ArticleACS chemical biology2023
Amide Modifications in the Seed Region of the Guide Strand Improve the On-Target Specificity of Short Interfering RNA.
Article in ACS chemical biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 11 citations in OpenAlex.
- Acyclic serinol nucleic acid modification of siRNAs overcomes seed region mediated off-target effects while maintaining potency.Nucleic acids research · 2026Article
- Advances in nano-delivery systems for overcoming the challenges of applying siRNA drugs in tumor therapy.Asian journal of pharmaceutical sciences · 2026Review
- Nucleic acid therapeutics in neurodegenerative disorders: emerging technologies and clinical landscape.Molecular neurodegeneration advances · 2026Review
- 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
- Amide Internucleoside Linkages Suppress the MicroRNA-like Off-Target Activity of Short Interfering RNA.ACS chemical biology · 2025Article
- Synthesis of 2'-formamidonucleoside phosphoramidites for suppressing the seed-based off-target effects of siRNAs.Nucleic acids research · 2024Article
- 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
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
RNA interference (RNAi) is a well-established research tool and is also maturing as a novel therapeutic approach. For the latter, microRNA-like off-target activity of short interfering RNAs (siRNAs) remains as one of the main problems limiting RNAi drug development. In this communication, we report that replacement of a single internucleoside phosphodiester in the seed region (nucleotides 2 to 7) of the guide strand with an amide linkage suppressed the undesired microRNA-like off-target activity by at least an order of magnitude. For the specific siRNA targeting the PIK3CB gene, an amide modification between the third and fourth nucleotides of the guide strand showed the strongest enhancement of specificity (completely eliminated off-target silencing) while maintaining high on-target activity. These results are important because off-target activity is one of the main remaining roadblocks for RNA based drug development.
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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 Socratic graph.