A collaborative research group led by Kumamoto University, Hirosaki University, Nagoya University, Kobe Pharmaceutical University, and StapleBio Inc. has developed a novel drug discovery approach termed RNA hacking (RNAh). This approach utilizes Staple oligomers—synthetic oligonucleotides that precisely recognize and hybridize with specific target mRNA—to artfully induce a highly stable RNA G-quadruplex (rG4) structure, thereby selectively suppressing protein expression.
Unlike conventional siRNA or antisense oligonucleotide (ASO), Staple oligomers exerts its pharmacological effects without relying on endogenous enzymatic reactions, allowing for flexible application of chemically modified nucleic acids. This feature enables the technology to overcome key limitations of traditional nucleic acid therapeutics, such as off-target effects and in vivo instability, making it a promising new platform for next-generation RNA therapy.
The study was published online in Nature Biomedical Engineering on October 15, 2025.
Article title :
Staple oligomers induce a stable RNA G-quadruplex structure for protein translation inhibition in therapeutics
Authors :
Yousuke Katsuda, Takuto Kamura, Tomoki Kida, Rinka Ohno, Shuhei Shiroto, Yua Hasegawa, Kaito Utsumi, Yuki Sakamoto, Shinichiro Nakamura, Taishi Nakamura, Kenichi Tsujita, Yusuke Kitamura, Yukiko Kamiya, Hiroyuki Asanuma, Toshihiro Ihara, Masaki Hagihara, Shin-Ichi Sato
Nature Biomedical Engineering, 15 October (2025), doi: 10.1038/s41551-025-01515-4
https://www.nature.com/articles/s41551-025-01515-4