Publication: Adenine Base Editing in an Adult Mouse Model of Tyrosinaemia
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Date
2019-02-25
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Springer Science and Business Media LLC
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Song, Chun-Qing, Tingting Jiang, Michelle Richter, Luke H. Rhym, Luke Koblan, Maria Paz Zafra, Emma M. Schatoff et al. "Adenine Base Editing in an Adult Mouse Model of Tyrosinaemia." Nature Biomedical Engineering 4, no. 1 (2019): 125-130. DOI: 10.1038/s41551-019-0357-8
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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.
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Research Subject Categories::TECHNOLOGY::Bioengineering::Genetic engineering including functional genomics
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