ArticleMolecular diagnosis & therapy2021
Using RNA-seq to Assess Off-Target Effects of Antisense Oligonucleotides in Human Cell Lines.
Article in Molecular diagnosis & therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 23 citations in OpenAlex.
- Chemical Modification Strategies for Therapeutic Oligonucleotides: Mechanism Compatibility, Design Trade-Offs, and Translational Barriers.Molecules (Basel, Switzerland) · 2026Review
- RNA Therapeutics Targeting Skeletal Muscle: Emerging Antisense and Gene-Modifying Strategies.Biomolecules · 2026Review
- Enhancing diabetes treatment by targeted nucleic acid and drug delivery using cell-penetrating peptides, peptide nucleic acids, and receptor targeting.Frontiers in pharmacology · 2026Review
- Genetic therapies for neurological diseases.Pharmacological reviews · 2026Review
- Determining off-target effects of splice-switching antisense oligonucleotides using short read RNAseq in neuronally differentiated human induced pluripotent stem cells.Human molecular genetics · 2025Article
- Article
- Non-coding RNAs in heart failure: epigenetic regulatory mechanisms and therapeutic potential.Frontiers in genetics · 2025Review
- RNA Sequencing in Disease Diagnosis.Annual review of genomics and human genetics · 2024Review
- Considerations in the Preclinical Assessment of the Safety of Antisense Oligonucleotides.Nucleic acid therapeutics · 2023Review
- Article
- PAM-altering SNP-based allele-specific CRISPR-Cas9 therapeutic strategies for Huntington's disease.Molecular therapy. Methods & clinical development · 2022Article
- Specificity of oligonucleotide gene therapy (OGT) agents.Theranostics · 2022Review
- Reduction of Off-Target Effects of Gapmer Antisense Oligonucleotides by Oligonucleotide Extension.Molecular diagnosis & therapy · 2022Article
- Transcriptome-Wide Off-Target Effects of Steric-Blocking Oligonucleotides.Nucleic acid therapeutics · 2021Article
- Slivers of the spectrum.Nature biotechnology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe field of antisense oligonucleotide therapeutics is rapidly growing and in addition to small molecules and therapeutic antibodies, oligonucleotide-based gene expression modifiers have been developed as fully accepted therapeutics. Antisense oligonucleotides are designed to modify gene expression of their specific target genes. However, as their effect relies on Watson-Crick base pairing, they could also bind to other unintended complementary RNAs showing sufficient sequence homology, which in turn could lead to off-target effects. It is assumed that these off-target effects depend on the degree of complementarity between the antisense oligonucleotides and off-target sequences.
objectiveAim of this study was the investigation of the effects of antisense oligonucleotides on the expression of potential off-targets having a defined number of mismatches to the oligonucleotide sequence.
methodsWe extend recent studies by investigating the off-target profile of two 17-mer antisense oligonucleotides in two distinct human cell lines by a whole-transcriptome study using RNA sequencing.
resultsThe relatively high percentage of significantly downregulated off-target genes for which one mismatch is present corroborates the requirement for intense bioinformatic screens and stringent specificity criteria to design antisense oligonucleotides with only minimal sequence complementarity to any non-target sequence.
conclusionsAvoiding suppression of off-target genes by a thorough bioinformatics screen should strongly reduce the risk for toxicities caused by antisense oligonucleotide-mediated off-target RNA suppression and finally result in safer antisense oligonucleotide-based therapeutics.
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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.