Optimising the delivery of antagomiRs to the neonatal mouse lung

MicroRNA are regulators of organogenesis. To study microRNA in late lung development, microRNA are inhibited in a sequence-specific fashion with antagomiRs, stable small-molecule inhibitors of microRNA function. A drawback of antagomiR administration in newborn mice is the repeated parenteral administration causes trauma and inflammation, as well as difficulty in dosing due to the small injection volumes. We assessed the stability and distribution of an antagomiR applied to pregnant mice, either via the intraperitoneal route, or the intravenous (tail-vein) route, in newborn mice over the early post-natal period. Our data indicate that intraperitoneal and intravenous administration of antagomiRs to pregnant mice resulted in a different time course of organ distribution. After both intraperitoneal and intravenous administration to pregnant mice [at embryonic stage (E)17], no impact of antagomiR-29a-3p on miR-29a-3p expression levels was observed in the lung, liver, heart, kidney, and brain of the pregnant mothers on the day of pup delivery [post-natal (P)1)]. In nursing dams treated with intravenous antagomiR-29a-3p on E17, expression levels of miR-29a-3p were reduced in all organs at P7, while intraperitoneal administration impacted all organs except the lung. By day P14, miR-29a-3p expression levels were reduced in all organs of nursing dams. Only the intraperitoneal route yielded a downregulation of target microRNA expression in pups at P1, while only the intravenous route yielded a downregulation of target microRNA expression in pups at P7. By P14, irrespective of the route of administration, no impact on lung target microRNA levels were noted. These data validate transplacental delivery of antagomiRs in mice.