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2005 Fiscal Year Final Research Report Summary

Creation of extra base pairs for the development of novel functional nucleic acids

Research Project

Project/Area Number 15350097
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Chemistry related to living body
Research InstitutionThe University of Tokyo

Principal Investigator

HIRANO Ichiro  The University of Tokyo, Research Center for Advanced Science and Technology, Specially Appointed Professor, 先端科学技術研究センター, 科学技術振興特任教員(特任教授) (50173216)

Co-Investigator(Kenkyū-buntansha) MITSUI Tsuneo  The University of Tokyo, Research Center for Advanced Science and Technology, Specially Appointed Associate, 先端科学技術研究センター, 科学技術振興特任教員(特任助手) (60345155)
IKEDA Shuji  The University of Tokyo, Research Center for Advanced Science and Technology, Specially Appointed Associate, 先端科学技術研究センター, 科学技術振興特任教員(特任助手) (80336320)
Project Period (FY) 2003 – 2005
Keywordsunnatural base pairs / artificial nucleic acids / artificial proteins / replication / transcription / translation
Research Abstract

The expansion of the genetic alphabet by the addition of an artificial, extra base pair allows for the site-specific, enzymatic incorporation of functional nucleotide analogs into RNA by transcription. Toward the novel biotechnology of the artificial base pair system, we have studied the creation of the extra base pairs that function in replication, transcription, and translation.
We already developed an extra base pair (s-y) that functions in transcription and translation, enabling the site-specific incorporations of nucleotide analogs into RNAs and of amino acid analogs into proteins. However, the selectivity of the s-y pair in replication is not as high as that in transcription, and the s-y pair cannot be practically used in replication, such as PCR amplification and in vivo experiments.
Here, we present several extra base pairs that exhibit unique selectivity in polymerase reactions. Among them, the Ds-Pa pair functions with extremely high complementary selectivity in replication and transcription. DNA fragments containing the Ds-Pa pair can be amplified by PCR, and both substrates of Ds and Pa can be site-specifically incorporated into RNA by T7 RNA polymerase. Thus, this extra base pair system expands the genetic alphabet, providing a novel DNA/RNA-based biotechnology for creating nucleic acids bearing extra components at desired positions.

  • Research Products

    (50 results)

All 2006 2005 2004 2003 Other

All Journal Article (39 results) Book (5 results) Patent(Industrial Property Rights) (6 results)

  • [Journal Article] Development of unnatural base pair systems-toward the creation of novel functional RNA molecules.2006

    • Author(s)
      I.Hirao
    • Journal Title

      Functional non-coding RNA

      Pages: 255

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Re-creation of the central dogma.2006

    • Author(s)
      H.Murakami, H.Suga, I.Hirao
    • Journal Title

      Bionics 3

      Pages: 92

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Inhibition of the signal transduction and cancer therapy by aptamers.2006

    • Author(s)
      I.Hirao
    • Journal Title

      RNA and drug discovery

      Pages: 228

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Development of novel functional biopolymers by unnatural base pair systems.2006

    • Author(s)
      I.Hirao
    • Journal Title

      Nikkei-science 5

      Pages: 140

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Site-specific fluorescent labeling of RNA molecules by specific transcription using unnatural base pairs.2005

    • Author(s)
      R.Kawai, M.Kimoto, S.Ikeda, T.Mitsui, M.Endo, S.Yokoyama, I.Hirao
    • Journal Title

      J. Am. Chem. Soc. 127

      Pages: 17286-17295

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] An efficient unnatural base pair for a base-pair-expanded transcription system.2005

    • Author(s)
      T.Mitsui, M.Kimoto, Y.Harada, S.Yokoyama, I.Hirao
    • Journal Title

      J. Am. Chem. Soc 127

      Pages: 8652-8658

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Site-specific biotinylation of RNA molecules by transcription using unnatural base pairs.2005

    • Author(s)
      K.Moriyama, M.kimoto, T.Mitsui, S.Yokoyama, I.Hirao
    • Journal Title

      Nucleic Acids Res. 33

      Pages: e129-

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] In vitro セレクション-標的タンパク質に結合するRNAアプタマーの作成-2005

    • Author(s)
      平尾 一郎
    • Journal Title

      生命化学研究レター 19

      Pages: 21-25

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] DNA/RNA アプタマー-その作成から臨床応用まで-2005

    • Author(s)
      平尾 一郎
    • Journal Title

      医薬ジャーナル 41

      Pages: 2015-2022

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Site-specific fluorescent labeling of RNA molecules by specific transcription using unnatural base pairs.2005

    • Author(s)
      R.Kawai, M.Kimoto, S.Ikeda, T.Mitsui, M.Endo, S.Yokoyama, J.Hirao
    • Journal Title

      J.Am.Chem.Soc. 127

      Pages: 17286-17295

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] An efficient unnatural base pair for a base-pair-expanded transcription system.2005

    • Author(s)
      T.Mitsui, M.Kimoto, Y.Harada, S.Yokoyama, I.Hirao
    • Journal Title

      J.Am.Chem.Soc. 127

      Pages: 8652-8658

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Site-specific biotinylation of RNA molecules by transcription using unnatural base pairs.2005

    • Author(s)
      K.Moriyama, M.Kimoto, T.Mitsui, S.Yokoyama, I.Hirao
    • Journal Title

      Nucleic Acids Res. 33

      Pages: e129

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] In vitro selection-Preparation of RNA aptamers that bind to target proteins.2005

    • Author(s)
      I.Hirao
    • Journal Title

      Forum of Biomol.Chem.Lett. 19

      Pages: 21-25

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] DNA/RNA aptamers : from preparation to pharmaceutical applications.2005

    • Author(s)
      I.Hirao
    • Journal Title

      Iyaku J. 41

      Pages: 2015-2022

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A two-unnatural-base-pair system toward the expansion of the genetic code.2004

    • Author(s)
      I.Hirao, Y.Harada, M.Kimoto, T.Mitsui, T.Fujiwara, S.Yokoyama
    • Journal Title

      J. Am. Chem. Soc. 126

      Pages: 13298-13305

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Unnatural base pairs between 2- and 6-substituted purines and 2- oxo(1H)pyridine for expansion of the genetic alphabet.2004

    • Author(s)
      I.Hirao, T.Fujiwara, M.Kimoto, S.Yokoyama
    • Journal Title

      Bioorg. Me. Chem. Lett. 14

      Pages: 4887-4890

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A quantitative, non-radioactive single-nucleotide insertion assay for analysis of DNA replication fidelity by using an automated DNA sequencer.2004

    • Author(s)
      K.Michiko, S.Yokoyama, I.Hirao
    • Journal Title

      Biotechnol. Lett. 26

      Pages: 999-1005

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Unnatural base pairs mediate the site-specific incorporation of an unnatural hydrophobic component into RNA transcripts.2004

    • Author(s)
      M.Endo, T.Mitsui, T.Okuni, M.Kimoto, I.Hirao, S.Yokoyama
    • Journal Title

      Bioorg. Med. Chem. Lett. 14

      Pages: 2593-2596

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Site-specific incorporation of a photo-crosslinking component into RNA by T7 transcription mediated by unnatural base pairs.2004

    • Author(s)
      M.kimoto, M.Endo, T.Mitsui, T.Okuni, I.Hirao, S.Yokoyama
    • Journal Title

      Chem. Biol. 11

      Pages: 47-55

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] A two-unnatural-base-pair system toward the expansion of the genetic code.2004

    • Author(s)
      I.Hirao, Y.Harada, M.Kimoto, T.Mitsui, T.Fujiwara, S.Yokoyama
    • Journal Title

      J.Am.Chem.Soc. 126

      Pages: 13298-13305

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Unnatural base pairs between 2- and 6-substituted purines and 2-oxo(1H)pyridine for expansion of the genetic alphabet.2004

    • Author(s)
      I.Hirao, T.Fujiwara, M.Kimoto, S.Yokoyama
    • Journal Title

      Bioorg.Med.Chem.Lett. 14

      Pages: 4887-4890

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] A quantitative, non-radioactive single-nucleotide insertion assay for analysis of DNA replication fidelity by using an automated DNA sequencer.2004

    • Author(s)
      M.Kimoto, S.Yokoyama, I.Hirao
    • Journal Title

      Biotechnol.Lett. 26

      Pages: 999-1005

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Unnatural base pairs mediate the site-specific incorporation of an unnatural hydrophobic component into RNA transcripts.2004

    • Author(s)
      M.Endo, T.Mitsui, T.Okuni, M.Kimoto, I.Hirao, S.Yokoyama
    • Journal Title

      Bioorg.Med.Chem.Lett. 14

      Pages: 2593-2596

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Site-specific incorporation of a photo-crosslinking component into RNA by T7 transcription mediated by unnatural base pairs.2004

    • Author(s)
      M.Kimoto, M.Endo, T.Mitsui, T.Okuni, I.Hirao, S.Yokoyama
    • Journal Title

      Chem.Biol. 11

      Pages: 47-55

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] An unnatural hydrophobic base, 4-propynylpyrrole-2-carbaldehyde, as an efficient pairing partner of 9-methylimidazo[(4,5)-b]pyridine.2003

    • Author(s)
      T.Mitsui, M.Kimoto, A.Sato, S.Yokoyama, I.Hirao
    • Journal Title

      Bioorg. Med. Chem. Lett. 13

      Pages: 4515-4518

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] An unnatural hydrophobic base pair with shape complementarity between pyrrole-2-carbaldehyde and 9-methylimidazo[(4,5)-b]pyridine.2003

    • Author(s)
      T.Mitsui, A.Kitamura, M.Kimoto, T.To, A.Sato, I.Hirao, S.Yokoyama
    • Journal Title

      J. Am. Chem. Soc. 125

      Pages: 5298-5307

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 新規遺伝子の人工創製2003

    • Author(s)
      平尾 一郎, 横山 茂之
    • Journal Title

      蛋白質・核酸・酵素 48

      Pages: 1496-1502

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 新しい医薬 : 核酸アプタマー2003

    • Author(s)
      平尾 一郎, 木本 路子
    • Journal Title

      バイオマテリアル・生体材料 21

      Pages: 270-277

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] "宇宙人"の遺伝子を作る2003

    • Author(s)
      平尾 一郎
    • Journal Title

      化学と教育 51

      Pages: 410-413

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] An unnatural hydrophobic base, 4-propynylpyrrole-2-carbaldehyde, as an efficient pairing partner of 9-methylimidazo[(4, 5)-b]pyridine.2003

    • Author(s)
      M.Mitsui, M.Kimoto, A.Sato, S.Yokoyama, I.Hirao
    • Journal Title

      Bioorg.Med.Chem.Lett. 13

      Pages: 4515-4518

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] An unnatural hydrophobic base pair with shape complementarity between pyrrole-2-carbaldehyde and 9-methylimidazo[(4, 5)-b]pyridine.2003

    • Author(s)
      M.Mitsui, A.Kitamura, M.Kimoto, T.To, A.Sato, I.Hirao, S.Yokoyama
    • Journal Title

      J.Am.Chem.Soc. 125

      Pages: 5298-5307

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Creation of artificial genes.2003

    • Author(s)
      I.Hirao, S.Yokoyama
    • Journal Title

      Tanpakushitsu Kakusan Koso 48

      Pages: 1496-1502

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Novel therapeutic and diagnostic reagents : nucleic acid aptamers.2003

    • Author(s)
      I.Hirao, M.Kimoto
    • Journal Title

      J.Jpn.Soc.Biomaterials 21

      Pages: 270-277

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Creation of extra-terrestrial genetic materials.2003

    • Author(s)
      I.Hirao
    • Journal Title

      Chem.Edu. 51

      Pages: 410-413

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Unnatural base pairs capable of being recognized by polymerases.2003

    • Author(s)
      I.Hirao
    • Journal Title

      Genome Chemistry

      Pages: 240

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Placing extra components into RNA by specific transcription using unnatural base pair systems.

    • Author(s)
      I.Hirao
    • Journal Title

      BioTechniques (in press)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] 人工塩基対による遺伝情報の拡張

    • Author(s)
      平尾 一郎
    • Journal Title

      蛋白質・核酸・酸素 (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Placing extra components into RNA by specific transcription using unnatural base pair systems.

    • Author(s)
      I.Hirao
    • Journal Title

      Bio Texhniques (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] Expansion of the genetic information by using artificial base pairs.

    • Author(s)
      I.Hirao
    • Journal Title

      Tanpakushitsu Kakusan Koso (in press)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Book] 機能性 Non-coding RNA2006

    • Author(s)
      平尾 一郎
    • Total Pages
      255
    • Publisher
      人工塩基対システムの開発 : 機能性RNAの創製を目指して
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] バイオニクス2006

    • Author(s)
      村上 裕, 菅 裕明, 平尾 一郎
    • Total Pages
      92
    • Publisher
      セントラルドグマを作り変える
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] RNAと創薬2006

    • Author(s)
      平尾 一郎
    • Total Pages
      228
    • Publisher
      アプタマーによるシグナル伝達の阻害と制癌戦略
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] 日経サイエンス2005

    • Author(s)
      平尾 一郎
    • Total Pages
      140
    • Publisher
      汎用性の高い人口塩基対を応用した高機能バイオポリマーの開発
    • Description
      「研究成果報告書概要(和文)」より
  • [Book] ゲノムケミストリー2003

    • Author(s)
      平尾 一郎
    • Total Pages
      240
    • Publisher
      ポリメラーゼ認識能をもつ人工塩基対
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] 核酸の複製の方法及び新規人工塩基対2005

    • Inventor(s)
      平尾, 横山
    • Industrial Property Rights Holder
      理化学研究所, 東京大学
    • Industrial Property Number
      特願2005-356883
    • Filing Date
      2005-12-09
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] 新規人工塩基対及びその利用2005

    • Inventor(s)
      平尾, 横山
    • Industrial Property Rights Holder
      理化学研究所, 東京大学
    • Industrial Property Number
      特願2005-226492
    • Filing Date
      2005-08-04
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] イミダゾピリジン誘導体2005

    • Inventor(s)
      平尾, 横山
    • Industrial Property Rights Holder
      理化学研究所
    • Industrial Property Number
      特願2005-012585
    • Filing Date
      2005-01-20
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] 新規なヌクレオチド若しくはヌクレオチド誘導体及びその利用2005

    • Inventor(s)
      平尾, 横山
    • Industrial Property Rights Holder
      理化学研究所, 東京大学
    • Industrial Property Number
      国際出願:PCT/JP2005/20435
    • Filing Date
      2005-11-08
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] 抗がん剤2005

    • Inventor(s)
      平尾, 横山
    • Industrial Property Rights Holder
      理化学研究所, 東京大学
    • Patent Publication Number
      特開 2005-232079
    • Filing Date
      2005-09-02
    • Description
      「研究成果報告書概要(和文)」より
  • [Patent(Industrial Property Rights)] 非天然型塩基を有するヌクレオシド又はヌクレオチド及びその利用2005

    • Inventor(s)
      平尾, 横山
    • Industrial Property Rights Holder
      理化学研究所, 東京大学
    • Industrial Property Number
      国際公開:WO 2005/026,187
    • Filing Date
      2005-03-24
    • Description
      「研究成果報告書概要(和文)」より

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Published: 2007-12-13  

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