shRNA (short hairpin RNA)

shRNA can be used for global identification of genes involved in certain functional pathways by blocking their expression (Moffat J et al 2006 Cell 124:1283). By intravenous infusion of 49 Adeno-associated virus vectors carrying different shRNAs, 36 caused dose-dependent liver injuries and 23 caused death in adult mice. Liver-derived microRNA pathway was down-regulated by nuclear karyopherin/exportin-5. (Grimm D et al 2006 Nature [Lond] 441:537). Reversible gene inactivation was attained by expression of an insulin receptor (Insr)-specific shRNA. Upon induction by doxycycline, mice developed severe hyperglycemia within seven days. The onset and progression of the disease correlates with the concentration of doxycycline, and the phenotype returns to the baseline, shortly after the withdrawal of the inductor doxycycline (Seibler J et al 2007 Nucleic Acids Res 35(7):e54). RNAi, microrna, karyopherin; Paddison PJ 2002 Genes Dev 8:948.