Song, C.Q., Jiang, T., Richter, M., Rhym, L.H., Koblan, L.W., Zafra, M.P., Schatoff, E.M., Doman, J.L., Cao, Y., Dow, L.E., Zhu, L.J., Anderson, D.G., Liu, D.R.*, Hao, Y.*, Xue, W.* (2020). Adenine base editing in an adult mouse model of tyrosinaemia. Nature Biomedical Engineering 4, 125-130.

Abstract

Unlike traditional CRISPR-Cas9 homology-directed repair, base editing can correct point mutations without supplying a DNA-repair template. Here, we show in a mouse model of tyrosinemia that hydrodynamic tail-vein injection of plasmid DNA encoding the adenine base editor (ABE) and a single guide RNA can correct an A>G splice-site mutation. ABE treatment partially restored splicing, generated fumarylacetoacetate hydrolase (Fah)-positive hepatocytes in the liver, and rescued weight loss in the animals. We also generated Fah+ hepatocytes in the liver via lipid-nanoparticle-mediated delivery of chemically modified sgRNA and an mRNA of a codon-optimized base editor that displayed higher base-editing efficiency than the standard ABE. Our findings suggest that adenosine base editing can be used for the correction of genetic disease in adult animals.

原文链接见：

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986236/