ArticleNucleic acids research2003
The activity of siRNA in mammalian cells is related to structural target accessibility: a comparison with antisense oligonucleotides.
Article in Nucleic acids research, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 104 papers, 1 of them a synthesis that pooled it.
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Who cites it
104 citing papers in PubMed, 1 synthesis or guideline pooled it, 290 citations in OpenAlex.
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- Systematic Screening, Rational Development, and Initial Optimization of Efficacious RNA Silencing Agents for Human Rod Opsin Therapeutics.Translational vision science & technology · 2019Article
- Functional Prediction of Candidate MicroRNAs for CRC Management Using in Silico Approach.International journal of molecular sciences · 2019Article
- Design of Peptidomimetic Functionalized Cholesterol Based Lipid Nanoparticles for Efficient Delivery of Therapeutic Nucleic Acids.Molecules (Basel, Switzerland) · 2019Article
- LncRNA IMFNCR Promotes Intramuscular Adipocyte Differentiation by Sponging miR-128-3p and miR-27b-3p.Frontiers in genetics · 2019Article
- Strategies for Improving siRNA-Induced Gene Silencing Efficiency.Advanced pharmaceutical bulletin · 2017Article
- Preclinical Evaluation of a Lentiviral Vector for Huntingtin Silencing.Molecular therapy. Methods & clinical development · 2017Article
- Association genetics in Populus reveals the interactions between Pto-miR160a and its target Pto-ARF16.Molecular genetics and genomics : MGG · 2016Article
- Cellular localization of long non-coding RNAs affects silencing by RNAi more than by antisense oligonucleotides.Nucleic acids research · 2016Article
- Structural Dynamics of Human Argonaute2 and Its Interaction with siRNAs Designed to Target Mutant tdp43.Advances in bioinformatics · 2016Article
- RNAi revised--target mRNA-dependent enhancement of gene silencing.Nucleic acids research · 2015Article
- Association genetics in Populus reveals the interactions between Pt-miR397a and its target genes.Scientific reports · 2015Article
- Silencing efficacy prediction: a retrospective study on target mRNA features.Bioscience reports · 2015Article
44 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The biological activity of siRNA seems to be influenced by local characteristics of the target RNA, including local RNA folding. Here, we investigated quantitatively the relationship between local target accessibility and the extent of inhibition of the target gene by siRNA. Target accessibility was assessed by a computational approach that had been shown earlier to be consistent with experimental probing of target RNA. Two sites of ICAM-1 mRNA predicted to serve as accessible motifs and one site predicted to adopt an inaccessible structure were chosen to test siRNA constructs for suppression of ICAM-1 gene expression in ECV304 cells. The local target-dependent effectiveness of siRNA was compared with antisense oligonucleotides (asON). The concentration dependency of siRNA-mediated suppression indicates a >1000-fold difference between active siRNAs (IC50 approximately 0.2-0.5 nM) versus an inactive siRNA (IC50 > or = 1 microM) which is consistent with the activity pattern of asON when relating target suppression to predicted local target accessibility. The extremely high activity of the siRNA si2B (IC50 = 0.24 nM) indicates that not all siRNAs shown to be active at the usual concentrations of >10-100 nM belong to this highly active species. The observations described here suggest an option to assess target accessibility for siRNA and, thus, support the design of active siRNA constructs. This approach can be automated, work at high throughput and is open to include additional parameters relevant to the biological activity of siRNA.
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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.