Schematic overview of the mechanism of RNA silencing in the host cell that leads to transcriptional silencing after retroviral delivery of sh/miRNA. Retroviruses (or vectors) deliver therapeutic shRNA-expressing transgenes that integrate into the genome of the host cell and lead to stable shRNA expression. Expressed shRNAs require the activity of endogenous Exportin 5 for nuclear export . Several proteins are recruited and form a dimer with Dicer which receives and subsequently cleaves the dsRNA generating duplex siRNAs with 2 nt 3' overhangs. These siRNAs activate the RNA-induced silencing complex (RISC) which unwinds the RNA and recruits only the guiding strand to target mRNA which is subsequently cleaved and degraded. The figure is schematic, and the Dicer and RISC complexes can vary dependent on cellular process.