ArticleMolecular therapy. Nucleic acids2013
5' Unlocked Nucleic Acid Modification Improves siRNA Targeting.
Article in Molecular therapy. Nucleic acids, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
30 citing papers in PubMed, 65 citations in OpenAlex.
- The Versatile Applications of Antisense Oligonucleotides in Modern Medicine.International journal of molecular sciences · 2026Review
- Taming the Achilles' Heel: A Chemical and Structural Design to Address Off-Target Effects in siRNA Therapeutics.JACS Au · 2026Article
- Small Interfering RNA Carriers for Oncotherapy: A Preclinical Overview.Pharmaceutics · 2025Review
- Modified unlocked nucleic acid (MUNA) mitigates off-target effects of small interfering RNAs.Nucleic acids research · 2025Article
- Therapeutic Approaches of Viral Gene Silencing by Small Interfering RNA: Strategies to Prevent the Emergence of Antiviral Resistant Escape Mutants.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Targeting CIDEB alleviates liver steatosis and fibrosis in mouse MASH models.Molecular therapy. Nucleic acids · 2025Article
- Landscape of small nucleic acid therapeutics: moving from the bench to the clinic as next-generation medicines.Signal transduction and targeted therapy · 2025Review
- Nucleic acid drugs: recent progress and future perspectives.Signal transduction and targeted therapy · 2024Review
- Optimized allele-specific silencing of the dominant-negativeMolecular therapy. Nucleic acids · 2024Article
- Small interfering RNA (siRNA)-based therapeutic applications against viruses: principles, potential, and challenges.Journal of biomedical science · 2023Review
- Gene therapy for pediatric genetic kidney diseases.Pediatric discovery · 2023Review
- Noncoding RNA therapeutics for substance use disorder.Advances in drug and alcohol research · 2022Article
- Development and application of ribonucleic acid therapy strategies against COVID-19.International journal of biological sciences · 2022Review
- The development and improvement of ribonucleic acid therapy strategies.Molecular therapy. Nucleic acids · 2021Review
- Selective suppression of polyglutamine-expanded protein by lipid nanoparticle-delivered siRNA targeting CAG expansions in the mouse CNS.Molecular therapy. Nucleic acids · 2021Article
- siRNA Therapeutics: Future Promise for Neurodegenerative Diseases.Current neuropharmacology · 2021Review
- Overcoming Barriers for siRNA Therapeutics: From Bench to Bedside.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Amide-Modified RNA: Using Protein Backbone to Modulate Function of Short Interfering RNAs.Accounts of chemical research · 2020Article
- Investigation of Strand-Selective Interaction of SNA-Modified siRNA with AGO2-MID.International journal of molecular sciences · 2020Article
- Key Mechanistic Principles and Considerations Concerning RNA Interference.Frontiers in plant science · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Optimization of small interfering RNAs (siRNAs) is important in RNA interference (RNAi)-based therapeutic development. Some specific chemical modifications can control which siRNA strand is selected by the RNA-induced silencing complex (RISC) for gene silencing. Intended strand selection will increase potency and reduce off-target effects from the unintended strand. Sometimes, blocking RISC loading of the unintended strand leads to improved intended strand-silencing potency, but the generality of this phenomenon is unclear. Specifically, unlocked nucleic acid (UNA) modification of the 5' end of canonical (i.e., 19+2) siRNAs abrogates gene silencing of the modified strand, but the fate and potency of the unmodified strand has not been investigated. Here, we show that 5' UNA-modified siRNAs show improved silencing potency of the unmodified strand. We harness this advantageous property in a therapeutic context, where a limited target region in a conserved HIV 5' long terminal repeat U5 region would otherwise yield siRNAs with undesired strand selection properties and poor silencing. Applying 5' UNA modification to the unintended sense (S) strand of these otherwise poorly targeted siRNAs dramatically improves on-target silencing by the intended antisense (AS) strand in pNL4-3.luciferase studies. This study highlights the utility of 5' UNA siRNA modification in therapeutic contexts where siRNA sequence selection is constrained.Molecular Therapy-Nucleic Acids (2013) 2, e103; doi:10.1038/mtna.2013.36; published online 2 July 2013.
Identifiers
What OpenQuestion holds
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.