Monogenic diseases are caused by a mutation in a single gene, which can have severe implications for the development and health of patients over their lifetime. One such disease is the metabolic liver disorder phenylketonuria (PKU), which can cause neurological deficits in infants when left untreated. Could such serious diseases be treated or even cured on the genetic level?  

Desirée Böck, Tanja Rothgangl and Lukas Villiger used a novel gene editing technology, called «prime editing», which has the potential to directly repair disease-causing mutations in monogenic diseases, such as PKU. The scientists optimized and applied prime editing to cure PKU in a respective mouse model. They first reduced the size of the prime editor (a fusion protein of Cas9 and a reverse transcriptase) in order to facilitate in vivo delivery to newborn and adult animals in a second step. The observed editing rates were dose-dependent and sufficient to cure the disease in animals permanently. 

The three awardees could show that the prime editing technology is functional and highly precise in the mouse liver. In conclusion, this study demonstrates the potential of this novel tool in vivo. Further studies are required to examine if this technology could be used in the future to help patients suffering from various monogenic diseases.

In vivo prime editing of a metabolic liver disease in mice. Desirée Böck, Tanja Rothgangl, Lukas Villiger, Lukas Schmidheini, Mai Matsushita, Nicolas Mathis, Eleonora Ioannidi, Nicole Rimann, Hiu Man Grisch-Chan, Susanne Kreutzer, Zacharias Kontarakis, Manfred Kopf, Beat Thöny, Gerald Schwank. Sci Transl Med. 2022 Mar 16;14(636):eabl9238.