Research ArticleGene Therapy

Curative ex vivo liver-directed gene therapy in a pig model of hereditary tyrosinemia type 1

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Science Translational Medicine  27 Jul 2016:
Vol. 8, Issue 349, pp. 349ra99
DOI: 10.1126/scitranslmed.aaf3838

Skipping the waiting list

The only cure for hereditary tyrosinemia type 1 (HT1)—an inherited metabolic disease—is a liver transplant. However, owing to the shortage of liver donors, Hickey et al. turned to gene therapy as a way to cure HT1. The authors took liver cells from pigs that have HT (through a defect in the gene Fah), transduced them with the correct Fah, and then put the cells back into the same animals. The ex vivo gene therapy approach prevented liver failure and fibrosis and also restored metabolic function, which is deteriorated in HT1 disease. Having demonstrated in large animals the use of materials that are safe for use in people, the technology is now poised to move into patients, to regenerate their own livers and spare them the long wait times on the liver transplant list.