The use of microRNA mimics to increase microRNA levels in the developing organs of newborn mice.

MicroRNA are emerging of important regulators of cell and tissue differentiation, organ development, and disease pathogenesis. The use of microRNA antimiRs which deplete microRNA pools is a well-established and successful intervention in both in vivo and in vitro settings, where the goal is to reduce the abundance of selected microRNA species. However, whilst efforts to increase the abundance of selected microRNA species in vitro have found widespread success in cell culture, delivering functional microRNA to the organs of living, intact experimental animals remains problematic. The objective of this study was to examine the efficacy of delivery of commercially-available microRNA mimics that are marketed for in vitro and in vivo use to multiple organs of the laboratory mouse, following parenteral administration in various protocols over the first 14 days of post-natal life. The data presented indicate that parenteral administration of a microRNA mimic is largely inefficient, with moderate delivery of a miR-497a-5p mimic noted in the liver, but not the kidneys, lungs, heart, or brain. Changes in the abundance of a limited number of mRNA and protein targets in the liver were observed, using batch RNA-Seq and proteomic screening; indicting the delivery of a miR-497a-5p mimic had functional consequences for the liver transcriptome and proteome. These data highlight the potential utility of commercially-available microRNA mimics in an in vivo setting, however, these data also highlight notable hurdles that still need to be overcome to facilitate the further use of microRNA mimics to study physiological processes in living, intact organisms.