Off-targeting and other non-specific effects of RNAi experiments in mammalian cells

The RNA interference (RNAi) approach is an efficient and widely used method for silencing plant and animal genes. However, numerous studies have highlighted several obstacles that need to be overcome in order to achieve a specific and efficient silencing effect. Among the major problems of using RNAi in mammalian systems are non-specific effects, such as an undesirable activation of the IFN response, and off-target effects, whereby partial complementarity of an RNAi trigger to non-targeted transcripts causes unwanted silencing effects. The causes of non-specific effects and possible approaches to minimize them are discussed in this review.