Delivery and biological Activity of Therapeutic miRNAs and miRNA Modifiers

Delivery of microRNAs (miRNAs), therapeutic molecules that mimic miRNA activity, and antagomiRs is a strategy to control and modify gene expression in eukaryotic systems in vitro and in vivo. Therapeutic miRNAs and pre-miRNAs should display stability in biological fluids and efficient cellular uptake. Accordingly, the use of delivery systems based on microspheres, nanospheres, liposomes, and other “transfectant” reagents has been proposed. Exosomes can act as extracellular vehicles by which cells communicate through the delivery of functional molecules, including microRNAs, to recipient cells. This has many important biological, physiological, and pathological implications. Among the molecules studied for miRNA therapeutics, some are designed to mimic miRNA activity (miRNA replacement therapy) or interfere with it (antagomiR therapy). Among antagomiRs, peptide nucleic acids (PNAs) are promising; after suitable modification, they exhibit highly efficient uptake, stability, and biological activity.