ArticleBMC bioinformatics2009
siDirect 2.0: updated software for designing functional siRNA with reduced seed-dependent off-target effect.
Article in BMC bioinformatics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers.
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117 citing papers in PubMed, 277 citations in OpenAlex.
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- Multiomics Reveals IL-17 Drives Epithelial Keratinization and Proliferation via EHF in Odontogenic Keratocysts.International journal of molecular sciences · 2026Article
- Molecular Dynamics Simulation-Assisted siRNA Design for Dual-Ubiquitinated SKP2 Silencing via Ago2 Anchoring in Breast Cancer.ACS omega · 2026Article
- RNase L Regulates Antiviral Responsiveness through Cleavage of XBP1 mRNA.bioRxiv : the preprint server for biology · 2026Article
- Refined Design and Liquid-Phase Assembly of GalNAc-siRNA Conjugates: Comparative Efficiency Validation in PCSK9 Targeting.Molecules (Basel, Switzerland) · 2026Article
- Screening Various Bacterial-Produced Double-Stranded RNAs for Managing Asian Soybean Rust Disease Caused byPlants (Basel, Switzerland) · 2026Article
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- Mpox virus OPG175 negatively regulates viral replication by controlling Wnt signaling.iScience · 2025Article
- Rational design of promoter editing confers multipathogen resistance in rice.Genome biology · 2025Article
- Experimental validation of RNA interference technologies for improved control of barber's pole worm.Veterinary research · 2025Article
- Molecular dynamics simulations based siRNA design against GPR10 reveals stable RNAi therapeutics for hormone-dependent uterine fibroids.Scientific reports · 2025Article
- RNase L produces tRNA-derived RNAs that contribute to translation inhibition.RNA (New York, N.Y.) · 2025Article
- Small interfering RNA: From designing to therapeutic in cancer.Journal, genetic engineering & biotechnology · 2025Review
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- Optimizing dsRNA sequences for RNAi in pest control and research with the dsRIP web platform.BMC biology · 2025Article
- Type I Iodothyronine Deiodinase Functions in Thyroid Hormone Synthesis and Growth Regulation in Bivalve.Marine biotechnology (New York, N.Y.) · 2025Article
- The microcephaly-associated transcriptional regulator AUTS2 cooperates with Polycomb complex PRC2 to produce upper-layer neurons in mice.The EMBO journal · 2025Article
57 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRNA interference (RNAi), mediated by 21-nucleotide (nt)-length small interfering RNAs (siRNAs), is a powerful tool not only for studying gene function but also for therapeutic applications. RNAi, requiring perfect complementarity between the siRNA guide strand and the target mRNA, was believed to be extremely specific. However, a recent growing body of evidence has suggested that siRNA could down-regulate unintended genes whose transcripts possess complementarity to the 7-nt siRNA seed region. This off-target gene silencing may often provide incongruous results obtained from knockdown experiments, leading to misinterpretation. Thus, an efficient algorithm for designing functional siRNAs with minimal off-target effect based on the mechanistic features is considered of value.
resultsWe present siDirect 2.0, an update of our web-based software siDirect, which provides functional and off-target minimized siRNA design for mammalian RNAi. The previous version of our software designed functional siRNAs by considering the relationship between siRNA sequence and RNAi activity, and provided them along with the enumeration of potential off-target gene candidates by using a fast and sensitive homology search algorithm. In the new version, the siRNA design algorithm is extensively updated to eliminate off-target effects by reflecting our recent finding that the capability of siRNA to induce off-target effect is highly correlated to the thermodynamic stability, or the melting temperature (Tm), of the seed-target duplex, which is formed between the nucleotides positioned at 2-8 from the 5' end of the siRNA guide strand and its target mRNA. Selection of siRNAs with lower seed-target duplex stabilities (benchmark Tm < 21.5 degrees C) followed by the elimination of unrelated transcripts with nearly perfect match should minimize the off-target effects.
conclusionsiDirect 2.0 provides functional, target-specific siRNA design with the updated algorithm which significantly reduces off-target silencing. When the candidate functional siRNAs could form seed-target duplexes with Tm values below 21.5 degrees C, and their 19-nt regions spanning positions 2-20 of both strands have at least two mismatches to any other non-targeted transcripts, siDirect 2.0 can design at least one qualified siRNA for >94% of human mRNA sequences in RefSeq. siDirect 2.0 is available at http://siDirect2.RNAi.jp/.
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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.