Ongoing liver-directed gene therapy clinical trials are focused on Pompe disease, Urea cycle disorders such as ornithine transcarbamylase (OTC) deficiency, methylmalonic acidemia (MMA), and Wilson disease, among others, while first AAV gene therapies for hemophilia A and B have already been approved for use in patients1,2. Here, OTC is linked to ornithine carbamoyltransferase deficiency.