Are there any toxic effects of shRNA in animal models?
The toxic effect can be due to introduction of off-target effects which could be sequence-dependant when the shRNA sequence has homology to mRNA transcripts other than the gene of interest. Sequence-independent off-target effect can trigger a stress related interferon response. While the induction of interferon-pathway during RNAi is usually attributed to long, double-stranded nucleic acids, it can also be a concern during transduction of shRNA molecules. Stress responses may affect general cellular expression levels and can confuse and mislead the interpretation of data obtained from RNAi experiments.
