How are the Silencer Select siRNAs improved over Silencer siRNAs?
These siRNA sequences are generated with a new algorithm. This algorithm was developed by Ambion’s bioinformatics group using a support vector machine (SVM) approach. The SVM approach takes a classification approach rather than a linear regression approach, and results in the ability to differentiate “hyperfunctional” versus “acceptable” siRNAs. Specificity is enhanced by including bioinformatic filters that remove siRNAs with too few mismatches to unintended targets–those that are potentially toxic, those that match naturally occurring miRNA seed regions and those with antiviral response motifs. Also, siRNAs are ranked by frequency of potential siRNA seed region matches in the 3’UTR of off-target transcripts. Compared to Silencer siRNA Designs, Silencer Select Designs elicit > 80% target mRNA knockdown, 28% more often. Last but not least, Silencer Select siRNAs are modified to enhance specificity. We have shown that the modifications result in reduction of off-target effects by up to
