Exploiting microRNA regulation for genetic engineering.

RNA interference (RNAi) has been a landmark discovery in science. A typical application is to knock down the expression of endogenous genes by delivering small interfering RNA (siRNA) into cells triggering the degradation of complementary mRNA. However, RNAi can also be exploited the other way round: making use of the huge diversity of endogenous microRNAs (miRNA), the expression of exogenously introduced genes tagged with artificial miRNA target sequences can be negatively regulated according to the activity of a given miRNA which can be tissue-, lineage-, activation- or differentiation stage specific. This has significantly expanded the regulatory potential of gene transfer vectors and will benefit both basic science and therapeutic applications. This review briefly introduces the reader to the technical basis for exploiting miRNA regulation, followed by a discussion of specific applications for miRNA-regulated vectors/viruses in basic research, gene- and virotherapy.