ArticleNucleic acids research2011
Unexpected origins of the enhanced pairing affinity of 2'-fluoro-modified RNA.
Article in Nucleic acids research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 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
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Who cites it
90 citing papers in PubMed, 192 citations in OpenAlex.
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- Conjugation of hydrophobic drugs to motile pRNA 4WJ nanoparticles for spontaneous tumor targeting and undetectable toxicity.Nature protocols · 2026Review
- 5'-Palmitate Lipid and Internal LNA-Piperidyl Triesters Enhance the RNA Affinity and Activity of Splice-Switching Oligonucleotides.Journal of the American Chemical Society · 2026Article
- Evolution of siRNA Therapeutics: From Mechanistic Foundations to Clinical Expansion.Pharmaceutics · 2026Review
- Direct targeting of C9ORF72 repeat RNA with fluorinated antisense oligonucleotides.Nucleic acids research · 2026Article
- 2'-Ribose-modified nucleotides: A strategy for reducing off-target effects of oligonucleotide drugs.Molecular therapy. Nucleic acids · 2026Article
- A Modular DNAzyme for Precise Visualization and Intervention of Alternative Splicing Isoforms in Live Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Advances and challenges in non-canonical nucleic acids data storage.Nature communications · 2026Review
- A modified X10-23 DNAzyme that can better access large, structured RNA targets.Nucleic acids research · 2026Article
- Functional Relevance of CASP16 Nucleic Acid Predictions as Evaluated by Structure Providers.Proteins · 2026Article
- Biophysical and biological properties of splice-switching oligonucleotides and click conjugates containing LNA-phosphothiotriester linkages.Nucleic acids research · 2025Article
- Analysis of the Effects of Sugar Modifications on RNA Chemical Ligation Reactions.Chembiochem : a European journal of chemical biology · 2025Article
- Small Interfering RNA Carriers for Oncotherapy: A Preclinical Overview.Pharmaceutics · 2025Review
- Stereo-random oligonucleotides enable efficient recruitment of ADAR in vitro and in vivo.Nature communications · 2025Article
- Modified unlocked nucleic acid (MUNA) mitigates off-target effects of small interfering RNAs.Nucleic acids research · 2025Article
- The Effect of 2'F-RNA on I-Motif Structure and Stability.Molecules (Basel, Switzerland) · 2025Article
- Pharmaceutical perspectives on oligonucleotide therapeutics and delivery systems.Pharmacological reviews · 2025Review
- Targeting Glioblastoma Stem Cells via EphA2: Structural Insights into the RNA Aptamer A40s for Precision Therapy.Journal of chemical information and modeling · 2025Article
- Functional relevance of CASP16 nucleic acid predictions as evaluated by structure providers.bioRxiv : the preprint server for biology · 2025Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Various chemical modifications are currently being evaluated for improving the efficacy of short interfering RNA (siRNA) duplexes as antisense agents for gene silencing in vivo. Among the 2'-ribose modifications assessed to date, 2'deoxy-2'-fluoro-RNA (2'-F-RNA) has unique properties for RNA interference (RNAi) applications. Thus, 2'-F-modified nucleotides are well tolerated in the guide (antisense) and passenger (sense) siRNA strands and the corresponding duplexes lack immunostimulatory effects, enhance nuclease resistance and display improved efficacy in vitro and in vivo compared with unmodified siRNAs. To identify potential origins of the distinct behaviors of RNA and 2'-F-RNA we carried out thermodynamic and X-ray crystallographic analyses of fully and partially 2'-F-modified RNAs. Surprisingly, we found that the increased pairing affinity of 2'-F-RNA relative to RNA is not, as commonly assumed, the result of a favorable entropic contribution ('conformational preorganization'), but instead primarily based on enthalpy. Crystal structures at high resolution and osmotic stress demonstrate that the 2'-F-RNA duplex is less hydrated than the RNA duplex. The enthalpy-driven, higher stability of the former hints at the possibility that the 2'-substituent, in addition to its important function in sculpting RNA conformation, plays an underappreciated role in modulating Watson-Crick base pairing strength and potentially π-π stacking interactions.
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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.