Authors
Song, Chun-QingJiang, Tingting
Richter, Michelle
Rhym, Luke H.
Koblan, Luke W.
Zafra, Maria Paz
Schatoff, Emma M.
Doman, Jordan L.
Cao, Yueying
Dow, Lukas E.
Zhu, Lihua Julie
Anderson, Daniel G.
Liu, David R.
Yin, Hao
Xue, Wen
UMass Chan Affiliations
Li Weibo Institute for Rare Diseases ResearchProgram in Molecular Medicine
Department of Molecular, Cell and Cancer Biology
RNA Therapeutics Institute
Document Type
Journal ArticlePublication Date
2020-01-01Keywords
base editinggenetic diseases
tyrosinaemia
Bioinformatics
Computational Biology
Congenital, Hereditary, and Neonatal Diseases and Abnormalities
Genetic Phenomena
Molecular, Cellular, and Tissue Engineering
Nucleic Acids, Nucleotides, and Nucleosides
Therapeutics
Metadata
Show full item recordAbstract
In contrast to 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 tyrosinaemia that hydrodynamic tail-vein injection of plasmid DNA encoding the adenine base editor (ABE) and a single-guide RNA (sgRNA) 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 mice. We also generated FAH(+) hepatocytes in the liver via lipid-nanoparticle-mediated delivery of a chemically modified sgRNA and an mRNA of a codon-optimized base editor that displayed higher base-editing efficiency than the standard ABEs. Our findings suggest that adenine base editing can be used for the correction of genetic diseases in adult animals.Source
Song CQ, Jiang T, Richter M, Rhym LH, Koblan LW, Zafra MP, Schatoff EM, Doman JL, Cao Y, Dow LE, Zhu LJ, Anderson DG, Liu DR, Yin H, Xue W. Adenine base editing in an adult mouse model of tyrosinaemia. Nat Biomed Eng. 2020 Jan;4(1):125-130. doi: 10.1038/s41551-019-0357-8. Epub 2019 Feb 25. PMID: 31740768; PMCID: PMC6986236. Link to article on publisher's site
DOI
10.1038/s41551-019-0357-8Permanent Link to this Item
http://hdl.handle.net/20.500.14038/41351PubMed ID
31740768Related Resources
ae974a485f413a2113503eed53cd6c53
10.1038/s41551-019-0357-8