ArticleMolecular therapy. Nucleic acids2018
A Sensitive In Vitro Approach to Assess the Hybridization-Dependent Toxic Potential of High Affinity Gapmer Oligonucleotides.
Article in Molecular therapy. Nucleic acids, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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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.
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Who cites it
42 citing papers in PubMed, 70 citations in OpenAlex.
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- Single-base 2'OMe-modified LNA and MOE gapmers selectively silenceMolecular therapy. Nucleic acids · 2026Article
- Integrating transcriptomics and proteomics to assess antisense oligonucleotide safety and efficacy: a time-resolved approach.NAR molecular medicine · 2026Article
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- LncRNA Knockdown Using Gapmer Antisense Oligonucleotides.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Development and Clinical Applications of Antisense Oligonucleotide Gapmers.Methods in molecular biology (Clifton, N.J.) · 2026Article
- A novel bispecific siRNA concept: Efficient dual knockdown ofMolecular therapy. Nucleic acids · 2025Article
- Angelman syndrome patient-derived neuron screen leads to clinical ASO rugonersen targeting UBE3A-ATS with long-lasting effect in monkeys.Nucleic acids research · 2025Article
- Chemical Modifications in Nucleic Acid Therapeutics.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Application of 4'-RSC advances · 2024Article
- Dual-modified antisense oligonucleotides targeting oncogenic protocadherin to treat gastric cancer.British journal of cancer · 2024Article
- Construction of aMolecular therapy. Nucleic acids · 2024Article
- Promising strategies employing nucleic acids as antimicrobial drugs.Molecular therapy. Nucleic acids · 2024Review
- Antisense oligonucleotides and their applications in rare neurological diseases.Frontiers in neuroscience · 2024Review
- Dynamic and static control of the off-target interactions of antisense oligonucleotides using toehold chemistry.Nature communications · 2023Article
- Current Status of Oligonucleotide-Based Protein Degraders.Pharmaceutics · 2023Review
- Considerations in the Preclinical Assessment of the Safety of Antisense Oligonucleotides.Nucleic acid therapeutics · 2023Review
- Chemistry of Therapeutic Oligonucleotides That Drives Interactions with Biomolecules.Pharmaceutics · 2022Review
- Knockdown of the long noncoding RNA PURPL induces apoptosis and sensitizes liver cancer cells to doxorubicin.Scientific reports · 2022Article
- Identification of nucleobase chemical modifications that reduce the hepatotoxicity of gapmer antisense oligonucleotides.Nucleic acids research · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The successful development of high-affinity gapmer antisense oligonucleotide (ASO) therapeutics containing locked nucleic acid (LNA) or constrained ethyl (cEt) substitutions has been hampered by the risk of hepatotoxicity. Here, we present an in vitro approach using transfected mouse fibroblasts to predict the potential hepatic liabilities of LNA-modified ASOs (LNA-ASOs), validated by assessing 236 different LNA-ASOs with known hepatotoxic potential. This in vitro assay accurately reflects in vivo findings and relates hepatotoxicity to RNase H1 activity, off-target RNA downregulation, and LNA-ASO-binding affinity. We further demonstrate that the hybridization-dependent toxic potential of LNA-ASOs is also evident in different cell types from different species, which indicates probable translatability of the in vitro results to humans. Additionally, we show that the melting temperature (T
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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.