siRNA Efficiency: Structure or Sequence—That Is the Question

The triumphant success of RNA interference (RNAi) in life sciencesis based on its high potency to silence genes in asequence-specific manner. Nevertheless, the first task forsuccessful RNAi approaches is the identification of highly activesmall interfering RNAs (siRNAs). Early on, it has been found thatthe potency of siRNAs can varydrastically. Great progress was made when thermodynamic properties that influence siRNA activity were discovered. Designalgorithms based on these parameters enhance the chance togenerate potent siRNAs. Still, many siRNAs designed accordinglyfail to silence their targeted gene, whereas others are highlyefficient despite the fact that they do not fulfil the recommendedcriteria. Therefore, the accessibility of the siRNA-binding siteon the target RNA has been investigated as an additional parameterwhich is important for RNAi-mediated silencing. These and otherfactors which are crucial for successful RNAi approaches will bediscussed in the present review