Acyclic artificial nucleic acid substitution expands the safe design space of gapmer ASOs by preventing P54nrb mislocalization.

Jumpei Ariyoshi, Masaya Higuchi, Hiroyuki Oyama, Hiroyuki Asanuma, Yukiko Kamiya

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Article in NAR molecular medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed

–field-weighted citation impact

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Jumpei AriyoshiLaboratory of Bioanalytical Chemistry, Kobe Pharmaceutical University, 4-19-1, Motoyamakita-machi, Higashinada-ku, Kobe 658-8558, Japan.ORCID https://orcid.org/0009-0004-8006-1897

Masaya HiguchiDepartment of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.

Hiroyuki OyamaLaboratory of Bioanalytical Chemistry, Kobe Pharmaceutical University, 4-19-1, Motoyamakita-machi, Higashinada-ku, Kobe 658-8558, Japan.ORCID https://orcid.org/0000-0002-5041-5701

Hiroyuki AsanumaDepartment of Biomolecular Engineering, Graduate School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.

Yukiko KamiyaLaboratory of Bioanalytical Chemistry, Kobe Pharmaceutical University, 4-19-1, Motoyamakita-machi, Higashinada-ku, Kobe 658-8558, Japan.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Gapmer-type antisense oligonucleotides (Gapmers) are promising therapeutic agents. However, their clinical potential is frequently limited by off-target toxicities. To address this issue, Gapmers have been optimized by modifying the ribose moiety or internucleotide linkage, but toxicity has not always been reduced. The toxicity is due to the unintended interactions between the ribose-type modified nucleic acids with phosphorothioate backbones and the endogenous proteins. We therefore hypothesized that the use of acyclic nucleic acids, which possess an entirely distinct structure to ribose, would solve the aforementioned issue. In this study, we demonstrate that the incorporation of an acyclic analog, serinol nucleic acid (SNA) or L-threoninol nucleic acid (L-

Identifiers

PMID42482706

DOI10.1093/narmme/ugag036

PMCPMC13385997

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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.