Effect of the guide strand 3{'}-end structure on the gene silencing potency of asymmetric siRNA

In this study, we explored the effect of the guide strand 3’-end structure on the gene silencing potency of asiRNA. Interestingly, asiRNAs with a 21 nucleotide (nt) guide strand solely composed of RNA resulted in gene silencing more than 6-fold more efficient compared with the corresponding asiRNA guide strand harboring a deoxythymidine dinucleotide (dTdT) at its 3'-end. We demonstrated that the molecular basis of potency of the asiRNA with a 21 nt guide strand composed solely of RNA was due to the enhanced formation of the RNA- induced silencing complex (RISC) and increased affinity towards human Argonaute2 (hAgo2). Our observations may assist researchers in designing new asiRNAs with high on-target silencing efficiency with low off-target effects, which is critical for applications in both basic research and therapeutic development.

Source: BJ Gene - May 6, 2014 Category: Biochemistry Authors: S Hong, J Park, S Yun, C Lee, C Shin, D Lee Tags: BJ Biomolecules Source Type: research