ArticleRNA (New York, N.Y.)2021
Mechanistic analysis of the enhanced RNAi activity by 6-mCEPh-purine at the 5' end of the siRNA guide strand.
Article in RNA (New York, N.Y.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 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
4 citing papers in PubMed, 7 citations in OpenAlex.
- 5'-end uridine-derived base modification for siRNAs potency reinforcement.Cell & bioscience · 2026Article
- A Computational Approach for Designing and Validating Small Interfering RNA against SARS-CoV-2 Variants.Current computer-aided drug design · 2024Article
- Review
- siRNA potency enhancement via chemical modifications of nucleotide bases at the 5'-end of the siRNA guide strand.RNA (New York, N.Y.) · 2021Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A key approach for improving siRNA efficacy is chemical modifications. Through an in silico screening of modifications at the 5'-end nucleobase of the guide strand, an adenine-derived compound called 6-(3-(2-carboxyethyl)phenyl)-purine (6-mCEPh-purine) was identified to improve the RNAi activity in cultured human cells and in vivo mouse models. Nevertheless, it remains unclear how this chemical modification enhances the siRNA potency. Here, we used a series of biochemical approaches to quantitatively evaluate the effect of the 6-mCEPh-purine modification at each step in the assembly of the RNAi effector complex called RISC. We found that the modification improves the formation of mature RISC at least in two different ways, by fixing the loading orientation of siRNA duplexes and increasing the stability of mature RISC after passenger strand ejection. Our data will provide a molecular platform for further development of chemically modified siRNA drugs.
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