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Development of a novel RNAi medicine based on shRNA expression mini-plasmid

Research Project

Project/Area Number 24390027
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Drug development chemistry
Research InstitutionThe University of Tokushima

Principal Investigator

MINAKAWA Noriaki  徳島大学, ヘルスバイオサイエンス研究部, 教授 (40209820)

Co-Investigator(Kenkyū-buntansha) ISHIDA Tstsuhiro  徳島大学, 大学院ヘルスバイオサイエンス研究部, 教授 (50325271)
Project Period (FY) 2012-04-01 – 2015-03-31
Project Status Completed (Fiscal Year 2014)
Budget Amount *help
¥18,850,000 (Direct Cost: ¥14,500,000、Indirect Cost: ¥4,350,000)
Fiscal Year 2014: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2013: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2012: ¥9,880,000 (Direct Cost: ¥7,600,000、Indirect Cost: ¥2,280,000)
KeywordsRNAi創薬 / 4'-チオDNA / PCR / 非天然塩基対 / クリックケミストリー / 免疫応答
Outline of Final Research Achievements

In this study, I aim at a development of novel RNAi medicine based on shRNA expression mini-gene. As a result, I succeeded to prepare the mini-gene via PCR amplification using 2’-deoxy-4’-thionucleoside triphosphates (dSNTPs). In addition, I also developed a practical method to cyclize the resulting mini-gene.
The mini-gene showed potent RNAi activity both in vitro and in vivo. In addition, innate immune responses such as type-I INF and inflammatory cytokines were hardly induced by administration of the mini-gene in vivo.

Report

(4 results)
  • 2014 Annual Research Report   Final Research Report ( PDF )
  • 2013 Annual Research Report
  • 2012 Annual Research Report
  • Research Products

    (36 results)

All 2015 2014 2013 2012

All Journal Article (9 results) (of which Peer Reviewed: 9 results,  Open Access: 1 results,  Acknowledgement Compliant: 2 results) Presentation (27 results) (of which Invited: 1 results)

  • [Journal Article] First synthesis of fully modified 4'-selenoRNA and 2'-OMe-4'-selenoRNA based on the mechanistic considerations of an unexpected strand break.2014

    • Author(s)
      Tarashima, N.; Hayashi, K.; Terasaki, M.; Tanike, H.; Inagaki, Y.; Fukuda, Y.; Furukawa, K.; Matsuda, A.; Minakawa,
    • Journal Title

      Org. Lett.

      Volume: 16 Issue: 18 Pages: 4710-4713

    • DOI

      10.1021/ol502077h

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Development of a New Dumbbell-Shaped Decoy DNA Using a Combination of the Unnatural Base Pair ImON:NaNO and a CuAAC Reaction2014

    • Author(s)
      Yosuke Higuchi, Kazuhiro Furukawa, Tadashi Miyazawa, and Noriaki Minakawa
    • Journal Title

      Bioconjugate Chem.

      Volume: 25 Issue: 7 Pages: 1360-1369

    • DOI

      10.1021/bc500225r

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] PCR Amplification of 4'-ThioDNA Using 2'-Deoxy-4'-thionucleoside 5'-Triphosphates.2013

    • Author(s)
      Kojima, T. ; Furukawa, K. ; Maruyama, H. ; Inoue, N. ; Tarashima, N. ; Matsuda, A. ; Minakawa, N.
    • Journal Title

      ACS Synth. Biol.

      Volume: 2 Issue: 9 Pages: 529-536

    • DOI

      10.1021/sb400074w

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Synthesis of a novel 1,2-dithianenucleoside via Pummerer-like reaction, followed by Vorbruggen glycosylation between 1,2-dithiane derivative and uracil.2013

    • Author(s)
      Miyazawa, T. ; Umezaki. K. ; Tarashima, N. ; Furukawa, K. : Ooi, T. ; Minakawa, N.
    • Journal Title

      Chem. Commun.

      Volume: 49 Issue: 71 Pages: 7851-7853

    • DOI

      10.1039/c3cc44848g

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Gene suppression via U1 small nuclear RNA interference (U1i) machinery using oligonucleotides containing 2'-modified-4'-thionudeosides.2013

    • Author(s)
      Kukuchi, Y. ; Yamazaki, N. ; Tarashima, N. ; Furukawa, K. : Takiguchi, Y. ; Itoh, K. ; Minakawa, N.
    • Journal Title

      Bioorg. Med. Chem.

      Volume: 21 Issue: 17 Pages: 5292-5296

    • DOI

      10.1016/j.bmc.2013.06.023

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] In vitro potimization of 2'-Ome-4'-thioribonucleoside-modified anti-microRNA oligonucleotides and its targeting delivery to mouse liver using a liposomal nanoparticle2013

    • Author(s)
      Mayumi Takahashi, Naoki Yamada, Hiroto Hatakeyama, Manami Murata, Yusuke Sato, Noriaki Minakawa, Hideyoshi Harashima, Akira Matsuda
    • Journal Title

      Nucleic Acids Res.

      Volume: 41 Issue: 22 Pages: 10659-10667

    • DOI

      10.1093/nar/gkt823

    • Related Report
      2013 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 4'・チオDNAを用いたRNA創薬2013

    • Author(s)
      南川典昭
    • Journal Title

      YAKUGAKU ZASSHI

      Volume: 133 Pages: 53-60

    • NAID

      130003361879

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] A practical post-modification synthesis of oligodeoxynucleotides containing 4,7-diaminoimidazo[5',4':4,5]pyrido[2,3-d]pyrimidine nucleoside2012

    • Author(s)
      Noriko Tarashima, Yosuke Higuchi, Yasuo Komatsu, and Noriaki Minakawa
    • Journal Title

      Bioorg. Med. Chem

      Volume: 20 Issue: 24 Pages: 7095-7100

    • DOI

      10.1016/j.bmc.2012.10.035

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Intracellular stability of 2'-OMe-4'-thioribonucleoside modified siRNA leads to long-term RNAi effect2012

    • Author(s)
      Mayumi Takahashi
    • Journal Title

      Nucleic Acids Research

      Volume: (in press) Issue: 12 Pages: 5787-5793

    • DOI

      10.1093/nar/gks204

    • Related Report
      2012 Annual Research Report
    • Peer Reviewed
  • [Presentation] Intelligent RNA expression device (iRed) を利用した 新規遺伝子発現抑制法の開発2015

    • Author(s)
      田良島 典子, 小島 孝允, 金城 望, 古川 和寛, 安藤 英紀, 石田 竜弘, 南川 典昭
    • Organizer
      第95回日本化学会
    • Place of Presentation
      日本大学 船橋キャンパス(千葉県船橋市)
    • Year and Date
      2015-03-26 – 2015-03-29
    • Related Report
      2014 Annual Research Report
  • [Presentation] Intelligent RNA expressing device (iRed) を利用した核酸創薬の新手法2014

    • Author(s)
      田良島典子,小島孝光,金城望,古川和寛、安藤英紀,石田竜弘,南川典昭
    • Organizer
      第32回メディシナルケミストリーシンポジウム
    • Place of Presentation
      神戸国際会議場(兵庫県神戸市)
    • Year and Date
      2014-11-26 – 2014-11-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] A new dumbbell-shaped decoy DNA targeting NF-kB with the unnatural base pair ImON:NaNO2014

    • Author(s)
      Kazuhiro Furukawa, Yosuke Higuchi, Tadashi Miyazawa, Noriaki Minakawa
    • Organizer
      10th Annual meeting of the oligonucleotide therapeutics society
    • Place of Presentation
      San Diego (USA)
    • Year and Date
      2014-10-12 – 2014-10-15
    • Related Report
      2014 Annual Research Report
  • [Presentation] 4’-セレノ核酸の化学 ―4’-セレノ核酸は4’-チオ核酸を超えることが出来るか?―2014

    • Author(s)
      南川典昭
    • Organizer
      アンチセンス・遺伝子・デリバリーシンポジウム2014
    • Place of Presentation
      東京医科歯科大学(東京都文京区)
    • Year and Date
      2014-09-08 – 2014-09-09
    • Related Report
      2014 Annual Research Report
    • Invited
  • [Presentation] Enzymatic synthesis of 4’-selenoDNA2014

    • Author(s)
      Noriko Tarashima, Tatsuya Sumitomo, Kazuhiro Furukawa, Noriaki Minakawa
    • Organizer
      XXI Round Table on Nucleosides, Nucleotides and Nucleic Acids
    • Place of Presentation
      Poznan(Poland)
    • Year and Date
      2014-08-24 – 2014-08-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] HOW TO PREPARE 4’-SELENORNA?2014

    • Author(s)
      Noriaki Minakawa, Noriko Tarashima, Koya Hayashi, Maki Terasaki, Hirotsugu Taniike, Yusuke Inagaki, Shinji Fukuda, Kazuhiro Furukawa and Akira Matsuda
    • Organizer
      XXI Round Table on Nucleosides, Nucleotides and Nucleic Acids
    • Place of Presentation
      Poznan(Poland)
    • Year and Date
      2014-08-24 – 2014-08-28
    • Related Report
      2014 Annual Research Report
  • [Presentation] 人工塩基対ImNN:NaOOのPCR増幅とRNAi創薬への応用2014

    • Author(s)
      南川典昭
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本大学(熊本県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] クリックケミストリーを用いたRNA簡便精製法の開発2014

    • Author(s)
      南川典昭
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本大学(熊本県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 2’-デオキシ-4’-セレノピリミジンヌクレオシドの合成とDNAオリゴマーへの導入2014

    • Author(s)
      南川典昭
    • Organizer
      日本薬学会第134年会
    • Place of Presentation
      熊本大学(熊本県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 新規Im : Na塩基対のDNAポリメラーゼによる基質認識2013

    • Author(s)
      南川典昭
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2013-03-28
    • Related Report
      2012 Annual Research Report
  • [Presentation] Huisgen反応を利用したImO^N : NaN^o塩基対を含む環状DNAの合成2013

    • Author(s)
      南川典昭
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2013-03-28
    • Related Report
      2012 Annual Research Report
  • [Presentation] 新規含硫ヌクレオシド誘導体の合成2013

    • Author(s)
      南川典昭
    • Organizer
      日本薬学会第133年会
    • Place of Presentation
      パシフィコ横浜(神奈川県)
    • Year and Date
      2013-03-28
    • Related Report
      2012 Annual Research Report
  • [Presentation] A novel approach of gene suppression using an intelligent shRNA expressing device (iRed)2013

    • Author(s)
      Noriaki Minakawa
    • Organizer
      9th Annual Meeting of the Oligonucleotide Therapeutics Society
    • Place of Presentation
      Royal Continental Hotel (Italy)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 新規1, 2-ジチアンヌクレオシドの合成と性質2013

    • Author(s)
      南川典昭
    • Organizer
      第52回日本薬学会中国四国支部学術大会
    • Place of Presentation
      松山大学(愛媛県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 2'-デオキシ-4'-セレノピリミジンヌクレオシドの合成2013

    • Author(s)
      南川典昭
    • Organizer
      第52回日本薬学会中国四国支部学術大会
    • Place of Presentation
      松山大学(愛媛県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Enzymatic incorporation of unnatural ImNN:NaOO base pair consisting of four hydrogen bonds2013

    • Author(s)
      南川典昭
    • Organizer
      第40回国際核酸化学シンポジウム
    • Place of Presentation
      神奈川大学(神奈川県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Synthesis of circular decoy DNA containing unnatural base pair ImON:NaNO by CuAAC reaction2013

    • Author(s)
      南川典昭
    • Organizer
      第40回国際核酸化学シンポジウム
    • Place of Presentation
      神奈川大学(神奈川県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Consideration of insufficient yield in oligonucleotide synthesis containing 4’-selenonucleosides2013

    • Author(s)
      南川典昭
    • Organizer
      第40回国際核酸化学シンポジウム
    • Place of Presentation
      神奈川大学(神奈川県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] ALLOSTERIC CONTROL OF DNA-HYDROLYZING DEOXYRIBOZYME BY SHORT OLIGONUCLEOTIDES2013

    • Author(s)
      南川典昭
    • Organizer
      第40回国際核酸化学シンポジウム
    • Place of Presentation
      神奈川大学(神奈川県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 改変U1 snRNAによる遺伝子発現抑制効果の検討2013

    • Author(s)
      南川典昭
    • Organizer
      第23回アンチセンスシンポジウム
    • Place of Presentation
      徳島大学(徳島県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] 複数の改変U1 snRNAを用いた遺伝子発現抑制2013

    • Author(s)
      南川典昭
    • Organizer
      第23回アンチセンスシンポジウム
    • Place of Presentation
      徳島大学(徳島県)
    • Related Report
      2013 Annual Research Report
  • [Presentation] Chemistry & Biology of 4'-thioDNA2012

    • Author(s)
      Noriaki Minakawa
    • Organizer
      Memorial Seminar of International Academic Exchange between Dongguk University & The University of Tokushima
    • Place of Presentation
      Dongguk University (Korea)(招待講演)
    • Year and Date
      2012-12-21
    • Related Report
      2012 Annual Research Report
  • [Presentation] Gene silencing by 2' -modified-4' -thio oligonucleotides via U1i machinery2012

    • Author(s)
      Noriaki Minakawa
    • Organizer
      第39回国際核酸化学シンポジウム
    • Place of Presentation
      名古屋大学(愛知県)
    • Year and Date
      2012-11-15
    • Related Report
      2012 Annual Research Report
  • [Presentation] 核酸医薬の現状と将来2012

    • Author(s)
      南川典昭
    • Organizer
      プロセス化学東四国フォーラムセミナー
    • Place of Presentation
      徳島文理大学(徳島県)(招待講演)
    • Year and Date
      2012-09-29
    • Related Report
      2012 Annual Research Report
  • [Presentation] Huisgen反応を利用したImO^N : NaN^o塩基対を含む環状DNAの合成研究2012

    • Author(s)
      南川典昭
    • Organizer
      アンチセンス・遺伝子・デリバリーシンポジウム2012
    • Place of Presentation
      仙台市民会館(宮城県)
    • Year and Date
      2012-09-25
    • Related Report
      2012 Annual Research Report
  • [Presentation] 4'-チオDNAを利用した新規RNAi法の開発2012

    • Author(s)
      南川典昭
    • Organizer
      第6回バイオ関連化学シンポジウム
    • Place of Presentation
      北海道大学(北海道)
    • Year and Date
      2012-09-07
    • Related Report
      2012 Annual Research Report
  • [Presentation] 化学修飾DNAを利用するRNAi創薬の新展開2012

    • Author(s)
      南川典昭
    • Organizer
      第19回ファーマサイエンスフォーラム
    • Place of Presentation
      北海道大学(北海道)(招待講演)
    • Year and Date
      2012-07-25
    • Related Report
      2012 Annual Research Report

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Published: 2012-04-24   Modified: 2019-07-29  

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