ArticleRNA (New York, N.Y.)2006
Position-specific chemical modification of siRNAs reduces "off-target" transcript silencing.
Article in RNA (New York, N.Y.), 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 340 papers.
What it found
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Who cites it
340 citing papers in PubMed, 782 citations in OpenAlex.
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- Antibody-oligonucleotide conjugates: design principles, intracellular delivery, and translational opportunities.Journal of hematology & oncology · 2026Review
- DNA Nanostructures for siRNA Delivery.Bioconjugate chemistry · 2026Review
- miRNA-lncRNA Cross-Regulation Landscape in Cancer: From Molecular Mechanisms to Therapeutic and Diagnostic Applications.Cancers · 2026Review
- A Long-Term Human Liver Spheroid Model for Assessing Silencing and Durability of GalNAc-Conjugated siRNAs.Clinical and translational science · 2026Article
- Long-Acting RNA Interference Therapies for Cardiovascular Risk Reduction: Current Evidence and Emerging Targets.Current cardiology reports · 2026Review
- Taming the Achilles' Heel: A Chemical and Structural Design to Address Off-Target Effects in siRNA Therapeutics.JACS Au · 2026Article
- Omega Nucleic Acids (ΩNA), Ultimate Nucleic Acids for Future Technology.Molecules (Basel, Switzerland) · 2026Review
- Advances in nano-delivery systems for overcoming the challenges of applying siRNA drugs in tumor therapy.Asian journal of pharmaceutical sciences · 2026Review
- Respiratory Delivery of Highly Conserved Antiviral siRNAs Suppress SARS-CoV-2 Infection.International journal of molecular sciences · 2025Article
- Discovery of long-acting APOC3 siRNA for treating patients with hypertriglyceridemia.Nucleic acids research · 2025Article
- Single alkyl phosphonate modification of the siRNA backbone in the seed region enhances specificity and therapeutic profile.Nucleic acids research · 2025Article
- Pharmaceutical perspectives on oligonucleotide therapeutics and delivery systems.Pharmacological reviews · 2025Review
- Rapid and robust validation of pooled CRISPR knockout screens using CelFi.Scientific reports · 2025Article
- Thermodynamic Parameter Estimation for Modified Oligonucleotides Using Molecular Dynamics Simulations.The journal of physical chemistry. B · 2025Article
- Amide Internucleoside Linkages Suppress the MicroRNA-like Off-Target Activity of Short Interfering RNA.ACS chemical biology · 2025Article
- Important Aspects of siRNA Design for Optimal Efficacy In Vitro and In Vivo.International journal of cell biology · 2025Review
- Chemical Strategies to Enhance Antisense Strand Selection and Minimize Off-Target Effect-Mediated by siRNAs.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Chemical Modifications in Nucleic Acid Therapeutics.Methods in molecular biology (Clifton, N.J.) · 2025Review
280 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Transfected siRNAs regulate numerous transcripts sharing limited complementarity to the RNA duplex. This unintended ("off-target") silencing can hinder the use of RNAi to define gene function. Here we describe position-specific, sequence-independent chemical modifications that reduced silencing of partially complementary transcripts by all siRNAs tested. Silencing of perfectly matched targets was unaffected by these modifications. The chemical modification also reduced off-target phenotypes in growth inhibition studies. Key to the modification was 2'-O-methyl ribosyl substitution at position 2 in the guide strand, which reduced silencing of most off-target transcripts with complementarity to the seed region of the siRNA guide strand. The sharp position dependence of 2'-O-methyl ribosyl modification contrasts with the broader position dependence of base-pair substitutions within the seed region, suggesting a role for position 2 of the guide strand distinct from its effects on pairing to target transcripts.
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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.