ArticleJournal of RNAi and gene silencing : an international journal of RNA and gene targeting research2006
Minimizing off-target effects by using diced siRNAs for RNA interference.
Article in Journal of RNAi and gene silencing : an international journal of RNA and gene targeting research, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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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.
The trial behind it
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
22 citing papers in PubMed, 31 citations in OpenAlex.
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- Genome-scale single-cell mechanical phenotyping reveals disease-related genes involved in mitotic rounding.Nature communications · 2017Article
- Endothelial Cells Use a Formin-Dependent Phagocytosis-Like Process to Internalize the Bacterium Listeria monocytogenes.PLoS pathogens · 2016Article
- Properties of short double-stranded RNAs carrying randomized base pairs: toward better controls for RNAi experiments.RNA (New York, N.Y.) · 2015Article
- Modulation of flavivirus population diversity by RNA interference.Journal of virology · 2015Article
- siPools: highly complex but accurately defined siRNA pools eliminate off-target effects.Nucleic acids research · 2014Article
- Structure and function of steroid receptor RNA activator protein, the proposed partner of SRA noncoding RNA.Journal of molecular biology · 2014Article
- Production of highly potent recombinant siRNAs in Escherichia coli.Nature protocols · 2013Article
- High-throughput RNA interference screens integrative analysis: Towards a comprehensive understanding of the virus-host interplay.World journal of virology · 2013Review
- Maternally recruited DCP1A and DCP2 contribute to messenger RNA degradation during oocyte maturation and genome activation in mouse.Biology of reproduction · 2013Article
- Single-pot enzymatic synthesis of Dicer-substrate siRNAs.Nucleic acids research · 2012Article
- From RNAi screens to molecular function in embryonic stem cells.Stem cell reviews and reports · 2012Review
- Combined RNAi and localization for functionally dissecting long noncoding RNAs.Nature methods · 2012Article
- Genetic variation in radiation-induced cell death.Genome research · 2012Article
- Development of Therapeutic-Grade Small Interfering RNAs by Chemical Engineering.Frontiers in genetics · 2012Article
- Vigilance and validation: Keys to success in RNAi screening.ACS chemical biology · 2011Review
- The roles of cyclin A2, B1, and B2 in early and late mitotic events.Molecular biology of the cell · 2010Article
- Polymorphic cis- and trans-regulation of human gene expression.PLoS biology · 2010Article
- Silencing potential of viral derived RNAi constructs in Tomato leaf curl virus-AC4 gene suppression in tomato.Transgenic research · 2010Article
- Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Microarray studies have shown that individual synthetic small interfering RNAs (siRNAs) can have substantial off-target effects. Pools of siRNAs, produced by incubation of dsRNAs with recombinant Dicer or RNase III, can also be used to silence genes. Here we show that diced siRNA pools are highly complex, containing hundreds of different individual siRNAs. This high complexity could either compound the problem of off-target effects, since the number of potentially problematic siRNAs is high, or it could diminish the problem, since the concentration of any individual problematic siRNA is low. We therefore compared the off-target effects of diced siRNAs to chemically synthesized siRNAs. In agreement with previous reports, we found that two chemically synthesized siRNAs targeted against p38alpha MAPK (MAPK14) induced off-target changes in the abundance of hundreds of mRNAs. In contrast, three diced siRNA pools against p38alpha MAPK had almost no off-target effects. The off-target effects of a synthetic siRNA were reduced when the siRNA was diluted 3-fold in a diced pool and completely alleviated when it was diluted 30- or 300-fold, suggesting that when problematic siRNAs are present within a diced pool, their absolute concentration is too low to result in significant off-target effects. These data rationalize the observed high specificity of RNA interference in C. elegans and D. melanogaster, where gene suppression is mediated by endogenously-generated diced siRNA pools, and provide a strategy for improving the specificity of RNA interference experiments and screens in mammalian cells.
Indexed as
Identifiers
19771225PMC2737221W1483274944What OpenQuestion holds
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.