Breakfast Workshop
08:00-08:45, 18 September 2008
Chemical Modifications in the Seed Region Backbone can Significantly Reduce siRNA Off-Target Effects
Presented by Erik Eastlund, Senior Scientist, Sigma Life Science
Booth # 29
RNA interference has revolutionized reverse genetics for mammalian cells by providing rapid and simple methods for reducing gene expression. In recent years since the wide adoption of synthetic siRNA, it has become well established that the seed region in the antisense strand is responsible for creating off-target effects, primarily mediated through interactions with seed region compliments in the 3'-UTR of off-target mRNAs. The small size of the seed region (6-8 bp) has prevented a genome-wide bioinformatic solution to this problem. Additionally, while several chemical modifications have been reported to affect off-target activity, it is still unclear how chemical modifications increase siRNA specificity and to what maximal extent various chemical modifications can reduce off-target effects. We have discovered that a novel chemical modification placed in the backbone of the seed region of the antisense strand can significantly reduce off-target effects in gene silencing experiments and will present DNA microarray data quantifying the increased specificity for several different gene targets.