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).


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. Bridged nucleic acids

There are four different bridged nucleic acids.

Modification of XNAs:Best material group for antisense applications



  • Improvement of nuclease resistance
  • Improvement of base-specific hybrid
  • Reduction in hepatotoxicity
  • Establishment of a basic production method for monomers


  • Improvement of nuclease resistance
  • Improvement of base-specific hybrid
  • Improvement of cell internalization (by positive charge in the structure)


  • Improvement of nuclease resistance
  • Improvement of base-specific hybrid
  • Reduction in hepatotoxicity
  • Add hydrophobicity in the sequence


  • Improvement of nuclease resistance
  • Improvement of base-specific hybrid
  • Reduction of hepatotoxicity and neurotoxicity

Hepatotoxicity risks significantly decreased
compared to the earlier LNA technology.
Various oligonucleotide therapeutics with

different characteristics.

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 ++++ ++ +++++
S-cEt Bi-cyclic ++++ +++ + +++++++
AmNA™ Bi-cyclic ++++ +++ + +++
GuNA™ Bi-cyclic ++++ ++++ + ++++
scpBNA™ Bi-cyclic ++++ +++++ + ++++
5′-CP™ non-bridge ++ ++++ +

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.


  • AmNA®

    Yahara A1, 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 Nov 26;13(17):2513-6

    Yamamoto T1, 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 Mar 28;13(12):3757-65

    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).

  • GuNA®

    Shrestha AR1, 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 (Camb). 2014 Jan 18;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 Sep 11;16(35):6531-6536.

  • scpBNA®

    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 Nov 18;81(22):11000-11008.

    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 (Camb). 2015 Jun 14;51(47):9737-40.

  • Reduction of Hepatotoxicity through Base Modification

    Yoshida, T. Morihiro, K. Naito, Y. Mikami, A. Kasahara, Y. Inoue, T. Obika, S.
    Identification of Nucleobase Chemical Modifications That Reduce the Hepatotoxicity of Gapmer Antisense Oligonucleotides. Nucleic Acids Res 2022, 50 (13), 7224-7234.

  • Dual Modification (Base Modification of scpBNA)

    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 (1), 154-162

    Habuchi, T. Yamaguchi, T. Aoyama, H. Horiba, M. Ito, K. Obika, S.
    Hybridization and Mismatch Discrimination Abilities of 2′,4′-Bridged Nucleic Acids Bearing 2-Thiothymine or 2-Selenothymine Nucleobase. The Journal of Organic Chemistry 2019, 84, 3, 1430-1439