Normothermic ex vivo liver perfusion (NEVLP) offers the potential to optimize 
graft function prior to liver transplantation (LT). Hepatitis C virus (HCV) is 
dependent on the presence of miRNA(microRNA)-122. Miravirsen, a locked-nucleic 
acid oligonucleotide, sequesters miR-122 and inhibits HCV replication. The aim 
of this study was to assess the efficacy of delivering miravirsen during NEVLP 
to inhibit miR-122 function in a pig LT model. Pig livers were treated with 
miravirsen during NEVLP or cold storage (CS). Miravirsen absorption, miR-122 
sequestration, and miR-122 target gene derepression were determined before and 
after LT. The effect of miravirsen treatment on HCV infection of hepatoma cells 
was also assessed. NEVLP improved miravirsen uptake versus CS. Significant 
miR-122 sequestration and miR-122 target gene derepression were seen with NEVLP 
but not with CS. In vitro data confirmed miravirsen suppression of HCV 
replication after established infection and prevented HCV infection with 
pretreatment of cells, analogous to the pretreatment of grafts in the transplant 
setting. In conclusion, miravirsen delivery during NEVLP is a potential strategy 
to prevent HCV reinfection after LT. This is the first large-animal study to 
provide "proof of concept" for using NEVLP to modify and optimize liver grafts 
for transplantation.