2026
■論文
Theoretical calculation of the amounts of nucleotide deletion impurities in oligonucleotides
Yasunori Uchida, Tokuyuki Yoshida, Emi Saito, Hirokazu Nankai, Kaoru Karasawa, Chie Inagaki, Noriyuki Iwasaki, Daisuke Higo, Kentaro Takahara, Takashi Osawa, Takao Yamaguchi, Kosuke Ito, Junji Kawakami, Satoshi Obika, Takao Inoue
Int. J. Pharm.
Yasunori Uchida, Tokuyuki Yoshida, Emi Saito, Hirokazu Nankai, Kaoru Karasawa, Chie Inagaki, Noriyuki Iwasaki, Daisuke Higo, Kentaro Takahara, Takashi Osawa, Takao Yamaguchi, Kosuke Ito, Junji Kawakami, Satoshi Obika, Takao Inoue
Int. J. Pharm.
■総説
■著書
2025
■論文
Separation of deaminated impurities from the desired oligonucleotides using supercritical fluid chromatography
Momoka Hayashida, Risa Suzuki, Shinnosuke Horie, Junichi Masuda, Takao Yamaguchi, Satoshi Obika
J. Chromatogr. A 1744 465731
Effect of Chemical Modification on The Exon Skipping Activity of Heteroduplex Oligonucleotides
T. Shimo, J. Hasegawa, K. Yoshioka, Y. Nakatsuji, K. Aso, K. Tachibana, T. Nagata, T. Yokota, S. Obika
Mol. Ther. Nucleic Acids 36 102468
Synthesis and structural analysis of dinucleotides containing 2′,3′-trans-bridged nucleic acids with trans-5,6- or 5,7-fused ring skeleton
T. Osawa, R. Nakanishi, K. Uda, S. Muramoto, S. Obika
Commun. Chem 8 87
Antisense oligonucleotide targeting nicotinamide N-methyltransferase exhibits antitumor effects
T. Hara, S. Meng, Y. Kasahara, T. Osawa, D. Motooka, H. Sato, Y. Arao, Y. Saito, K. Inoue, Y. Hamano, Y. Doki, H. Eguchi, S. Obika, H. Ishii
Mol. Ther. Nucleic Acids 36(2) 102548
Effects of acid-mediated deamination of cytidine and 5-methylcytidine on solid-phase synthesis of oligonucleotides
Y. Isono, C. Karasugi, T. Akisawa, T. Osawa, Q. Ren, M. Tatsuno, F. Ito, T. Inoue, J. Kawakami, S. Obika, M. Shinoda
Tetrahedron 185 134840
Phthalimide: a potential warhead for switchable and bioorthogonal conjugation
Kosuke Chiba, Takumi Yoshida, Kana Okada, Minory Ishikawa, Yuichi Hashimoto, Satoshi Obika, Takao Yamaguchi
Chem. Commun. 61 13417–13420
Unraveling and controlling late-onset neurotoxicity of antisense oligonucleotides through strategic chemical modifications
Takayuki Kuroda, Kotaro Yoshioka, Su Su Lei Mon, Maho Katsuyama, Kumiko Sato, Eriko Isogai, Kie Yoshida-Tanaka, Rintaro Iwata-Hara, Takao Yamaguchi, Satoshi Obika, Takanori Yokota
Mol. Ther. Nucleic Acids 36 102692
Development of a Synthetic Lethality-Based Combination Therapy Using LIG1 and PARP Inhibitors for Prostate Cancer
Masaru Tani, Koji Hatano, Yu Ishizuya, Toshiki Oka, Tomohiro Kanaki, Shunsuke Inoguchi, Akihiro Yoshimura, Yuki Horibe, Yutong Liu, Sassi Nesrine, Yohei Okuda, Akinaru Yamamoto, Toshihiro Uemura, Gaku Yamamichi, Takuji Hayashi, Yoshiyuki Yamamoto, Taigo Kato, Atsunari Kawashima, Takao Yamaguchi, Satoshi Obika, Kosuke Yusa, Norio Nonomura, Keisuke Nimura
Cancer Science 116 3403–3416
Rational design of a covalent ACE2 decoy receptor that broadly neutralizes SARS-CoV-2 variants
Nobumasa Hino, Risa Takada, Kyosuke Suzuki, Nagisa Tokunoh, Tatsuya Karaki, Kazumasa Ohtake, Haruna Ogami, Takafumi Nishiura, Kenji Ishimoto, Tomohito Tsukamoto, Yukio Ago, Yoshiaki Okada, Toru Okamoto, Chikako Ono, Yoshiharu Matsuura, Satoshi Obika, Kensaku Sakamoto, Yasuo Yoshioka, Shinsaku Nakagawa
Protein Science 34 e70306
Cycloalkane incorporation into the 2′,4′-bridge of locked nucleic acid: enhancing nuclease stability, reducing phosphorothioate modifications, and lowering hepatotoxicity in antisense oligonucleotides
Takao Yamaguchi, Hibiki Komine, Takaya Sugiura, Riku Kumagai, Tokuyuki Yoshida, Kiyomi Sasaki, Taisuke Nakayama, Haruhiko Kamada, Takao Inoue, Satoshi Obika
JACS Au 5 5111–5120
Hydrophilic additives enhancing electrospray ionization of oligonucleotides in hexafluoro-2-propanol-free reversed-phase ion-pair liquid chromatography/mass spectrometry
Takashi Miyazaki, Natsuyo Asano, Satoshi Yamaki, Takao Yamaguchi, Satoshi Obika
J. Chromatogr. A 1765 466485
Development of synthetic routes to 2′-O,4′-C-spirocyclopentylene-bridged nucleic acids: thymidine, guanosine, and adenosine
Riku Kumagai, Riko Yamada, Takao Yamaguchi, Satoshi Obika
Chem. Eur. J. 31 e02995
Sequence-dependent RNA cleavage by the 8–17 DNAzyme: Identification of preferred tetranucleotide motifs
Satoko Nakajima, Shuhei Miyakawa, Shu Ohno, Haruki Ikemoto, Rikuto Maruyama, Kosuke Chiba, Ryota Suginakaa, Chihiro Oda, Yuuya Kasahara, Kaori Fukuzawa, Satoshi Obika, Takao Yamaguchi
Bioorg. Med. Chem. 134 118520
Regulation of Duplex Formation in Response to pH and Comple-mentary RNA: Development of Oligonucleotides Modified with S-Methylthioimidate-Bridged Nucleic Acid and Evaluation of Their Function
T. Osawa, K. Miyata, S. Ito, K. Uda, S. Obika
ACS Omega
Momoka Hayashida, Risa Suzuki, Shinnosuke Horie, Junichi Masuda, Takao Yamaguchi, Satoshi Obika
J. Chromatogr. A 1744 465731
Effect of Chemical Modification on The Exon Skipping Activity of Heteroduplex Oligonucleotides
T. Shimo, J. Hasegawa, K. Yoshioka, Y. Nakatsuji, K. Aso, K. Tachibana, T. Nagata, T. Yokota, S. Obika
Mol. Ther. Nucleic Acids 36 102468
Synthesis and structural analysis of dinucleotides containing 2′,3′-trans-bridged nucleic acids with trans-5,6- or 5,7-fused ring skeleton
T. Osawa, R. Nakanishi, K. Uda, S. Muramoto, S. Obika
Commun. Chem 8 87
Antisense oligonucleotide targeting nicotinamide N-methyltransferase exhibits antitumor effects
T. Hara, S. Meng, Y. Kasahara, T. Osawa, D. Motooka, H. Sato, Y. Arao, Y. Saito, K. Inoue, Y. Hamano, Y. Doki, H. Eguchi, S. Obika, H. Ishii
Mol. Ther. Nucleic Acids 36(2) 102548
Effects of acid-mediated deamination of cytidine and 5-methylcytidine on solid-phase synthesis of oligonucleotides
Y. Isono, C. Karasugi, T. Akisawa, T. Osawa, Q. Ren, M. Tatsuno, F. Ito, T. Inoue, J. Kawakami, S. Obika, M. Shinoda
Tetrahedron 185 134840
Phthalimide: a potential warhead for switchable and bioorthogonal conjugation
Kosuke Chiba, Takumi Yoshida, Kana Okada, Minory Ishikawa, Yuichi Hashimoto, Satoshi Obika, Takao Yamaguchi
Chem. Commun. 61 13417–13420
Unraveling and controlling late-onset neurotoxicity of antisense oligonucleotides through strategic chemical modifications
Takayuki Kuroda, Kotaro Yoshioka, Su Su Lei Mon, Maho Katsuyama, Kumiko Sato, Eriko Isogai, Kie Yoshida-Tanaka, Rintaro Iwata-Hara, Takao Yamaguchi, Satoshi Obika, Takanori Yokota
Mol. Ther. Nucleic Acids 36 102692
Development of a Synthetic Lethality-Based Combination Therapy Using LIG1 and PARP Inhibitors for Prostate Cancer
Masaru Tani, Koji Hatano, Yu Ishizuya, Toshiki Oka, Tomohiro Kanaki, Shunsuke Inoguchi, Akihiro Yoshimura, Yuki Horibe, Yutong Liu, Sassi Nesrine, Yohei Okuda, Akinaru Yamamoto, Toshihiro Uemura, Gaku Yamamichi, Takuji Hayashi, Yoshiyuki Yamamoto, Taigo Kato, Atsunari Kawashima, Takao Yamaguchi, Satoshi Obika, Kosuke Yusa, Norio Nonomura, Keisuke Nimura
Cancer Science 116 3403–3416
Rational design of a covalent ACE2 decoy receptor that broadly neutralizes SARS-CoV-2 variants
Nobumasa Hino, Risa Takada, Kyosuke Suzuki, Nagisa Tokunoh, Tatsuya Karaki, Kazumasa Ohtake, Haruna Ogami, Takafumi Nishiura, Kenji Ishimoto, Tomohito Tsukamoto, Yukio Ago, Yoshiaki Okada, Toru Okamoto, Chikako Ono, Yoshiharu Matsuura, Satoshi Obika, Kensaku Sakamoto, Yasuo Yoshioka, Shinsaku Nakagawa
Protein Science 34 e70306
Cycloalkane incorporation into the 2′,4′-bridge of locked nucleic acid: enhancing nuclease stability, reducing phosphorothioate modifications, and lowering hepatotoxicity in antisense oligonucleotides
Takao Yamaguchi, Hibiki Komine, Takaya Sugiura, Riku Kumagai, Tokuyuki Yoshida, Kiyomi Sasaki, Taisuke Nakayama, Haruhiko Kamada, Takao Inoue, Satoshi Obika
JACS Au 5 5111–5120
Hydrophilic additives enhancing electrospray ionization of oligonucleotides in hexafluoro-2-propanol-free reversed-phase ion-pair liquid chromatography/mass spectrometry
Takashi Miyazaki, Natsuyo Asano, Satoshi Yamaki, Takao Yamaguchi, Satoshi Obika
J. Chromatogr. A 1765 466485
Development of synthetic routes to 2′-O,4′-C-spirocyclopentylene-bridged nucleic acids: thymidine, guanosine, and adenosine
Riku Kumagai, Riko Yamada, Takao Yamaguchi, Satoshi Obika
Chem. Eur. J. 31 e02995
Sequence-dependent RNA cleavage by the 8–17 DNAzyme: Identification of preferred tetranucleotide motifs
Satoko Nakajima, Shuhei Miyakawa, Shu Ohno, Haruki Ikemoto, Rikuto Maruyama, Kosuke Chiba, Ryota Suginakaa, Chihiro Oda, Yuuya Kasahara, Kaori Fukuzawa, Satoshi Obika, Takao Yamaguchi
Bioorg. Med. Chem. 134 118520
Regulation of Duplex Formation in Response to pH and Comple-mentary RNA: Development of Oligonucleotides Modified with S-Methylthioimidate-Bridged Nucleic Acid and Evaluation of Their Function
T. Osawa, K. Miyata, S. Ito, K. Uda, S. Obika
ACS Omega
■総説
Developing Methods for the Synthesis of Ligand–Oligonucleotide Conjugates for Drug Discovery Applications
T. Osawa
Chem. Pharm. Bull. 73 762–771
Current Trends in Liquid Chromatography-Mass Spectrometry Analysis of Small Interfering RNAs: A Short Review
Hiroyuki Togawa, Takao Yamaguchi, Junji Kawakami, Satoshi Obika
J. Chromatogr. A 1766 466550
T. Osawa
Chem. Pharm. Bull. 73 762–771
Current Trends in Liquid Chromatography-Mass Spectrometry Analysis of Small Interfering RNAs: A Short Review
Hiroyuki Togawa, Takao Yamaguchi, Junji Kawakami, Satoshi Obika
J. Chromatogr. A 1766 466550
■著書
未来の核酸医薬に貢献できる技術開発を目指して
大澤昂志
生産と技術 77 57–59
大澤昂志
生産と技術 77 57–59
2024
■論文
Light-controllable cell-membrane disturbance for intracellular delivery
W. Huo, K. Miki, H. Mu, T. Osawa, H. Yamaguma, Y. Kasahara, S. Obika, Y. Kawaguchi, H. Hirose, S. Futaki, Y. Miyazaki, W. Shinoda, S. Akai, K. Ohe
J. Mater. Chem. B, 12(17), 4138–4147.
A novel transient receptor potential C3/C6 selective activator induces the cellular uptake of antisense oligonucleotides
H. Kohashi, R. Nagata, Y. Tamenori, T. Amatani, Y. Ueda, Y. Mori, Y. Kasahara, S. Obika, M. Shimojo
Nucleic Acids Res.
Separation of the diastereomers of phosphorothioated siRNAs by anion-exchange chromatography under non-denaturing conditions
H. Togawa, T. Okubo, K. Horiuchi, T. Yamaguchi, E. Tomita-Sudo, T. Akita, J. Kawakami, S. Obika
J. Chromatogr. A, 1721, 464847.
Favorable Efficacy and Reduced Acute Neurotoxicity by Antisense Oligonucleotides with 2',4'-BNA/LNA with 9-(aminoethoxy)phenoxazine
T. Matsubayashi, K. Yoshioka, S. S. L. Mon, M. Katsuyama, C. Jia, T. Yamaguchi, R. Iwata-Hara, T. Nagata, O. Nakagawa, S. Obika, T. Yokota
Mol. Ther. Nucleic Acids
Synthesis of coumarin-conjugated oligonucleotides via Knoevenagel condensation to prepare an oligonucleotide library
T. Osawa, S. Obika
Chem. Pharm. Bull., 72(2), 143–148.
Synthesis, duplex-forming ability, and enzymatic stability of oligonucleotides modified with amide-linked dinucleotides containing a 3′,4′-tetrahydropyran-bridged nucleic acid
T. Osawa, T. Akino, S. Obika
J. Org. Chem. 89(1), 269–280.
Development of a simple purification method for oligonucleotides synthesized by using a phosphoramidite for 5'-end modification as a capping reagent
Q. Ren, T. Osawa, S. Obika
Tetrahedron, 150, 133774.
Introduction of sugar-modified nucleotides into CpG-containing antisense oligonucleotides inhibits TLR9 activation
Tokuyuki Yoshida, Tomoko Hagihara, Yasunori Uchida, Yoshiyuki Horiuchi, Kiyomi Sasaki, Takenori Yamamoto, Takuma Yamashita, Yukihiro Goda, Yoshiro Saito, Takao Yamaguchi, Satoshi Obika, Seiji Yamamoto and Takao Inoue
Sci. Rep. 14 11540
In vitro screening of chemically synthesized dipeptide-antisense oligonucleotide conjugates to identify ligand molecules enhancing their activity
T. Osawa, R. Kita, Y. Kasahara, H. Yamaguma, T. Nakayama, H. Kamada, S. Obika
Bioorg. Med. Chem. 110 117814
THF peroxide as a factor in generating desulphurised products from the solid-phase synthesis of phosphorothioate-modified oligonucleotides
Q. Ren, T. Osawa, M. Tatsuno, S. Obika
RSC Adv. 14(30) 21590–21596
Separation and characterization of therapeutic oligonucleotide isomer impurities by cyclic ion mobility-mass spectrometry
S. Omuro, T. Yamaguchi, T. Kawase, K. Hirose, T. Yoshida, T. Inoue, S. Obika
J. Am. Soc. Mass Spectrom. 35 2156-2164
DNAコード化ライブラリーへの応用を志向したクマリン−オリゴ核酸コンジュゲートの合成
大澤昂志
薬学雑誌 144(10) 931–936
Dual-modified Antisense Oligonucleotides Targeting Oncogenic Protocadherin to Treat Gastric Cancer
M. Kanda, Y. Kasahara, D. Shimizu, T. Shinozuka, M. Sasahara, S. Nakamura, Y. Iguchi, M. Katsuno, Y. Kodera, S. Obika
Br. J. Cancer 131 1555-1566
Preclinical Toxicological Assessment of Amido-bridged Nucleic Acid-modified Antisense Oligonucleotides Targeting Synaptotagmin XIII for Intra-abdominal Treatment of Peritoneal Metastasis of Gastric Cancer
M. Kanda, N. Takano, H. Miyauchi, K. Ueda, M. Mizuno, Y. Kasahara, Y. Kodera, S. Obika
Gastric Cancer 27 1229-1241
Splice-switching Antisense Oligonucleotide Controlling Tumour Suppressor REST Is a Novel Therapeutic Medicine for Neuroendocrine Cancer
K. Mishima, S. Obika, M. Shimojo
Mol. Ther. Nucleic Acids 35 102250
Polyamines Promote Xenobiotic Nucleic Acid Synthesis by Modified Thermophilic Polymerase Mutants
H. Hoshino, Y. Kasahara, S. Obika
RSC Chem. Biol 5 467-472
W. Huo, K. Miki, H. Mu, T. Osawa, H. Yamaguma, Y. Kasahara, S. Obika, Y. Kawaguchi, H. Hirose, S. Futaki, Y. Miyazaki, W. Shinoda, S. Akai, K. Ohe
J. Mater. Chem. B, 12(17), 4138–4147.
A novel transient receptor potential C3/C6 selective activator induces the cellular uptake of antisense oligonucleotides
H. Kohashi, R. Nagata, Y. Tamenori, T. Amatani, Y. Ueda, Y. Mori, Y. Kasahara, S. Obika, M. Shimojo
Nucleic Acids Res.
Separation of the diastereomers of phosphorothioated siRNAs by anion-exchange chromatography under non-denaturing conditions
H. Togawa, T. Okubo, K. Horiuchi, T. Yamaguchi, E. Tomita-Sudo, T. Akita, J. Kawakami, S. Obika
J. Chromatogr. A, 1721, 464847.
Favorable Efficacy and Reduced Acute Neurotoxicity by Antisense Oligonucleotides with 2',4'-BNA/LNA with 9-(aminoethoxy)phenoxazine
T. Matsubayashi, K. Yoshioka, S. S. L. Mon, M. Katsuyama, C. Jia, T. Yamaguchi, R. Iwata-Hara, T. Nagata, O. Nakagawa, S. Obika, T. Yokota
Mol. Ther. Nucleic Acids
Synthesis of coumarin-conjugated oligonucleotides via Knoevenagel condensation to prepare an oligonucleotide library
T. Osawa, S. Obika
Chem. Pharm. Bull., 72(2), 143–148.
Synthesis, duplex-forming ability, and enzymatic stability of oligonucleotides modified with amide-linked dinucleotides containing a 3′,4′-tetrahydropyran-bridged nucleic acid
T. Osawa, T. Akino, S. Obika
J. Org. Chem. 89(1), 269–280.
Development of a simple purification method for oligonucleotides synthesized by using a phosphoramidite for 5'-end modification as a capping reagent
Q. Ren, T. Osawa, S. Obika
Tetrahedron, 150, 133774.
Introduction of sugar-modified nucleotides into CpG-containing antisense oligonucleotides inhibits TLR9 activation
Tokuyuki Yoshida, Tomoko Hagihara, Yasunori Uchida, Yoshiyuki Horiuchi, Kiyomi Sasaki, Takenori Yamamoto, Takuma Yamashita, Yukihiro Goda, Yoshiro Saito, Takao Yamaguchi, Satoshi Obika, Seiji Yamamoto and Takao Inoue
Sci. Rep. 14 11540
In vitro screening of chemically synthesized dipeptide-antisense oligonucleotide conjugates to identify ligand molecules enhancing their activity
T. Osawa, R. Kita, Y. Kasahara, H. Yamaguma, T. Nakayama, H. Kamada, S. Obika
Bioorg. Med. Chem. 110 117814
THF peroxide as a factor in generating desulphurised products from the solid-phase synthesis of phosphorothioate-modified oligonucleotides
Q. Ren, T. Osawa, M. Tatsuno, S. Obika
RSC Adv. 14(30) 21590–21596
Separation and characterization of therapeutic oligonucleotide isomer impurities by cyclic ion mobility-mass spectrometry
S. Omuro, T. Yamaguchi, T. Kawase, K. Hirose, T. Yoshida, T. Inoue, S. Obika
J. Am. Soc. Mass Spectrom. 35 2156-2164
DNAコード化ライブラリーへの応用を志向したクマリン−オリゴ核酸コンジュゲートの合成
大澤昂志
薬学雑誌 144(10) 931–936
Dual-modified Antisense Oligonucleotides Targeting Oncogenic Protocadherin to Treat Gastric Cancer
M. Kanda, Y. Kasahara, D. Shimizu, T. Shinozuka, M. Sasahara, S. Nakamura, Y. Iguchi, M. Katsuno, Y. Kodera, S. Obika
Br. J. Cancer 131 1555-1566
Preclinical Toxicological Assessment of Amido-bridged Nucleic Acid-modified Antisense Oligonucleotides Targeting Synaptotagmin XIII for Intra-abdominal Treatment of Peritoneal Metastasis of Gastric Cancer
M. Kanda, N. Takano, H. Miyauchi, K. Ueda, M. Mizuno, Y. Kasahara, Y. Kodera, S. Obika
Gastric Cancer 27 1229-1241
Splice-switching Antisense Oligonucleotide Controlling Tumour Suppressor REST Is a Novel Therapeutic Medicine for Neuroendocrine Cancer
K. Mishima, S. Obika, M. Shimojo
Mol. Ther. Nucleic Acids 35 102250
Polyamines Promote Xenobiotic Nucleic Acid Synthesis by Modified Thermophilic Polymerase Mutants
H. Hoshino, Y. Kasahara, S. Obika
RSC Chem. Biol 5 467-472
■著書
アンチセンス核酸およびsiRNA技術
大澤昂志、小比賀聡
The Lipid, 35(1), 14–19.
アンチセンス核酸
山口卓男
核酸医薬〜モダリティ・合成・分析・DDSの最新動向〜, 17–25.
修飾核酸の合成
大澤昂志
核酸医薬〜モダリティ・合成・分析・DDSの最新動向〜, 67–74.
安全で有効なアンチセンス核酸医薬の開発に向けて
山口卓男、小比賀聡
未来社会共創を目指す 研究シーズ集2024, 54.
Chapter 9: Oligonucleotide Synthesis and State-of-the-Art Drug Discovery
T. Osawa, S. Obika
Sustainability in Tides Chemistry: Green Approaches to Oligonucleotides and Oligopeptides Synthesis 194–227
大澤昂志、小比賀聡
The Lipid, 35(1), 14–19.
アンチセンス核酸
山口卓男
核酸医薬〜モダリティ・合成・分析・DDSの最新動向〜, 17–25.
修飾核酸の合成
大澤昂志
核酸医薬〜モダリティ・合成・分析・DDSの最新動向〜, 67–74.
安全で有効なアンチセンス核酸医薬の開発に向けて
山口卓男、小比賀聡
未来社会共創を目指す 研究シーズ集2024, 54.
Chapter 9: Oligonucleotide Synthesis and State-of-the-Art Drug Discovery
T. Osawa, S. Obika
Sustainability in Tides Chemistry: Green Approaches to Oligonucleotides and Oligopeptides Synthesis 194–227
大阪大学大学院 薬学研究科 生物有機化学分野
〒565‐0871 大阪府吹田市山田丘1-6
TEL: 06-6879-8200 FAX: 06-6879-8204
obika@phs.osaka-u.ac.jp
〒565‐0871 大阪府吹田市山田丘1-6
TEL: 06-6879-8200 FAX: 06-6879-8204
obika@phs.osaka-u.ac.jp