@misc{10481/110174,
year = {2020},
month = {1},
url = {https://hdl.handle.net/10481/110174},
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.},
organization = {National Institutes of Health ((NIH) DP2HL137167, P01HL131471 and UG3HL147367)},
organization = {American Cancer Society (129056-RSG-16-093)},
organization = {Lung Cancer Research Foundation, Hyundai Hope on Wheels, UMass CCTS and ALS Association},
organization = {DARPA HR0011-17-2-0049; US NIH RM1 HG009490, R01 EB022376, U01 AI142756 and R35 GM118062; HHMI, R01 CA195787; K22 CA181280},
organization = {Marble Center for Cancer Nanomedicine},
organization = {HHMI National Cancer Institute P30-CA14051},
organization = {NIH Training Grant T32 GM095450},
organization = {National Natural Science Foundation of China 31871345},
organization = {Wuhan University},
publisher = {Springer Nature},
keywords = {Base Editing},
keywords = {Animal models},
keywords = {CRISPR-CAS9},
title = {Adenine base editing in an adult mouse model of tyrosinemia},
doi = {10.1038/s41551-019-0357-8},
author = {Song, Chun-Qing and Jiang, Tingting and Richter, Michelle and Rhym, Luke H. and Koblan, Luke W. and Zafra, María Paz and Schatoff, Emma M. and Doman, Jordan L. and Cao, Yueying and Dow, Lukas E. and Zhu, Lihua Julie and Anderson, Daniel G. and Liu, David R. and Yin, Hao and Xue, Wen},
}