In vivo adenine base editing in an adult mouse model of tyrosinemia

Base editing, a method for correcting genetic mutations, has broad potential utility. Unlike traditional CRISPR-Cas9 homology directed repair (HDR), point mutations can be corrected without supplying a DNA repair template. Here we show in a mouse model of tyrosinemia that hydrodynamic injection of plasmid DNA encoding adenine base editor (ABE) and a single-guide RNA corrected an A>G splice site mutation. ABE treatment partially restored splicing, generated Fah-positive hepatocytes, and rescued weight loss in vivo.