ArticleGenes2022
The siRNA Off-Target Effect Is Determined by Base-Pairing Stabilities of Two Different Regions with Opposite Effects.
Article in Genes, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed.
- From rules to foundation models: a comprehensive review of machine learning approaches for siRNA design.NAR genomics and bioinformatics · 2026Review
- Programmable protein degraders enable selective knockdown of pathogenic β-catenin subpopulations in vitro and in vivo.Science advances · 2026Article
- Article
- Strategic Computational Design of siRNA Molecules Targeting Structural Genes of SARS-CoV-2.Applied biochemistry and biotechnology · 2026Article
- Synthetic short RNA in cancer.Frontiers in oncology · 2026Review
- An siRMSD parameter of structural distortion induced by chemical modification is predictive of the off-target effect of siRNA.Molecular therapy. Nucleic acids · 2025Article
- Small Interfering RNA (siRNA) for Cardiorenal Disease: Mechanistic Insights from Preclinical and Clinical Studies.Journal of cardiovascular translational research · 2025Review
- Genomic medicine in hepatology: mechanisms and liver treatment strategies.Molecular medicine (Cambridge, Mass.) · 2025Review
- The concurrent silencing of Tim-3 and STAT-3 promotes tumor regression both in vitro and in ovo.BMC cancer · 2025Article
- Allele-specific depletion ofMolecular therapy. Oncology · 2025Article
- siRNA Features-Automated Machine Learning of 3D Molecular Fingerprints and Structures for Therapeutic Off-Target Data.International journal of molecular sciences · 2025Article
- Design, pharmacology, and toxicology of a novel chemically modified siRNA targeting hepatic angiotensinogen.Molecular therapy. Nucleic acids · 2025Article
- Preclinical evaluation of AGT mRNA replacement therapy for primary hyperoxaluria type I disease.Science advances · 2025Article
- Treatment of neurological pathology and inflammation in Machado-Joseph disease through in vivo self-assembled siRNA.Brain : a journal of neurology · 2025Article
- Cross-species RNAi therapy via AAV delivery alleviates neuropathic pain by targeting GCH1.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Article
- Development and evaluation of siRNA-mediated gene silencing strategies for ADO2 therapy utilizing iPSCs model and DMPC-SPIONs delivery system.Stem cell research & therapy · 2025Article
- The role of protein S-acylation in vascular injury associated with metabolic disorders.Frontiers in endocrinology · 2025Review
- siRMSD: A Structural Parameter to Reduce Sequence-Dependent Off-Target Effects for siRNA Design with Chemical Modifications.Methods in molecular biology (Clifton, N.J.) · 2025Article
- A Manual for Genome and Transcriptome Engineering.IEEE reviews in biomedical engineering · 2025Review
- Important Aspects of siRNA Design for Optimal Efficacy In Vitro and In Vivo.International journal of cell biology · 2025Review
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In RNA interference (RNAi), small interfering RNA (siRNA) suppresses the expression of its target mRNA with a perfect complementary sequence. In addition, siRNA also suppresses the expression of unintended mRNAs with partially complementary sequences mainly within the siRNA seed region (nucleotides 2-8). This mechanism is highly similar to microRNA (miRNA)-mediated RNA silencing, and known as the siRNA-mediated off-target effect. Previously, we revealed that the off-target effect is induced through stable base-pairing between the siRNA seed region and off-target mRNAs, but not induced through unstable base-pairing. However, in our recent study, we found that the siRNA seed region consists of two functionally different domains: nucleotides 2-5, essential for off-target effects, and nucleotides 6-8, involved in both RNAi and off-target effects. In this study, we investigated the most responsible region for the off-target effect by conducting a comprehensive analysis of the thermodynamic properties of all possible siRNA subregions that involved a machine learning technique using a random sampling procedure. As a result, the thermodynamic stability of nucleotides 2-5 showed the highest positive correlation with the off-target effect, and nucleotides 8-14 showed the most negative correlation. Thus, it is revealed that the siRNA off-target effect is determined by the base-pairing stabilities of two different subregions with opposite effects.
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Registered trials
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