ArticleMolecular therapy. Nucleic acids2017
Site-Specific Modification Using the 2'-Methoxyethyl Group Improves the Specificity and Activity of siRNAs.
Article in Molecular therapy. Nucleic acids, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 49 citations in OpenAlex.
- Research progress and development strategies of antibody-oligonucleotide conjugates.Gene therapy · 2026Review
- Advances in nano-delivery systems for overcoming the challenges of applying siRNA drugs in tumor therapy.Asian journal of pharmaceutical sciences · 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
- Two-Stage Probability-Enhanced Regression on Property Matrices and LLM Embeddings Enables State-of-the-Art Prediction of Gene Knockdown by Modified siRNAs.International journal of molecular sciences · 2025Article
- The functions of circular RNAs and long noncoding RNAs in cholangiocarcinoma.Discover oncology · 2025Review
- Small Interfering RNA Carriers for Oncotherapy: A Preclinical Overview.Pharmaceutics · 2025Review
- Discovery of long-acting APOC3 siRNA for treating patients with hypertriglyceridemia.Nucleic acids research · 2025Article
- Trends and Commonalities of Approved and Late Clinical-Phase RNA Therapeutics.Pharmaceutics · 2025Review
- Systematic Evaluation of Position-Specific Tolerability of Seven Backbone and Ribose Modifications in Fully Chemically Stabilized siRNAs.Nucleic acid therapeutics · 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
- A Manual for Genome and Transcriptome Engineering.IEEE reviews in biomedical engineering · 2025Review
- Chemical Modifications in Nucleic Acid Therapeutics.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Oligonucleotide therapeutics in sports? An antidoping perspective.Archiv der Pharmazie · 2025Review
- Optimized RNA interference therapeutics combined with interleukin-2 mRNA for treating hepatitis B virus infection.Signal transduction and targeted therapy · 2024Article
- Oligonucleotide therapies for nonalcoholic steatohepatitis.Molecular therapy. Nucleic acids · 2024Review
- Updates in Small Interfering RNA for the Treatment of Dyslipidemias.Current atherosclerosis reports · 2023Review
- Innate immune regulations and various siRNA modalities.Drug delivery and translational research · 2023Review
- Small interfering RNA (siRNA)-based therapeutic applications against viruses: principles, potential, and challenges.Journal of biomedical science · 2023Review
- Enhancing the Effectiveness of Oligonucleotide Therapeutics Using Cell-Penetrating Peptide Conjugation, Chemical Modification, and Carrier-Based Delivery Strategies.Pharmaceutics · 2023Review
- Targeting ANGPTL3 by GalNAc-conjugated siRNAMolecular therapy. Nucleic acids · 2023Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Rapid progress has been made toward small interfering RNA (siRNA)-based therapy for human disorders, but rationally optimizing siRNAs for high specificity and potent silencing remains a challenge. In this study, we explored the effect of chemical modification at the cleavage site of siRNAs. We found that modifications at positions 9 and 10 markedly reduced the silencing potency of the unmodified strand of siRNAs but were well tolerated by the modified strand. Intriguingly, addition of the 2'-methoxyethyl (MOE) group at the cleavage site improved both the specificity and silencing activity of siRNAs by facilitating the oriented RNA-induced silencing complex (RISC) loading of the modified strand. Furthermore, we combined MOE modifications at positions 9 and 10 of one strand together with 2'-O-methylation (OMe) at position 14 of the other strand and found a synergistic effect that improved the specificity of siRNAs. The surprisingly beneficial effect of the combined modification was validated using siRNA-targeting endogenous gene intercellular adhesion molecule 1 (ICAM1). We found that the combined modifications eliminated its off-target effects. In conclusion, we established effective strategies to optimize siRNAs using site-specific MOE modifications. The findings may allow the creation of superior siRNAs for therapy in terms of activity and specificity.
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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.