Development of a microRNA delivery system based on bacteriophage MS2 virus‐like particles

Recently, microRNA (miRNA)‐mediated RNA interference has been developed as a useful tool in gene function analysis and gene therapy. A major obstacle in miRNA‐mediated RNAi is cellular delivery, which requires an efficient and flexible delivery system. The self‐assembly of the MS2 bacteriophage capsids has been used to develop virus‐like particles (VLPs) for RNA and drug delivery. However, MS2 VLP‐mediated miRNA delivery has not yet been reported. We therefore used an Escherichia coli expression system to produce the pre‐miR 146a contained MS2 VLPs, and then conjugated these particles with HIV‐1 Tat 47–57 peptide. The conjugated MS2 VLPs effectively transferred the packaged pre‐miR146a RNA into various cells and tissues, with 0.92–14.76‐fold higher expression of miR‐146a in vitro and about two‐fold higher expression in vivo , and subsequently suppressed its targeting gene. These findings suggest that MS2 VLPs can be used as a novel vehicle in miRNA delivery systems, and may have applications in gene therapy.