ArticleNucleic acids research2014
Amides are excellent mimics of phosphate internucleoside linkages and are well tolerated in short interfering RNAs.
Article in Nucleic acids research, 2014. 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 31 papers.
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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.
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Who cites it
31 citing papers in PubMed, 60 citations in OpenAlex.
- Review
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- 5'-end uridine-derived base modification for siRNAs potency reinforcement.Cell & bioscience · 2026Article
- Biophysical and biological properties of splice-switching oligonucleotides and click conjugates containing LNA-phosphothiotriester linkages.Nucleic acids research · 2025Article
- From liquid-phase synthesis to chemical ligation: preparation of oligonucleotides and their backbone analogs in solution.Nucleic acids research · 2025Review
- Single alkyl phosphonate modification of the siRNA backbone in the seed region enhances specificity and therapeutic profile.Nucleic acids research · 2025Article
- Landscape of small nucleic acid therapeutics: moving from the bench to the clinic as next-generation medicines.Signal transduction and targeted therapy · 2025Review
- 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
- Origin of ribonucleotide recognition motifs through ligand mimicry at early earth.RNA biology · 2024Review
- Amide Modifications in the Seed Region of the Guide Strand Improve the On-Target Specificity of Short Interfering RNA.ACS chemical biology · 2023Article
- Optimization of Automated Synthesis of Amide-Linked RNA.ACS omega · 2022Article
- SiRNAs with Neutral Phosphate Triester Hydrocarbon Tails Exhibit Carrier-Free Gene-Silencing Activity.ACS medicinal chemistry letters · 2022Article
- Amide Internucleoside Linkages Are Well Tolerated in Protospacer Adjacent Motif-Distal Region of CRISPR RNAs.ACS chemical biology · 2022Article
- Modified internucleoside linkages for nuclease-resistant oligonucleotides.RSC chemical biology · 2021Review
- Beyond ribose and phosphate: Selected nucleic acid modifications for structure-function investigations and therapeutic applications.Beilstein journal of organic chemistry · 2021Review
- Towards Zwitterionic Oligonucleotides with Improved Properties: the NAA/LNA-Gapmer Approach.Chembiochem : a European journal of chemical biology · 2020Article
- 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
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
RNA interference (RNAi) has become an important tool in functional genomics and has an intriguing therapeutic potential. However, the current design of short interfering RNAs (siRNAs) is not optimal for in vivo applications. Non-ionic phosphate backbone modifications may have the potential to improve the properties of siRNAs, but are little explored in RNAi technologies. Using X-ray crystallography and RNAi activity assays, the present study demonstrates that 3'-CH2-CO-NH-5' amides are excellent replacements for phosphodiester internucleoside linkages in RNA. The crystal structure shows that amide-modified RNA forms a typical A-form duplex. The amide carbonyl group points into the major groove and assumes an orientation that is similar to the P-OP2 bond in the phosphate linkage. Amide linkages are well hydrated by tandem waters linking the carbonyl group and adjacent phosphate oxygens. Amides are tolerated at internal positions of both the guide and passenger strand of siRNAs and may increase the silencing activity when placed near the 5'-end of the passenger strand. As a result, an siRNA containing eight amide linkages is more active than the unmodified control. The results suggest that RNAi may tolerate even more extensive amide modification, which may be useful for optimization of siRNAs for in vivo applications.
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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.