ArticleNucleic acids research2017
siRNA carrying an (E)-vinylphosphonate moiety at the 5΄ end of the guide strand augments gene silencing by enhanced binding to human Argonaute-2.
Article in Nucleic acids research, 2017. 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 48 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
48 citing papers in PubMed.
- RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026Review
- 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
- A novel bispecific siRNA concept: Efficient dual knockdown ofMolecular therapy. Nucleic acids · 2025Article
- Potent and durable gene modulation in heart and muscle with chemically defined lipophilic siRNAs.Nucleic acids research · 2025Article
- Optimized chemical structure extends silencing duration of therapeutic siRNAs in dividing cancer and immune cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- RNA chemistry and therapeutics.Nature reviews. Drug discovery · 2025Review
- Small Interfering RNA Carriers for Oncotherapy: A Preclinical Overview.Pharmaceutics · 2025Review
- A potent GalNAc-siRNA drug, RBD1016, leads to sustained HBsAg reduction and seroconversion in mouse models of HBV infection.Molecular therapy. Nucleic acids · 2025Article
- Redesigning miR-34a: structural and chemical advances in the therapeutic development of an miRNA anti-cancer agent.Biochemical Society transactions · 2025Article
- Single alkyl phosphonate modification of the siRNA backbone in the seed region enhances specificity and therapeutic profile.Nucleic acids research · 2025Article
- Enhancing siRNA efficacy in vivo with extended nucleic acid backbones.Nature biotechnology · 2025Article
- Design, Screening and Development of Asymmetric siRNAs Targeting theBiomolecules & therapeutics · 2025Article
- Important Aspects of siRNA Design for Optimal Efficacy In Vitro and In Vivo.International journal of cell biology · 2025Review
- The beauty of symmetry: siRNA phosphorodithioate modifications reduce stereocomplexity, ease analysis, and can improveMolecular therapy. Nucleic acids · 2024Article
- RNAi-based drug design: considerations and future directions.Nature reviews. Drug discovery · 2024Review
- Targeting RNA with synthetic oligonucleotides: Clinical success invites new challenges.Cell chemical biology · 2024Review
- RNA-based medicine: from molecular mechanisms to therapy.The EMBO journal · 2023Review
- Amplifying gene expression with RNA-targeted therapeutics.Nature reviews. Drug discovery · 2023Review
- Chemistry, structure and function of approved oligonucleotide therapeutics.Nucleic acids research · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
7 authors.
Funding
Abstract
Efficient gene silencing by RNA interference (RNAi) in vivo requires the recognition and binding of the 5΄- phosphate of the guide strand of an siRNA by the Argonaute protein. However, for exogenous siRNAs it is limited by the rapid removal of the 5΄- phosphate of the guide strand by metabolic enzymes. Here, we have determined the crystal structure of human Argonaute-2 in complex with the metabolically stable 5΄-(E)-vinylphosphonate (5΄-E-VP) guide RNA at 2.5-Å resolution. The structure demonstrates how the 5΄ binding site in the Mid domain of human Argonaute-2 is able to adjust the key residues in the 5΄-nucleotide binding pocket to compensate for the change introduced by the modified nucleotide. This observation also explains improved binding affinity of the 5΄-E-VP -modified siRNA to human Argonaute-2 in-vitro, as well as the enhanced silencing in the context of the trivalent N-acetylgalactosamine (GalNAc)-conjugated siRNA in mice relative to the un-modified siRNA.
Indexed as
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.