ArticleACS chemical biology2018
A Single Amide Linkage in the Passenger Strand Suppresses Its Activity and Enhances Guide Strand Targeting of siRNAs.
Article in ACS chemical biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
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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
18 citing papers in PubMed, 28 citations in OpenAlex.
- Review
- 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
- Nucleic acid therapeutics in neurodegenerative disorders: emerging technologies and clinical landscape.Molecular neurodegeneration advances · 2026Review
- Enhancing siRNA efficacy in vivo with extended nucleic acid backbones.Nature biotechnology · 2025Article
- Amide Internucleoside Linkages Suppress the MicroRNA-like Off-Target Activity of Short Interfering RNA.ACS chemical biology · 2025Article
- Synthesis and Properties of RNA Modified with Thioamide Internucleoside Linkage.Chembiochem : a European journal of chemical biology · 2024Article
- Synthesis and Properties of RNA Modified with Cationic Amine Internucleoside Linkage.ACS chemical biology · 2024Article
- Chemistry, structure and function of approved oligonucleotide therapeutics.Nucleic acids research · 2023Review
- Amide Modifications in the Seed Region of the Guide Strand Improve the On-Target Specificity of Short Interfering RNA.ACS chemical biology · 2023Article
- Chemical Modifications of CRISPR RNAs to Improve Gene-Editing Activity and Specificity.Journal of the American Chemical Society · 2022Review
- An LNA-amide modification that enhances the cell uptake and activity of phosphorothioate exon-skipping oligonucleotides.Nature communications · 2022Article
- Optimization of Automated Synthesis of Amide-Linked RNA.ACS omega · 2022Article
- Amide Internucleoside Linkages Are Well Tolerated in Protospacer Adjacent Motif-Distal Region of CRISPR RNAs.ACS chemical biology · 2022Article
- Chemical strategies for strand selection in short-interfering RNAs.RSC advances · 2021Review
- Beyond ribose and phosphate: Selected nucleic acid modifications for structure-function investigations and therapeutic applications.Beilstein journal of organic chemistry · 2021Review
- Amide-Modified RNA: Using Protein Backbone to Modulate Function of Short Interfering RNAs.Accounts of chemical research · 2020Article
- Synthesis and Evaluation of Neutral Phosphate Triester Backbone-Modified siRNAs.ACS medicinal chemistry letters · 2020Article
- Synthesis and Biological Activity of Short Interfering RNAs Having Several Consecutive Amide Internucleoside Linkages.Chemistry (Weinheim an der Bergstrasse, Germany) · 2020Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Potential in vivo applications of RNA interference (RNAi) require suppression of various off-target activities. Herein, we report that replacement of a single phosphate linkage between the first and second nucleosides of the passenger strand with an amide linkage almost completely abolished its undesired activity and restored the desired activity of guide strands that had been compromised by unfavorable amide modifications. Molecular modeling suggested that the observed effect was most likely due to suppressed loading of the amide-modified strand into Ago2 caused by inability of amide to adopt the conformation required for the backbone twist that docks the first nucleotide of the guide strand in the MID domain of Ago2. Eliminating off-target activity of the passenger strand will be important for improving therapeutic potential of RNAi.
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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.