report
      2017 Annual Research Report
  • [Int'l Joint Research] University of Rajshahi(バングラデシュ)

    • Related Report
      2017 Annual Research Report
  • [Journal Article] The m6A Methyltransferase METTL3 Contributes to Transforming Growth Factor-beta-induced Epithelial-Mesenchymal Transition of Lung Cancer Cells Through the Regulation of JUNB2020

    • Author(s)
      Wanna-udom Sasithorn、Terashima Minoru、Hanbing Lyu、Ishimura Akihiko、Takahisa Takino、Matomo Sakari、Toshifumi Tsukahara、Suzuki Takeshi
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 524 Issue: 1 Pages: 150-155

    • DOI

      10.1016/j.bbrc.2020.01.042

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Analysis of tissue-specific RNA editing events of genes involved in RNA editing in Arabidopsis thaliana2019

    • Author(s)
      Umme Qulsum, Md. Thoufic Anam Azad, Toshifumi Tsukahara
    • Journal Title

      Jornal of Plant Biology

      Volume: 62 Issue: 5 Pages: 351-358

    • DOI

      10.1007/s12374-018-0452-5

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Comparative Activity of Adenosine Deaminase Acting on RNA (ADARs) Isoforms for Correction of Genetic Code in Gene Therapy,2019

    • Author(s)
      Md. Thoufic Anam Azad, Umme Qulsum, Toshifumi Tsukahara
    • Journal Title

      Current Gene Therapy

      Volume: 19 Issue: 1 Pages: 31-39

    • DOI

      10.2174/1566523218666181114122116

    • Related Report
      2019 Annual Research Report 2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Genetic code restoration by artificial RNA editing of Ochre stop codon with ADAR1 deaminase2019

    • Author(s)
      Sonali Bhakta, Md Thoufic Anam Azad, Toshifumi Tsukahara
    • Journal Title

      Protein Engneering , Design and Selection

      Volume: -

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Tissue-specific alternative splicing of pentatricopeptide repeat (PPR) family genes in <i>Arabidopsis thaliana </i>2018

    • Author(s)
      Umme Qulsum and Toshifumi Tsukahara,
    • Journal Title

      BioScience Trends

      Volume: 12 Issue: 6 Pages: 569-579

    • DOI

      10.5582/bst.2018.01178

    • NAID

      130007575204

    • ISSN
      1881-7815, 1881-7823
    • Year and Date
      2018-12-31
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genotyping of single nucleotide polymorphisms using the SNP-RFLP method2018

    • Author(s)
      Saifullah and Toshifumi Tsukahara
    • Journal Title

      BioScience Trends

      Volume: 12 Issue: 3 Pages: 240-246

    • DOI

      10.5582/bst.2018.01102

    • NAID

      130007405694

    • ISSN
      1881-7815, 1881-7823
    • Year and Date
      2018-06-30
    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Single nucleotide recognition using a probes-on-carrier DNA chip.2018

    • Author(s)
      Saifullah, Satoshi Fuke, Hiroshi Nagasawa and Toshifumi Tsukahara
    • Journal Title

      BioTechniques

      Volume: 66 Issue: 2 Pages: 73-78

    • DOI

      10.2144/btn-2018-0088

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] C-to-U editing and site-directed RNA editing for the correction of genetic mutations2017

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

      BioScience Trends

      Volume: 11 Issue: 3 Pages: 243-253

    • DOI

      10.5582/bst.2017.01049

    • NAID

      130005853626

    • ISSN
      1881-7815, 1881-7823
    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Site-directed RNA editing by adenosine deaminase acting on RNA for correction of the genetic code in gene therapy2017

    • Author(s)
      Azad Md T A、Bhakta S、Tsukahara T
    • Journal Title

      Gene Therapy

      Volume: 24 Issue: 12 Pages: 779-786

    • DOI

      10.1038/gt.2017.90

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Genetic Code Rest oration by Using Artificial RNA Editing for G to A mutated mRNAs2019

    • Author(s)
      Toshifumi Tsukahara, Sonali Bhakta, Md. Thoufic Anam Azad
    • Organizer
      World Congress of Molecular & Cell Biology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Artificial RNA Editing in (BFP) Blue Fluorescence Protein (Derivative of GFP) by Using APOBEC1 Deaminase for Restoration of Genetic Code2019

    • Author(s)
      Sonali Bhakta, Md. Thoufic Anam Azad, Toshifumi Tsukahara
    • Organizer
      World Congress of Molecular & Cell Biology
    • Related Report
      2019 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Application of CRISPR-Cas13 machinery to disease treatment2019

    • Author(s)
      Saifullah, Matomo Sakari, Toshifumi Tsukahara
    • Organizer
      日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Genetic code restoration by using APOBEC1 artificial cytidine deaminase2019

    • Author(s)
      Sonali Bhakta and Toshifumi Tsukahara
    • Organizer
      日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Investigation of tissue-specific alternative splicing of Organelle RNA Recognition Motif(ORRM) family genes in Arabidopsis thaliana2019

    • Author(s)
      John MW Munene and Toshifumi Tsukahara,
    • Organizer
      日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] RNAメチル基転移酵素METTL3の転写共役機構2019

    • Author(s)
      盛 真友、塚原 俊文
    • Organizer
      Hokuriku RNA Club 2019
    • Related Report
      2018 Annual Research Report
  • [Presentation] Artificial RNA editing enzymes for RNA restoration in vivo2018

    • Author(s)
      Toshifumi Tsukahara, Md Thoufic Anam Azad, Sonalo Bhakta, Matomo Sakari
    • Organizer
      alaysia-Japan Joint International Conference 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Site-Directed RNA Editing of Mutated RNAs by Artificial Enzymes2018

    • Author(s)
      Toshifumi Tsukahara, Md Thoufic Anam Azad, Sonalo Bhakta, Matomo Sakari
    • Organizer
      BIT's 9th World Gene Convention-2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Artificial RNA editing in Ochre (TAA) Stop codon for restoration of genetic code by using ADAR1 deaminase2018

    • Author(s)
      Sonali Bhakta, MD Thoufic Anam Azad and Toshifumi Tsukahra
    • Organizer
      JAIST World Conference 2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 3.Analysis of tissue-specific alternative splicing of P-subfamily PPR genes in Arabidopsis thaliana.2018

    • Author(s)
      Umme Qulsum, Toshifumi Tsukahara
    • Organizer
      JAIST World Conference 2018
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Comparative activity of adenosine deaminase acting on RNA (ADARs) isoforms for correction of genetic code in gene therapy.2017

    • Author(s)
      Md Thoufic Anam Azad, Hitoshi Suzuki, Toshifumi Tsukahara
    • Organizer
      日本RNA学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Genetic code restoration by ADAR1 in Ochre (TAA) stop codon.2017

    • Author(s)
      Sonali Bhakta, Md Thoufic Anam Azad, Matomo Sakari and Toshifumi Tsukahra.
    • Organizer
      日本RNA学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 1.Alternative Splicing of RNA Editing Pentatricopeptide Repeat (PPR) Family Gene in Arabidopsis thaliana2017

    • Author(s)
      Umme Qulsum, John Munene, Toshifumi Tsukahara
    • Organizer
      日本RNA学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 2.Tissue-specific Alternative Splicing of RNA Editing Related Family Genes in Arabidopsis thaliana2017

    • Author(s)
      Umme Qulsum, Toshifumi Tsukahara
    • Organizer
      日本分子生物学会年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Artificial enzyme system for treatment of genetic disorders.2017

    • Author(s)
      Md Thoufic Anam Azad, Sonali Bhakta, Toshifumi Tsukahra
    • Organizer
      Smart knowledge/ smart information/ smart materials workshop 2017
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Patent(Industrial Property Rights)] タンパク質を生合成させる方法および未成熟終止コドンの修飾方法2019

    • Inventor(s)
      塚原 俊文、盛 真友、田中 龍太
    • 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
      2019-018379
    • Filing Date
      2019
    • Related Report
      2018 Annual Research Report

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Published: 2017-04-28   Modified: 2021-02-19  

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