Hereditary tyrosinaemia type I (HT-I) is a lethal liver disease that is caused by mutations in FAH, which encodes fumarylacetoacetate hydrolase, the enzyme that catalyses the final step of tyrosine catabolism. FAH deficiency leads to the accumulation of toxic metabolic intermediates that cause hepatocellular carcinoma. Pankowicz et al. tested the efficacy of reprogramming tyrosine metabolism by gene disruption, which should be more feasible than FAH gene correction. They injected the CRISPR–Cas components to the tail vein of HT-I (Fah−/−) mice and inactivated Hpd, the gene encoding hydroxyphenylpyruvate dioxygenase, which functions upstream of FAH. Edited (Fah−/−/Hpd−/−) hepatocytes had a growth advantage over non-edited (Fah−/−) hepatocytes and they replaced the entire liver in a few weeks. Fah−/−/Hpd−/− mice had significantly reduced levels of toxic metabolic intermediates and were cured of HT-I.