Synergistic effects between analogs of DNA and RNA improve the potency of siRNA-mediated gene silencing.

ABSTRACT: We report that combining a DNA analog (2'F-ANA) with rigid RNA analogs [2'F-RNA and/or locked nucleic acid (LNA)] in siRNA duplexes can produce gene silencing agents with enhanced potency. The favored conformations of these two analogs are different, and combining them in a 1-1 pattern led to reduced affinity, whereas alternating short continuous regions of individual modifications increased affinity relative to an RNA:RNA duplex. Thus, the binding affinity at key regions of the siRNA duplex could be tuned by changing the pattern of incorporation of DNA-like and RNA-like nucleotides. These heavily or fully modified duplexes are active against a range of mRNA targets. Effective patterns of modification were chosen based on screens using two sequences targeting firefly luciferase. We then ap

SUBMITTER: Deleavey GF 

PROVIDER: S-EPMC2910058 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature