siRNA Design Software for a Target Gene-Specific RNA Interference
Open Access
- 1 January 2012
- journal article
- review article
- Published by Frontiers Media SA in Frontiers in Genetics
- Vol. 3, 102
- https://doi.org/10.3389/fgene.2012.00102
Abstract
RNA interference (RNAi) is the mechanism through which small interfering RNA (siRNA) induces sequence-specific posttranscriptional gene silencing. RNAi is commonly recognized as a powerful tool not only for functional genomics but also for therapeutic applications. Twenty one-nucleotide-long siRNA suppresses the expression of the intended gene whose transcript possesses perfect complementarity to the siRNA guide strand. Hence, its silencing effect has been assumed to be extremely specific. However, accumulated evidences revealed that siRNA could downregulate unintended genes with partial complementarities mainly to the 7-nucleotide seed region of siRNA. This phenomenon is referred to as off-target effect. We have revealed that the capability to induce off-target effect is strongly correlated to the thermodynamic stability in siRNA seed-target duplex. For understanding accurate target gene function and successful therapeutic application, it may be critical to select a target gene-specific siRNA with minimized off-target effect. Here we present our siRNA design software for a target-specific RNAi. In addition, we also introduce the softwares open to the public for designing functional siRNAs.Keywords
This publication has 37 references indexed in Scilit:
- Structural basis for 5′-nucleotide base-specific recognition of guide RNA by human AGO2Nature, 2010
- siDirect 2.0: updated software for designing functional siRNA with reduced seed-dependent off-target effectBMC Bioinformatics, 2009
- sIR: siRNA Information Resource, a web-based tool for siRNA sequence design and analysis and an open access siRNA databaseBMC Bioinformatics, 2007
- Widespread siRNA “off-target” transcript silencing mediated by seed region sequence complementarityRNA, 2006
- Cleavage of the siRNA passenger strand during RISC assembly in human cellsEMBO Reports, 2006
- Argonaute2 Cleaves the Anti-Guide Strand of siRNA during RISC ActivationCell, 2005
- Crystal Structure of A. aeolicus Argonaute, a Site-Specific DNA-Guided Endoribonuclease, Provides Insights into RISC-Mediated mRNA CleavageMolecular Cell, 2005
- Sfold web server for statistical folding and rational design of nucleic acidsNucleic Acids Research, 2004
- An algorithm for selection of functional siRNA sequencesBiochemical and Biophysical Research Communications, 2004
- Analysis of gene function in somatic mammalian cells using small interfering RNAsMethods, 2002