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2026
■Article
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.

■Reviews
■Book
2025
■Articles
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

ATP binding controls the molecular function of bacterial MutS2 by mediating closure of the dimeric clamp structure.
Kenji Fukui, Takeshi Murakawa, Nobumasa Hino, Naoyuki Kondo, Takato Yano
Structure 33 1007-1015.e4

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

Claudin 5-binding small molecule transiently opens the blood-brain barrier and safely enhances brain drug delivery
Saito Inoue, Keisuke Shirakura, Atsuya Shirono, Jumpei Taguchi, Yoshiki Ikeda, Satomi Tomita, Risa Funatsu, Kosuke Muraoka, Yosuke Hashimoto, Keisuke Tachibana, Nobumasa Hino, Takefumi Doi, Yui Ikemi, Kazuto Nunomura, Bangzhong Lin, Shinsaku Nakagawa, Kazutake Tsujikawa, Shota Tanaka, Masanori Obana, Yasushi Fujio, Takamitsu Hosoya, Hiroyuki Takeda, Masuo Kondoh, Yoshiaki Okada
Journal of controlled release 388 114314

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

The effect of silicon-based agent on allergic bronchitis caused by ragweed pollen
H. Takeuchi, S. Takashima, M. Taya, N. Hino, C. Kakinuma, Y. Kobayashi, H. Kobayashi, S. Nakagawa
European Review for Medical and Pharmacological Sciences 29 578-586

Genetic Encoding of a Trifunctional Photo-Cross-Linker with a Cleavable Alkyl Ester Moiety
Masahiro Takayama, Tomoya Tsubota, Takao Yamaguchi, Kosuke Chiba, Takumi Yoshida, Yoshiyuki Hari, Yu-Shi Tian, Daisuke Takaya, Asuka Mori, Tomohito Tsukamoto, Kenji Ishimoto, Yukio Ago, Yoshiaki Okada, Kensaku Sakamoto, Takefumi Doi, Kaori Fukuzawa, Satoshi Obika, Shinsaku Nakagawa, Nobumasa Hino
ChemBioChem

Neuron-specific overexpression of human vasoactive intestinal peptide receptor 2 in mice causes cognitive dysfunction and abnormal dendritic morphology in the prefrontal cortex
Ami Ono, Tatsunori Miyaoka, Daichi Koan, Zihao Jin, Lu Chen, Atsuko Hayata-Takano, Satoshi Asano, Rei Yokoyama, Kenji Ishimoto, Nobumasa Hino, Akihiro Harada, Takanobu Nakazawa, Hitoshi Hashimoto, James A. Waschek, Shinsaku Nakagawa, Kotaro Tanimoto, Yukio Ago
Journal of Pharmacological Sciences 160 111-121

■Reviews
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

■Book
Aiming to Develop Technologies That Contribute to Future Oligonucleotide Therapeutics
Takashi Osawa
Manufacturing & Technology 77 57–59

2024
■Articles
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

Synthesis of coumarin-oligonucleotide conjugates for DNA-encoded library applications
Takashi Osawa
Biological and Pharmaceutical Bulletin 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

■Reviews
Antisense nucleic acid and siRNA technology
Takashi Osawa、Satoshi Obika
The Lipid, 35(1), 14–19.

Antisense nucleic acid
Takao Yamaguchi
Nucleic acid drugs - latest trends in modality, synthesis, analysis, and DDS 〜, 17–25.

Synthesis of modified nucleic acids
Takashi Osawa
Nucleic acid drugs - latest trends in modality, synthesis, analysis, and DDS 〜, 67–74.

Towards the development of safe and effective antisense nucleic acid medicines
Takao Yamaguchi, Satoshi Obika
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

■Book

Bioorganic Chemistry, Graduate School of Pharmaceutical Sciences, The University of Osaka
1-6 Yamadaoka, Suita, Osaka 565-0871, Japan
TEL:+81-6-6879-8200 FAX:+81-6-6879-8204
obika * phs.osaka-u.ac.jp (Change the * to @)