RNA interference (RNAi) was discovered as a cellular defense mechanism more than decade ago. It has been exploited as a powerful tool for genetic manipulation. Characterized with specifically silencing target gene expression, it has great potential application for disease treatment. Currently, there are human clinical trials in progress or planned. Despite the excitement regarding this prominent technology, there are many obstacles and concerns that prevent RNAi from being widely used in the therapeutic field. Among them, the non-spatial and non-temporal control is the most difficult challenge, as well as off-target effects and triggering type I immune responses. Inducible RNAi technology can effectively regulate target genes by inducer-mediated small hairpin RNA expression. Combination with inducible regulation systems this makes RNAi technology more sophisticated and may provide a wider application field. This review discusses approaches of inducible RNAi systems, the potential problem areas and solutions and their therapeutic applications. Given the limitations discussed herein being resolved, we believe that inducible RNAi will be a major therapeutic modality within the next several years.
Keywords: Applications; RNAi; inducible RNAi systems; lncRNAs; shRNA; therapeutics.