Platform of oligonucleotide therapeutics discovery

Our drug discovery platform consists of following basic technologies accumulated in Professor Obika’s laboratory (Osaka University Graduate School of Pharmaceutical Sciences, Bioorganic Chemistry).

配列設計技術

Advantages of Our Technology:

  • High binding affinity to the target mRNA.
  • Enhanced safety due to reduced liver toxicity and neurotoxicity.
  • Potential to target previously inaccessible locations within the body.
  • Ability to design specific antisense sequences.

1. Modified nucleic acids

We offer four modified nucleic acids, comprising three bridged nucleic acid analogs and one structurally enhancedDNA analog

Modified XNAs: Superior Platforms for Antisense Applications

AmNA™

AmNA™

  • Improvement of nuclease resistance
  • Improvement of base-specific hybridization
  • Reduction in hepatotoxicity
scpBNA™

scpBNA™

  • Improvement of nuclease resistance
  • Improvement of base-specific hybridization
  • Reduction in hepatotoxicity
  • Adds hydrophobicity in the sequence
GuNA™

GuNA™

  • Improvement of nuclease resistance
  • Improvement of base-specific hybridization
  • Apply a positive charge to the chain
  • Reduction in immunotoxicity
5'-CP™

5′-CP™

  • Improvement of nuclease resistance without phosphorothioation
  • Reduction in off-target effects
  • Reduction in hepato- and neurotoxicity

Hepatotoxicity risks significantly decreased
compared to the earlier LNA technology.
+
Diverse modified nucleic acids with
distinct characteristics for
oligonucleotide therapeutics.

Comparison with other modifications: Our modification group endows your oligonucleotides with superior properties.

Modification Type Hybridize Nuclease resistance Hepatotoxicity Mfg. Cost
PS DNA   + +++++ ++ +
2′-OMe 2′-modify ++ + ++
2′-F 2′-modify ++ + ++ ++
2′-MOE 2′-modify ++ ++ + +++
LNA Bi-cyclic ++++ ++ +++++
(Hepatotoxicity)
++++
S-cEt Bi-cyclic ++++ +++ + +++++++
AmNA™ Bi-cyclic ++++ +++ + +++
GuNA™ Bi-cyclic ++++ ++++ + ++++
scpBNA™ Bi-cyclic ++++ +++++ + ++++
5′-CP™ non-bridge ++ ++++ +
(neurotoxicity+)
++

Our modification

2. Antisense toxicity reduction technology

Antisense drugs are associated with the risk of hepatotoxicity.
At Osaka University, they discovered that the following technologies reduce hepatotoxicity by utilizing a new bridged nucleic acid and/or base modification incorporated into the oligonucleotide, and furthermore, they are developing technologies aiming at minimizing hepatotoxicity.

  • 1)Base modification of gap segment in gapmer antisense oligonucleotide
  • 2)Dual modification of wing segment in gapmer antisense oligonucleotide

This research was selected for AMED’s Cyclic Innovation for Clinical Empowerment (CiCLE) program.
Our company has obtained a comprehensive license from Osaka University for the patents generated through this research.

3. Sequence design system

It is important in the design process to decide in which mRNA area to develop antisense therapy.
Based on basic technologies accumulated in Osaka University and NIBIOHN, we are advancing our own research and setting up design technologies to obtain as many candidate sequences as we can.

Literature

  • AmNA

    Yahara A, Shrestha AR, Yamamoto T, Hari Y, Osawa T, Yamaguchi M, Nishida M, Kodama T, Obika S.
    Amido-Bridged Nucleic Acids (AmNAs): Synthesis, Duplex Stability, Nuclease Resistance, and in Vitro Antisense Potency, ChemBioChem, 2012, 13, 2513 – 2516

    Yamamoto T, Yahara A, Waki R, Yasuhara H, Wada F, Harada-Shiba M, Obika S.
    Amido-bridged nucleic acids with small hydrophobic residues enhance hepatic tropism of antisense oligonucleotides in vivo, Org Biomol Chem. 2015,13,12, 3757-65

    Setoguchi K, Cui L, Hachisuka N, Obchoei S, Shinkai K, Hyodo F, Kato K, Wada F, Yamamoto T, Harada-Shiba M, Obika S, Nakano K.
    Antisense Oligonucleotides Targeting Y-Box Binding Protein-1 Inhibit Tumor Angiogenesis by Downregulating Bcl-xL-VEGFR2/-Tie Axes, Molecular Therapy: Nucleic Acids, 2017, 9, 170-181

    Shimojo M, Kasahara Y, Inoue M, Tsunoda S, Shudo Y, Kurata T, Obika S.
    A Gapmer Antisense Oligonucleotide Targeting SRRM4 Is a Novel Therapeutic Medicine for Lung. Cancer, Sci. Rep. 2019, 9,1

    Uehara T, Choong CJ, Nakamori M, Hayakawa H, Nishiyama K, Kasahara Y, Baba K, Nagata T, Yokota T, Tsuda H, Obika S, Mochizuki H.
    Amido-bridged Nucleic Acid (AmNA)-modified Antisense Oligonucleotides Targeting -synuclein As A Novel Therapy For Parkinson’s disease, Scientific Reports, 2019, 9:7567

    Kanda M, Kasahara Y, Shimizu D, Miwa T, Umeda S, Sawaki K, Nakamura S, Kodera Y, Obika S.
    Amido-Bridged Nucleic Acid-Modified Antisense Oligonucleotides Targeting SYT13 to Treat Peritoneal Metastasis of Gastric Cancer, Molecular Therapy: Nucleic Acids, 2020, 22, 791-802

    Wada F, Yamamoto T, Kobayashi T, Tachibana K, Ito KR, Hamasaki M, Kayaba Y, Terada C, Yamayoshi A, Obika S, Harada-Shiba M.
    Drug Discovery and Development Scheme For Liver-targeting Bridged Nucleic Acid Antisense Oligonucleotides, Molecular Therapy: Nucleic Acids, 2021, 26, 957~969

    Shimo T, Nakatsuji Y, Tachibana K, Obika S.
    Design and In Vitro Evaluation of Splice-Switching Oligonucleotides Bearing Locked Nucleic Acids, Amido-Bridged Nucleic Acids, and Guanidine-Bridged Nucleic Acids, Int. J. Mol. Sci. 2021, 22, 3526.

    Yoshida M, Oda C, Mishima K, Tsuji I, Obika S, Shimojo M.
    An Antisense Amido-bridged Nucleic Acid Gapmer Oligonucleotide Targeting SRRM4 Alters REST Splicing And Exhibits Anti-tumor Effects in Small Cell Lung Cancer And Prostate Cancer Cells, Cancer Cell Int, 2023, 23, 8

    Kanda M, Takano N, Miyauchi H, Ueda K, Mizuno M, Kasahara Y, Kodera Y, Obika S.
    Preclinical Toxicological Assessment of Amido‑bridged Nucleic Acid‑modified Antisense Oligonucleotides Targeting Synaptotagmin XIII For Intra‑abdominal Treatment Of Peritoneal Metastasis Of Gastric Cancer, Gastric Cancer , 2024, 27,1229–1241

    Kuroda M, Kasahara Y, Hirose M, Yamaguma H, Oda M, Nagao C, Mizuguchi K.
    Construction of a Tm-value prediction model and molecular dynamics study of AmNA-containing gapmer antisense oligonucleotide, Molecular Therapy: Nucleic Acids, 2024, 35, 3, 102272

    Uchibori Y, Suekuni M, Kokaji Y, Yoshida K, Kiyono T, Kasahara Y, Fujita M.
    AmNA-Modified Antisense Oligonucleotide Targeting MCM8 as a Cancer-Specific Chemosensitizer for Platinum Compounds, Cancer Science, 2025; 116, 1405–1416

    Kawanobe T, Asano S, Kandori H, Aoki M, Shrestha AR, Sekiguchi K, Yokoyama K, Fukuda R, Umemoto T.
    Hepatotoxicity Reduction Profiles of Antisense Oligonucleotides Containing Amido-Bridged Nucleic Acid and 2′-O,4′-C-Spirocyclopropylene Bridged Nucleic Acid, Nucleic Acid Ther, 2025, 35, 3, 114-124

    Sowa N, Horie T, Ide Y, Baba O, Kora K, Yoshida T, Nakamura Y, Matsumoto S, Matsushita K, Imanaka M, Zou F, Kume E, Kojima H, Qian Q, Kimura K, Otsuka R, Hara N, Yamasaki T, Otani C, Tsujisawa Y, Takaya T, Nishimura C, Watanabe D, Hasegawa K, Kotera J, Oka K, Fujita R, Takemiya A, Sasaki T, Kasahara Y, Obika S, Kimura T, Ono K.
    MicroRNA-33 inhibition ameliorates muscular dystrophy by enhancing skeletal muscle regeneration, EMBO Molecular Medicine, 2025, 17, 1902-1925

  • scpBNA

    https://www.glenresearch.com/reports/gr36-21

    Yamaguchi T, Horiba M, Obika S.
    Synthesis and Properties of 2’-O,4’-C-spirocyclopropylene Bridged Nucleic Acid (scpBNA), an Analogue of 2’,4’- BNA/LNA Bearing a Cyclopropane Ring, Chem. Commun., 2015, 51, 9737

    Horiba M, Yamaguchi T, Obika S.
    Synthesis of scpBNA-mC, -A, and -G Monomers and Evaluation of the Binding Affinities of scpBNA-Modified Oligonucleotides toward Complementary ssRNA and ssDNA, J. Org. Chem. 2016, 81, 22, 11000-11008.

    Kawanobe T, Asano S, Kandori H, Aoki M, Shrestha AR, Sekiguchi K, Yokoyama K, Fukuda R, Umemoto T.
    Hepatotoxicity Reduction Profiles of Antisense Oligonucleotides Containing Amido-Bridged Nucleic Acid and 2′-O,4′-C-Spirocyclopropylene Bridged Nucleic Acid, Nucleic Acid Ther, 2025, 35, 3, 114-124

  • Dual Modification (Base Modification of scpBNA)

    Habuchi T, Yamaguchi T, Aoyama H, Horiba M, Ito KR, Obika S.
    Hybridization and Mismatch Discrimination Abilities of 2′,4′-Bridged Nucleic Acids Bearing 2‑Thiothymine or 2‑Selenothymine Nucleobase, J. Org. Chem. 2019, 84, 1430-1439.

    Sakurai Y, Yamaguchi T, Yoshida T, Horiba M, Inoue T, Obika S.
    Synthesis and Properties of Nucleobase-Sugar Dual Modified Nucleic Acids: 2′‑OMe-RNA and scpBNA Bearing a 5‑Hydroxycytosine Nucleobase, J. Org. Chem., 2023, 88, 154−162

  • GuNA

    Shrestha AR, Kotobuki Y, Hari Y, Obika S.
    Guanidine Bridged Nucleic Acid (GuNA): an Effect of a Cationic Bridged Nucleic Acid on DNA Binding Affinity, Chem Commun 2014, 50, 5, 575-7

    Horie N, Kumagai S, Kotobuki Y, Yamaguchi T, Obika S.
    Facile Synthesis and Fundamental Properties of an N-methylguanidine-bridged Nucleic Acid (GuNA[NMe]), Org Biomol Chem. 2018,16, 35, 6531-6536.

    Kumagai S, Sawamoto H, Takegawa-Araki T, Arai Y, Yamakoshi S, Yamada K, Ohta Tetsuya, Kawanishi E, Horie N, Yamaguchi T, Obika S.
    Synthesis and Properties of GuNA purine/pyrimidine Nucleosides and Oligonucleotides, Org. Biomol. Chem., 2020, 18, 9461

    Horie N, Yamaguchi T, Kumagai S, Obika S.
    Synthesis and properties of oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing adenine, guanine, or 5-methylcytosine nucleobases, Beilstein J. Org. Chem. 2021, 17, 622–629.

    Shimo T, Nakatsuji Y, Tachibana K, Obika S.
    Design and In Vitro Evaluation of Splice-Switching Oligonucleotides Bearing Locked Nucleic Acids, Amido-Bridged Nucleic Acids, and Guanidine-Bridged Nucleic Acids, Int. J. Mol. Sci. 2021, 22, 3526.

    Takegawa-Araki T, Kumagai S. Yasukawa K, Kuroda M, Sasaki T, Obika S.
    Structure−Activity Relationships of Anti-microRNA Oligonucleotides Containing Cationic Guanidine-Modified Nucleic Acids, J. Med. Chem. 2022, 65, 2139−2148

    Sasaki T, Hirakawa Y, Yamairi F, Kurita T, Murahashi K, Nishimura H, Iwazaki N, Yasuhara H, Tateoka T, Ohta T, Obika S, Kotera Jun.
    Altered Biodistribution and Hepatic Safety Profile of a Gapmer Antisense Oligonucleotide Bearing Guanidine-Bridged Nucleic Acids, Nucleic Acid Ther, 2022, 32, 3, 177-184

    Yamaguchi T, Horie N, Aoyama H, Kumagai S, Obika S.
    Mechanism of the Extremely High Duplex-forming Ability of Oligonucleotides Modified With N-tert-butylguanidine- or N-tert-butyl-N′-methylguanidine-bridged Nucleic Acids Nucleic acid research, 2023, 51, 7749

  • 5′-CP

    Kuroda T, Yoshioka K, Mon SSL, Katsuyama M, Sato K, Isogai E, Yoshida-Tanaka K, Iwata-Hara R, Yamaguchi T, Obika S, Yokota T.
    Unraveling and controlling late-onset neurotoxicity of antisense oligonucleotides through strategic chemical modifications, Molecular Therapy: Nucleic Acids , 2025, September 12, 102692