@article{oai:nagasaki-u.repo.nii.ac.jp:02000434,
 author = {Terada, Chisato and Oh, Kaho and Tsubaki, Ryutaro and Chan, Bun and Aibara, Nozomi and Ohyama, Kaname and Shibata, Masa-Aki and Wada, Takehiko and Harada-Shiba, Mariko and Yamayoshi, Asako and Yamamoto, Tsuyoshi},
 issue = {1},
 journal = {Nature Communications},
 month = {Dec},
 note = {Off-target interactions between antisense oligonucleotides (ASOs) with stateof-the-art modifications and biological components still pose clinical safety liabilities. Tomitigate a broad spectrumof off-target interactions and enhance the safety profile of ASO drugs, we here devise a nanoarchitecture named BRace On a THERapeutic aSo (BROTHERS or BRO), which is composed of a standard gapmer ASO paired with a partially complementary peptide nucleic acid (PNA) strand. We show that these non-canonical ASO/PNA hybrids have reduced non-specific protein-binding capacity. The optimization of the structural and thermodynamic characteristics of this duplex system enables the operation of an in vivo toehold-mediated strand displacement (TMSD) reaction, effectively reducing hybridization with RNA off-targets. The optimized BROs dramatically mitigate hepatotoxicity while maintaining the ontarget knockdown activity of their parent ASOs in vivo. This technique not only introduces a BRO class of drugs that could have a transformative impact on the extrahepatic delivery of ASOs, but can also help uncover the toxicity mechanism of ASOs., Nature Communications, 14(1), art. no. 7972; 2023},
 title = {Dynamic and static control of the off-target interactions of antisense oligonucleotides using toehold chemistry},
 volume = {14},
 year = {2023}
}