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MicroRNAs (miRNAs) are small non-coding RNAs that are important in the pathogenesis of multiple diseases and, therefore, may represent a novel class of targets for therapeutic intervention. However, like the majority of oligonucleotide-based strategies, there are obstacles to their clinical application, including poor cellular uptake due to the low permeability of the cell membrane to negatively charged molecules. MPG is a 27-residue peptide vector which contains a hydrophobic domain derived from the fusion sequence of HIV-1 gp41 and a hydrophilic domain derived from the nuclear localization sequence of SV40 T-antigen. MPG is one of the most promising tools for the non-invasive cellular import of oligonucleotides and analogs. In the present study, a non-covalent peptide-based strategy was used for the efficient delivery of the miRNA-122 (miR-122) mimic and inhibitor into mouse liver cell lines, mouse primary hepatocytes and C. elegans, without any associated cytotoxicity. Moreover, high-performance liquid chromatography analysis determined that MPG and MPGΔNLS delivered the miR-122 mimic and inhibitor into mouse liver cells and effectively regulated cholesterol levels. The results demonstrated that MPG family members may be used for the efficient delivery of miR-122 to regulate cholesterol metabolism, and that this cell-penetrating peptide-based technology may be beneficial for further biological applications of RNA therapeutics in vivo.

Efficient delivery of miR-122 to regulate cholesterol metabolism using a non-covalent peptide-based strategy