ArticleNucleic acids research2009
Profiling of mismatch discrimination in RNAi enabled rational design of allele-specific siRNAs.
Article in Nucleic acids research, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed.
- Comparative genomics identifies small interfering RNA with activity against all five human betacoronaviruses.Genome medicine · 2026Article
- Silencing HPV: the rise of RNA therapeutics in cervical cancer.Infectious agents and cancer · 2026Review
- Viral sequence analysis of chronic hepatitis B patients treated with the siRNA JNJ-73763989 in phase II clinical trials.JHEP reports : innovation in hepatology · 2025Article
- Learning from fungicide resistance: Evolutionary insights to guide RNAi-based control of fungal crop pathogens.Fungal biology reviews · 2025Article
- Targeted allele-specificMolecular therapy. Nucleic acids · 2025Article
- Allele-specific silencing by RNAi of R92Q and R173W mutations in cardiac troponin T.Experimental biology and medicine (Maywood, N.J.) · 2022Article
- RNA and Protein Determinants Mediate Differential Binding of miRNAs by a Viral Suppressor of RNA Silencing Thus Modulating Antiviral Immune Responses in Plants.International journal of molecular sciences · 2022Article
- Genome wide screen of RNAi molecules against SARS-CoV-2 creates a broadly potent prophylaxis.bioRxiv : the preprint server for biology · 2022Article
- A siRNA targets and inhibits a broad range of SARS-CoV-2 infections including Delta variant.EMBO molecular medicine · 2022Article
- shRNAs Targeting a CommonInternational journal of molecular sciences · 2022Article
- RNAi-Based Biocontrol Products: Market Status, Regulatory Aspects, and Risk Assessment.Frontiers in insect science · 2021Article
- siRNA Design and GalNAc-Empowered Hepatic Targeted Delivery.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Specificity profiling of CRISPR system reveals greatly enhanced off-target gene editing.Scientific reports · 2020Article
- Allele-specific genome targeting in the development of precision medicine.Theranostics · 2020Review
- Management of Pest Insects and Plant Diseases by Non-Transformative RNAi.Frontiers in plant science · 2019Review
- ASPsiRNA: A Resource of ASP-siRNAs Having Therapeutic Potential for Human Genetic Disorders and Algorithm for Prediction of Their Inhibitory Efficacy.G3 (Bethesda, Md.) · 2017Article
- Effective Small Interfering RNA Therapy to Treat CLCN7-dependent Autosomal Dominant Osteopetrosis Type 2.Molecular therapy. Nucleic acids · 2015Article
- siRNAs with decreased off-target effect facilitate the identification of essential genes in cancer cells.Oncotarget · 2015Article
- Article
- A novel measurement of allele discrimination for assessment of allele-specific silencing by RNA interference.Molecular biology reports · 2014Article
Corrections and comments
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Authors and funding
13 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Silencing specificity is a critical issue in the therapeutic applications of siRNA, particularly in the treatment of single nucleotide polymorphism (SNP) diseases where discrimination against single nucleotide variation is demanded. However, no generally applicable guidelines are available for the design of such allele-specific siRNAs. In this paper, the issue was approached by using a reporter-based assay. With a panel of 20 siRNAs and 240 variously mismatched target reporters, we first demonstrated that the mismatches were discriminated in a position-dependent order, which was however independent of their sequence contexts using position 4th, 12th and 17th as examples. A general model was further built for mismatch discrimination at all positions using 230 additional reporter constructs specifically designed to contain mismatches distributed evenly along the target regions of different siRNAs. This model was successfully employed to design allele-specific siRNAs targeting disease-causing mutations of PIK3CA gene at two SNP sites. Furthermore, conformational distortion of siRNA-target duplex was observed to correlate with the compromise of gene silencing. In summary, these findings could dramatically simplify the design of allele-specific siRNAs and might also provide guide to increase the specificity of therapeutic siRNAs.
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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.