A screen of chemical modifications identifies position-specific modification by UNA to most potently reduce siRNA off-target effects.

ABSTRACT: Small interfering RNAs (siRNAs) are now established as the preferred tool to inhibit gene function in mammalian cells yet trigger unintended gene silencing due to their inherent miRNA-like behavior. Such off-target effects are primarily mediated by the sequence-specific interaction between the siRNA seed regions (position 2-8 of either siRNA strand counting from the 5'-end) and complementary sequences in the 3'UTR of (off-) targets. It was previously shown that chemical modification of siRNAs can reduce off-targeting but only very few modifications have been tested leaving more to be identified. Here we developed a luciferase reporter-based assay suitable to monitor siRNA off-targeting in a high throughput manner using stable cell lines. We investigated the impact of chemically modifying s

SUBMITTER: Bramsen JB 

PROVIDER: S-EPMC2943616 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature