What kind of off-target effects do you see from shRNA use?
There is a concern that inducing RNAi using shRNA can give unexpected non-specific effects the at mRNA and protein levels, such as off-target mRNA degradation and protein regulation, and induction of the interferon response. However, by optimizing transduction efficiency using lentiviruses and applying proper controls for the experiment, this will allow you to monitor the presence of non-specific effects.