MicroRNA-regulated viral vectors for gene therapy

Figure 2 Adeno-associated virus vector-based microRNA targeting strategies to improve cardiac - specific gene therapy. Cardiac-specific gene transfer of AAV vectors can be obtained by different targeting strategies, including transcriptional targeting using cardiac hybrid promoters[68,122], transductional targeting[109-113,187,188] or microRNA-regulated post-transcriptional transgene suppression. miR-OFF system (right site): Expression of miR-TS-bearing transgenes can be selectively suppressed in non-cardiac tissue by microRNAs, which are expressed in these tissues, but not in the heart. For the miR-OFF system (left site): If microRNAs are selectively down-regulated in cardiovascular diseases, transgene expression may be restricted to these cells by use of miR-TS corresponding to down-regulated microRNAs. If microRNAs are up-regulated in cardiovascular diseases, corresponding miR-TS can be used in the miR-ON system[178] for regulation of a repressor protein to restrict transgene expression to respective cells. Shown microRNAs are specifically expressed in mouse tissues (unpublished). AAV: Adeno-associated virus; pA: Polyadenylation site; CMV: Cytomegalovirus; MLC: Myosin light chain; MHC: Myosin heavy chain; TNT: Troponin T.