ArticleNucleic acids research2015
Identification of metabolically stable 5'-phosphate analogs that support single-stranded siRNA activity.
Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 39 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
39 citing papers in PubMed, 95 citations in OpenAlex.
- Article
- Synthesis of siRNAs containing carbocyclic nucleotides and the role of cyclopentane conformation in RNAi activity.RSC chemical biology · 2026Article
- Organyl 5'-Phosphates in siRNA Guide Strands: Structure-Function Relationships Governing Anchoring in Argonaute 2 and Metabolic Stability.bioRxiv : the preprint server for biology · 2026Article
- Advances in nano-delivery systems for overcoming the challenges of applying siRNA drugs in tumor therapy.Asian journal of pharmaceutical sciences · 2026Review
- RNA-based therapeutic opportunities for the treatment of kidney diseases.Nature reviews. Nephrology · 2026Review
- Discovery of long-acting APOC3 siRNA for treating patients with hypertriglyceridemia.Nucleic acids research · 2025Article
- Redesigning miR-34a: structural and chemical advances in the therapeutic development of an miRNA anti-cancer agent.Biochemical Society transactions · 2025Article
- Improving the potency prediction for chemically modified siRNAs through insights from molecular modeling of individual sequence positions.Molecular therapy. Nucleic acids · 2025Article
- Oligonucleotide therapeutics in sports? An antidoping perspective.Archiv der Pharmazie · 2025Review
- Chemical Modifications in Nucleic Acid Therapeutics.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Important Aspects of siRNA Design for Optimal Efficacy In Vitro and In Vivo.International journal of cell biology · 2025Review
- Structure-Activity Relationship of Antibody-Oligonucleotide Conjugates: Evaluating Bioconjugation Strategies for Antibody-siRNA Conjugates for Drug Development.Journal of medicinal chemistry · 2024Article
- A Visual Compendium of Principal Modifications within the Nucleic Acid Sugar Phosphate Backbone.Molecules (Basel, Switzerland) · 2024Review
- Oligonucleotide therapies for nonalcoholic steatohepatitis.Molecular therapy. Nucleic acids · 2024Review
- Frameworks for transformational breakthroughs in RNA-based medicines.Nature reviews. Drug discovery · 2024Review
- RNAi-based drug design: considerations and future directions.Nature reviews. Drug discovery · 2024Review
- RNA interference in the era of nucleic acid therapeutics.Nature biotechnology · 2024Review
- RNA-based medicine: from molecular mechanisms to therapy.The EMBO journal · 2023Review
- Chemistry, structure and function of approved oligonucleotide therapeutics.Nucleic acids research · 2023Review
- Structural Modifications of siRNA Improve Its Performance In Vivo.International journal of molecular sciences · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The ss-siRNA activity in vivo requires a metabolically stable 5'-phosphate analog. In this report we used crystal structure of the 5'-phosphate binding pocket of Ago-2 bound with guide strand to design and synthesize ss-siRNAs containing various 5'-phosphate analogs. Our results indicate that the electronic and spatial orientation of the 5'-phosphate analog was critical for ss-siRNA activity. Chemically modified ss-siRNA targeting human apoC III mRNA demonstrated good potency for inhibiting ApoC III mRNA and protein in transgenic mice. Moreover, ApoC III ss-siRNAs were able to reduce the triglyceride and LDL cholesterol in transgenic mice demonstrating pharmacological effect of ss-siRNA. Our study provides guidance to develop surrogate phosphate analog for ss-siRNA and demonstrates that ss-siRNA provides an alternative strategy for therapeutic gene silencing.
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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.