Evidence map›Paper›PMID 38042877›Full record

ArticleNature communications2023

Dynamic and static control of the off-target interactions of antisense oligonucleotides using toehold chemistry.

Chisato Terada, Kaho Oh, Ryutaro Tsubaki, Bun Chan, Nozomi Aibara, Kaname Ohyama, Masa-Aki Shibata, Takehiko Wada, Mariko Harada-Shiba, Asako Yamayoshi and 1 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
2.5field-weighted citation impact, top 11% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed, 16 citations in OpenAlex.

  1. Review
  2. Review
  3. Allele-specific antisense oligonucleotide treatment rescuesbioRxiv : the preprint server for biology · 2026
    Article
  4. Review
  5. Article
  6. Article
  7. Review
  8. Genetic therapies for neurological diseases.Pharmacological reviews · 2026
    Review
  9. Article
  10. Review
  11. Article
  12. Article
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  14. Article
  15. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 6 institutions in 1 country.

Chisato TeradaDepartment of Chemistry of Biofunctional Molecules, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Kaho OhDepartment of Chemistry of Biofunctional Molecules, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Ryutaro TsubakiDepartment of Chemistry of Biofunctional Molecules, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
Bun ChanGraduate School of Engineering, Nagasaki University, Nagasaki, Japan.ORCID 0000-0002-0082-5497
Nozomi AibaraDepartment of Pharmacy Practice, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.ORCID 0000-0001-8323-0036
Kaname OhyamaDepartment of Molecular Pathochemistry, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.ORCID 0000-0002-1449-5505
Masa-Aki ShibataDepartment of Anatomy and Cell Biology, Faculty of Medicine, Osaka Medical and Pharmaceutical University, Takatsuki, Japan.
Takehiko WadaInstitute of Multidisciplinary Research for Advanced Materials (IMRAM), Tohoku University, Sendai, Miyagi, Japan.
Mariko Harada-ShibaDepartment of Molecular Innovation in Lipidology, National Cerebral and Cardiovascular Center Research Institute, Suita, Japan.ORCID 0000-0002-7600-2059
Asako YamayoshiDepartment of Chemistry of Biofunctional Molecules, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.ORCID 0000-0002-7527-4255
Tsuyoshi YamamotoDepartment of Chemistry of Biofunctional Molecules, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan. tsuyoshi.yamamoto@nagasaki-u.ac.jp.ORCID 0000-0002-3206-2455
Nagasaki University · JPJapan Society for the Promotion of Science · JPNational Cerebral and Cardiovascular Center · JPOsaka University of Pharmaceutical Sciences · JPTohoku University · JPUniversity of Nagasaki · JP

Funding

MEXT | Japan Society for the Promotion of Science (JSPS) 20H05874MEXT | Japan Society for the Promotion of Science (JSPS) 22H02783MEXT | Japan Society for the Promotion of Science (JSPS) JP22J20853MEXT | Japan Society for the Promotion of Science (JSPS) JP22KJ2503
6 · The paper itself

Abstract

Off-target interactions between antisense oligonucleotides (ASOs) with state-of-the-art modifications and biological components still pose clinical safety liabilities. To mitigate a broad spectrum of 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 on-target 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.

Indexed as

Oligonucleotides, AntisensePeptide Nucleic AcidsHumansMaleNucleic Acid HybridizationPhosphorothioate OligonucleotidesProtein BindingRNAOligonucleotides, AntisensePeptide Nucleic AcidsPhosphorothioate OligonucleotidesRNA

Identifiers

PMID38042877
PMCPMC10693639
OpenAlexW4389267239

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.