ArticleNucleic acids research2020
Effect of 2'-5'/3'-5' phosphodiester linkage heterogeneity on RNA interference.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 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
12 citing papers in PubMed, 24 citations in OpenAlex.
- Synthesis of siRNAs containing carbocyclic nucleotides and the role of cyclopentane conformation in RNAi activity.RSC chemical biology · 2026Article
- Acyclic serinol nucleic acid modification of siRNAs overcomes seed region mediated off-target effects while maintaining potency.Nucleic acids research · 2026Article
- The XNA alphabet.Nucleic acids research · 2025Review
- Enhancing Gene Delivery to Breast Cancer with Highly Efficient siRNA Loading and pH-Responsive Small Extracellular Vesicles.ACS biomaterials science & engineering · 2025Article
- 2'-ACS medicinal chemistry letters · 2024Article
- RNA-protein complexes and force field polarizability.Frontiers in chemistry · 2023Article
- Inhaled siRNA Formulations for Respiratory Diseases: From Basic Research to Clinical Application.Pharmaceutics · 2022Review
- Gene editing with CRISPR-Cas12a guides possessing ribose-modified pseudoknot handles.Nature communications · 2021Article
- Site-specific Incorporation of 2',5'-Linked Nucleic Acids Enhances Therapeutic Profile of Antisense Oligonucleotides.ACS medicinal chemistry letters · 2021Article
- Triazole-Modified Nucleic Acids for the Application in Bioorganic and Medicinal Chemistry.Biomedicines · 2021Review
- Chemical strategies for strand selection in short-interfering RNAs.RSC advances · 2021Review
- Hybrid DNA/RNA nanostructures with 2'-5' linkages.Nanoscale · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
We report on the synthesis of siRNAs containing both 2'-5'- and 3'-5'-internucleotide linkages and their effects on siRNA structure, function, and interaction with RNAi proteins. Screening of these siRNAs against their corresponding mRNA targets showed that 2'-5' linkages were well tolerated in the sense strand, but only at a few positions in the antisense strand. Extensive modification of the antisense strand minimally affected 5'-phosphorylation of the siRNA by kinases, however, it negatively affected siRNA loading into human AGO2. Modelling and molecular dynamics simulations were fully consistent with these findings. Furthermore, our studies indicated that the presence of a single 5'p-rN1-(2'-5')-N2 unit in the antisense strand does not alter the 'clover leaf' bend and sugar puckers that are critical for anchoring the 5'-phosphate to Ago 2 MID domain. Importantly, 2'-5'-linkages had the added benefit of abrogating immune-stimulatory activity of siRNAs. Together, these results demonstrate that 2'-5'/3'-5'-modified siRNAs, when properly designed, can offer an efficient new class of siRNAs with diminished immune-stimulatory responses.
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.