ArticlePloS one2011
Improved siRNA/shRNA functionality by mismatched duplex.
Article in PloS one, 2011. 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.
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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, 34 citations in OpenAlex.
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- Two-Stage Probability-Enhanced Regression on Property Matrices and LLM Embeddings Enables State-of-the-Art Prediction of Gene Knockdown by Modified siRNAs.International journal of molecular sciences · 2025Article
- Respiratory Delivery of Highly Conserved Antiviral siRNAs Suppress SARS-CoV-2 Infection.International journal of molecular sciences · 2025Article
- Chemical optimization of siRNA for safe and efficient silencing of placental sFLT1.Molecular therapy. Nucleic acids · 2022Article
- Engineering miRNA features into siRNAs: Guide-strand bulges are compatible with gene repression.Molecular therapy. Nucleic acids · 2022Article
- microRNA strand selection: Unwinding the rules.Wiley interdisciplinary reviews. RNA · 2021Review
- Beyond identity: Understanding the contribution of the 5' nucleotide of the antisense strand to RNAi activity.PloS one · 2021Article
- Systems biology-based investigation of cooperating microRNAs as monotherapy or adjuvant therapy in cancer.Nucleic acids research · 2019Review
- Site-Specific Modification Using the 2'-Methoxyethyl Group Improves the Specificity and Activity of siRNAs.Molecular therapy. Nucleic acids · 2017Article
- Dicer-independent processing of small RNA duplexes: mechanistic insights and applications.Nucleic acids research · 2017Review
- Recent advances in RNAi-based strategies for therapy and prevention of HIV-1/AIDS.Advanced drug delivery reviews · 2016Review
- Guidelines for the optimal design of miRNA-based shRNAs.Methods (San Diego, Calif.) · 2016Review
- Improved knockdown from artificial microRNAs in an enhanced miR-155 backbone: a designer's guide to potent multi-target RNAi.Nucleic acids research · 2016Article
- Modulation of the RNA Interference Activity Using Central Mismatched siRNAs and Acyclic Threoninol Nucleic Acids (aTNA) Units.Molecules (Basel, Switzerland) · 2015Article
- Multiplexing seven miRNA-Based shRNAs to suppress HIV replication.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- A screen for F1 hybrid male rescue reveals no major-effect hybrid lethality loci in the Drosophila melanogaster autosomal genome.G3 (Bethesda, Md.) · 2014Article
- Designing Ago2-specific siRNA/shRNA to Avoid Competition with Endogenous miRNAs.Molecular therapy. Nucleic acids · 2014Article
- siPools: highly complex but accurately defined siRNA pools eliminate off-target effects.Nucleic acids research · 2014Article
- Mg2+ effect on argonaute and RNA duplex by molecular dynamics and bioinformatics implications.PloS one · 2014Article
- Towards the elements of successful insect RNAi.Journal of insect physiology · 2013Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
siRNA (small interfering RNA) and shRNA (small hairpin RNA) are powerful and commonly used tools in biomedical research. Currently, siRNAs are generally designed as two 21 nt strands of RNA that include a 19 nt completely complementary part and a 2 nt overhang. However, since the si/shRNAs use the endogenous miRNA machinery for gene silencing and the miRNAs are generally 22 nt in length and contain multiple internal mismatches, we tested if the functionality can be increased by designing the si/shRNAs to mimic a miRNA structure. We systematically investigated the effect of single or multiple mismatches introduced in the passenger strand at different positions on siRNA functionality. Mismatches at certain positions could significantly increase the functionality of siRNAs and also, in some cases decreased the unwanted passenger strand functionality. The same strategy could also be used to design shRNAs. Finally, we showed that both si and miRNA structured oligos (siRNA with or without mismatches in the passenger strand) can repress targets in all individual Ago containing cells, suggesting that the Ago proteins do not differentiate between si/miRNA-based structure for silencing activity.
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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.