写真a

KAWAKAMI Junji

Position

Professor

Research Field

Life Science / Pharmaceutical analytical chemistry and physicochemistry, Nanotechnology/Materials / Chemistry and chemical methodology of biomolecules, Nanotechnology/Materials / Bio chemistry, Life Science / Molecular biology, Life Science / Structural biochemistry

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Graduating School 【 display / non-display

  • Graduate School of Hokkaido University   Pharmaceutical Sciences   Graduated

    1991.4 - 1994.3

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  • Graduate School of Osaka University   Pharmaceutical Sciences   Graduated

    1989.4 - 1991.3

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  • Osaka University   Faculty of Pharmaceutical Science   Graduated

    1985.4 - 1989.3

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Graduate School 【 display / non-display

  • Hokkaido University   Graduate School, Division of Pharmaceutical Sciences   Doctor's Course   Completed

    1991.4 - 1994.3

  • Osaka University   Graduate School, Division of Pharmaceutical Sciences   Master's Course   Completed

    1989.4 - 1991.3

Studying abroad experiences 【 display / non-display

  • 2001.3
    -
    2002.3

    Yale University   Visiting Scholar

Campus Career 【 display / non-display

  • KONAN UNIVERSITY   Department of Nanobiochemistry, FIRST   Professor

    2009.4

  •   理工学部 機能分子化学科   准教授

    2007.4 - 2009.3

  •   理工学部 機能分子化学科   助教授

    2005.4 - 2007.3

  •   理工学部 機能分子化学科   講師

    2001.4 - 2005.3

  •   理学部 化学科   講師

    1996.4 - 2001.3

External Career 【 display / non-display

  • Professor, Department of Nanobiochemistry, FIRST, Konan University

    2009

  • 甲南大学 フロンティアサイエンス学部 教授

    2009

  • Associate Professor, Faculty of Science and Engineering, Konan University

    2005 - 2009

  • Visiting Fellow, Yale University

    2001 - 2002

  • YALE大学 客員研究員

    2001 - 2002

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Professional Memberships 【 display / non-display

  • NUCLEIC ACIDS THERAPEUTICS SOCIETY OF JAPAN

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  • Nucleic Acids Therapeutics Society of Japan

    2015.4

  • The Japan Society of Nucleic Acids Chemistry

    2017.11

  • THE MOLECULAR BIOLOGY SOCIETY OF JAPAN

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  • American Association for the Advancement of Science

    1996.4

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Papers 【 display / non-display

  • Separation of the diastereomers of phosphorothioated siRNAs by anion-exchange chromatography under non-denaturing conditions Reviewed International journal

    Hiroyuki Togawa, Takashi Okubo, Kazuki Horiuchi, Takao Yamaguchi, Elisa Tomita-Sudo, Tomoka Akita, Junji Kawakami, Satoshi Obika

    Journal of Chromatography A   1721   464847   2024.4

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    Joint Work

    In recent years, several small interfering RNA (siRNA) therapeutics have been approved, and most of them are phosphorothioate (PS)-modified for improving nuclease resistance. This chemical modification induces chirality in the phosphorus atom, leading to the formation of diastereomers. Recent studies have revealed that Sp and Rp configurations of PS modifications of siRNAs have different biological properties, such as nuclease resistance and RNA-induced silencing complex (RISC) loading. These results highlight the importance of determining diastereomeric distribution in quality control. Although various analytical approaches have been used to separate diastereomers (mainly single-stranded oligonucleotides), it becomes more difficult to separate all of them as the number of PS modifications increases. Despite siRNA exhibits efficacy in the double-stranded form, few reports have examined the separation of diastereomers in the double-stranded form. In this study, we investigated the applicability of non-denaturing anion-exchange chromatography (AEX) for the separation of PS-modified siRNA diastereomers. Separation of the four isomers of the two PS bonds tended to improve in the double-stranded form compared to the single-stranded form. In addition, the effects of the analytical conditions and PS-modified position on the separation were evaluated. Moreover, the elution order of the Sp and Rp configurations was confirmed, and the steric difference between them, i.e., the direction of the anionic sulfur atom, appeared to be important for the separation mechanism in non-denaturing AEX. Consequently, all 16 peak tops of the four PS modifications were detected in one sequence, and approximately 30 peak tops were detected out of 64 isomers of six PS bonds, indicating that non-denaturing AEX is a useful technique for the quality control of PS-modified siRNA therapeutics.

    DOI: 10.1016/j.chroma.2024.464847

  • Sequencing of Morpholino Antisense Oligonucleotides Using Electron Capture Dissociation Mass Spectrometry Reviewed International journal

    Kaoru Karasawa, Eva Duchoslav, Lyle Burton, Junji Kawakami, Takashi Baba

    Analytical Chemistry   95 ( 44 )   16352 - 16358   2023.10

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    Joint Work

    We report the first sequencing of morpholino antisense oligonucleotides (phosphorodiamidate morpholino oligomers, PMOs) using electron capture dissociation (ECD) mass spectrometry. In this research, we found dissociation of the backbone of 18- to 25-mer PMOs to produce d and z ions as the major ions, and 100% cleavage coverage (sequence coverage) was obtained with these ions. This is a critical contrast with beam-type collision-induced dissociation, which dominantly induces base loss, so it is difficult to obtain sequence information. The results showed that an electron beam energy (typically 15 eV) can be used universally for PMOs with different sequences, lengths, and charge states so that no detailed optimization is required for multiprecursor targeting liquid chromatography coupled with tandem mass spectrometry measurements. We also confirmed that the ECD reaction speed was compatible with the high-performance liquid chromatography time scale. Finally, we demonstrated a liquid chromatography electron capture dissociation tandem mass spectrometry workflow to survey the modification sites of the emulated PMO impurities.

    DOI: 10.1021/acs.analchem.3c03621

    DOI: 10.1021/acs.analchem.3c03621

    Other Link: https://doi.org/10.1021/acs.analchem.3c03621

  • Mitochondrial Dynamics of Bcl-2 Family Proteins during 17-β-Estradiol-Induced Apoptosis Correlate with the Malignancy of Endometrial Cancer Cells Reviewed

    Takahiro Yaguchi, Misaki Kameno, Hirofumi Taira, and Junji Kawakami

    Biochemstry   62 ( 21 )   3041 - 3049   2023.10

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  • Comparison of Analysis Data of Model Oligonucleotide Therapeutics Obtained with Different Types of Liquid Chromatograph- Mass Spectrometers Reviewed

    Kenji Hirose, Tokuyuki Yoshida, Maki Terasaki, Hiroshi Sezaki, Kaoru Karasawa, Noriyuki Iwasaki, Kentaro Takahara, Naomi Takiguchi, Mitsuaki Sekiguchi, Hirokazu Nankai, Emi Saito, Hideaki Sato, Takashi Osawa, Takao Yamaguchi, Kosuke Ito, Junji Kawakami, Satoshi Obika, and Takao Inoue

    Pharmaceutical and Medical Device Regulatory Science   54   439 - 454   2023.10

  • Not all 2',4'-bridged modifications stabilize DNA/RNA duplexes Reviewed

    Tomoka Akita, Elisa Tomita-Sudo, Shin Itoh, Nae Sakimoto, Takeshi Masuda, Akifumi Nakamura, Yoshiyuki Onishi, Makoto Koizumi Junji Kawakami

    Nucleosides, Nucleotides & Nucleic Acids   2023.3

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    Joint Work

    2’,4’-Bridged modifications such as 2’-O,4’-C-methylene-bridged nucleotides (LNAs) and 2’-O,4’-C-ethylene-bridged nucleotides (ENAs) provide high binding affinity for duplex formation. Stabilization by the introduction of the bridged nucleic acids is considered to be due to pre-organization. In this study, we found that the introduction of 2’,4’-C-bridged 2’-deoxynucleotides (CRNs; Conformationally Restricted Nucleotides) into DNA/RNA duplexes leads to destabilization, as opposed to the previously accepted notion that 2’,4’-bridged modifications always lead to stabilization.

    Other Link: https://www.tandfonline.com/doi/full/10.1080/15257770.2023.2232414

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Books and Other Publications 【 display / non-display

  • 核酸医薬 モダリティ・合成・分析・DDSの最新動向

    冨田恵麗沙、秋田智香、川上純司( Role: Contributor ,  核酸医薬の不純物と管理)

    NTS  2024.4  ( ISBN:978-4-86043-886-9

  • 不純物の分析法と化学物質の取り扱い

    騰川博之、大久保貴史、野中祐美、山口卓男、小比賀聡、川上純司( Role: Contributor ,  核酸医薬品の不純物の分析)

    技術情報協会   2024.1  ( ISBN:978-4-86104-998-9

  • 核酸医薬品のCMC管理戦略 −品質評価・不純物管理−

    冨田恵麗沙, 秋田智香, 川上純司( Role: Contributor ,  核酸医薬品と核酸化学)

    サイエンス&テクノロジー  2022.9  ( ISBN:9784864282925

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  • 核酸科学ハンドブック

    川上純司( Role: Contributor ,  アンチセンス核酸のメカニズム)

    講談社  2020.12  ( ISBN:9784065207864

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  • 医薬品開発における中分子領域(核酸医薬・ペプチド医薬)の開発戦略

    川上 純司(アンチセンス核酸医薬の作用機序)

    情報機構  2019.10 

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Review Papers (Misc) 【 display / non-display

  • 核酸医療の基礎知識 修飾核酸 Invited

    秋田 智香、冨田 恵麗沙、川上 純司

    月刊 臨床神経科学   41 ( 5 )   639 - 642   2023.5

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    Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • 日本発の核酸医薬を世界に向けて

    川上純司

    SCAS NEWS   2023-1   1 - 2   2023

  • LC/MSを使用したオリゴ核酸の不純物分析

    瀬崎浩史、内藤厚子、林明生、川上純司、井上貴雄、山口卓男、小比賀聡

    Medical Science Digest   49 ( 14 )   780 - 782   2023

  • 製造委託の際に知っておきたい核酸医薬の特性ー品質と安全性評価面を中心に  Invited

    川上 純司

    Pharm Tech Japan    38 ( 12 )   2017 - 2022   2022.9

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    Publishing type:Article, review, commentary, editorial, etc. (scientific journal)  

  • 核酸医薬の化学 総論 −修飾核酸と機能評価

    秋田智香、川上純司

    実験医学   39 ( 17 )   2716 - 2722   2021

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Presentations 【 display / non-display

  • The development of continuous purification process for oligonucleotides purification and its potential benefits

    Cheng-Linn Lee, Mayuko Mouri, Kengo Kashio, Kiyotaka Takimoto, Junji Kawakami, Takao Inoue, Satoshi Obika, Eigo Muto

    XXV International Round Table on Nucleosides, Nucleotides and Nucleic Acids (IRT2024)  2024.9 

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    Event date: 2024.9

  • Stability and structural analysis of DNA/RNA heteroduplexes containing a bulge

    Tomoka Akita, Taiichi Sakamoto, Elisa Tomita-Sudo, Renshin Sano, Nae Sakimoto, Junji Kawakami

    XXV International Round Table on Nucleosides, Nucleotides and Nucleic Acids (IRT2024)  2024.9 

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    Event date: 2024.9

  • p53機能欠損が惹起する異常な核小体ストレス応答の解明

    取井猛流、本間美和子、川上純司、三好大輔、川内敬子

    2024年度文部科学省学術変革領域研究先端モデル動物支援プラットフォーム若手支援技術講習会  2024.8 

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    Event date: 2024.8

  • rRNA量の低下が引き起こす核小体構造変化におけるG-quadruplexの働き

    取井猛流、月生雅也、平田宏聡、川上純司、村嶋貴之、三好大輔、川内敬子

    2024年度文部科学省学術変革領域研究先端モデル動物支援プラットフォーム若手支援技術講習会  2024.8 

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    Event date: 2024.8

  • 連続クロマトグラフィー(MCSGP)を用いたオリゴ核酸の精製(第二報)

    加塩健悟、毛利真裕子、瀧本清貴、川上純司、井上貴雄、小比賀聡、武藤英吾

    日本核酸医薬学会第9回年会  2024.7 

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    Event date: 2024.7

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Grant-in-Aid for Scientific Research 【 display / non-display

  • ヘアピンループDNA/RNAを認識するモデルペプチドの速度論的機能評価

    2004.4 - 2006.3

    JSPS Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists(B)

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    ヘアピンループDNA/RNAを認識するモデルペプチドの速度論的機能評価
    領域・整理
    ・課題番号
    4706
    7305
    16750150

  • ヘアピンループDNA/RNAを認識するモデルペプチドの速度論的機能評価

    2004.4 - 2006.3

    JSPS Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists(B)

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    ヘアピンループDNA/RNAを認識するモデルペプチドの速度論的機能評価
    領域・整理
    ・課題番号
    4706
    7305
    16750150

  • ヘアピンループDNA/RNAを認識するモデルペプチドの速度論的機能評価

    2004.4 - 2006.3

    JSPS Grants-in-Aid for Scientific Research Grant-in-Aid for Young Scientists(B)

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    ヘアピンループDNA/RNAを認識するモデルペプチドの速度論的機能評価
    領域・整理
    ・課題番号
    4706
    7305
    16750150

Preferred joint research theme 【 display / non-display

  • 新規機能性核酸(アプタマー等)の取得

  • リアルタイムPCR等を使用した遺伝子の定量解析

  • 人為的遺伝子発現調節(翻訳)

 

Committee Memberships 【 display / non-display

  • 2015.4   日本核酸医薬学会  評議員、幹事、事務局

  • 2016.9   日本核酸化学会  評議員

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  • 2004.4 - 2017.3   高分子学会  バイオ・高分子研究会 運営委員

  • 2015.12   日本核酸医薬学会  事務局長

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  • 2015.4   日本核酸医薬学会  評議員

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Social Activities 【 display / non-display

  • 出張模擬講義

    2014.12

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    毒学 - 薬学へのいざない/兵庫県立舞子高等学校

  • 模擬講義

    2014.12

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    毒学/兵庫大学附属須磨ノ浦高等学校

  • サイエンスパートナーシッププロジェクト

    2014.8

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    自然科学入門講座「身近な生活から最先端の遺伝子研究について学ぶ」- 遺伝子鑑定/兵庫県立星陵高等学校

  • etc

    2014.3

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    遺伝子鑑定の精度・信憑性/兵庫県警察本部 刑事部

  • 模擬講義

    2013.12

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    くすりの科学/須磨ノ浦女子高等学校

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