ArticleNucleic acids research2022
Identification of nucleobase chemical modifications that reduce the hepatotoxicity of gapmer antisense oligonucleotides.
Article in Nucleic acids research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Small Nucleic Acid Therapeutics for Ocular Diseases: Progress, Challenges, and Future Perspectives.Pharmaceutics · 2026Review
- Chemical Modification Strategies for Therapeutic Oligonucleotides: Mechanism Compatibility, Design Trade-Offs, and Translational Barriers.Molecules (Basel, Switzerland) · 2026Review
- Review
- Acyclic artificial nucleic acid substitution expands the safe design space of gapmer ASOs by preventing P54nrb mislocalization.NAR molecular medicine · 2026Article
- Guanine base modifications in antisense oligonucleotides mitigate acute central nervous system toxicity.RSC chemical biology · 2026Article
- Direct targeting of C9ORF72 repeat RNA with fluorinated antisense oligonucleotides.Nucleic acids research · 2026Article
- Navigating the next frontier in biomedicine: breakthroughs and insights in nucleic acid therapeutics.Chemical science · 2026Review
- Designing nucleic acid-based therapeutics for cancer treatment: Updates on the state of the art.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Review
- Genetic therapies for neurological diseases.Pharmacological reviews · 2026Review
- Structural and Physicochemical Optimization of Next-Generation Antisense Oligonucleotide with BROTHERS for Mitigating Off-Target Effects.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Review
- Article
- Article
- Redesigning miR-34a: structural and chemical advances in the therapeutic development of an miRNA anti-cancer agent.Biochemical Society transactions · 2025Article
- ASOptimizer: optimizing chemical diversity of antisense oligonucleotides through deep learning.Nucleic acids research · 2025Article
- Amplified Production of a DNA Decoy Catalyzed by Intracellular MicroRNA.Angewandte Chemie (International ed. in English) · 2025Article
- Discovery and characterization of stereodefined PMO-gapmers targeting tau.Molecular therapy. Nucleic acids · 2025Article
- Advances and prospects of RNA delivery nanoplatforms for cancer therapy.Acta pharmaceutica Sinica. B · 2025Review
- Chemical Modifications in Nucleic Acid Therapeutics.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Evolution of antisense oligonucleotides: navigating nucleic acid chemistry and delivery challenges.Expert opinion on drug discovery · 2025Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Currently, gapmer antisense oligonucleotide (ASO) therapeutics are under clinical development for the treatment of various diseases, including previously intractable human disorders; however, they have the potential to induce hepatotoxicity. Although several groups have reported the reduced hepatotoxicity of gapmer ASOs following chemical modifications of sugar residues or internucleotide linkages, only few studies have described nucleobase modifications to reduce hepatotoxicity. In this study, we introduced single or multiple combinations of 17 nucleobase derivatives, including four novel derivatives, into hepatotoxic locked nucleic acid gapmer ASOs and examined their effects on hepatotoxicity. The results demonstrated successful identification of chemical modifications that strongly reduced the hepatotoxicity of gapmer ASOs. This approach expands the ability to design gapmer ASOs with optimal therapeutic profiles.
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Registered trials
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.