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Adenine base editing in mouse embryos and an adult mouse model of Duchenne muscular dystrophy

Cited 137 time in Web of Science Cited 152 time in Scopus
Authors
Ryu, Seuk-Min; Koo, Taeyoung; Kim, Kyoungmi; Lim, Kayeong; Baek, Gayoung; Kim, Sang-Tae; Kim, Heon Seok; Kim, Da-eun; Lee, Hyunji; Chung, Eugene; Kim, Jin-Soo
Issue Date
2018-06
Citation
Nature Biotechnology, Vol.36 No.6, pp.536-539
Abstract
Adenine base editors (ABEs) composed of an engineered adenine deaminase and the Streptococcus pyogenes Cas9 nickase enable adenine-to-guanine (A-to-G) single-nucleotide substitutions in a guide RNA (gRNA)-dependent manner. Here we demonstrate application of this technology in mouse embryos and adult mice. We also show that long gRNAs enable adenine editing at positions one or two bases upstream of the window that is accessible with standard single guide RNAs (sgRNAs). We introduced the Himalayan point mutation in the Tyr gene by microinjecting ABE mRNA and an extended gRNA into mouse embryos, obtaining Tyr mutant mice with an albino phenotype. Furthermore, we delivered the split ABE gene, using trans-splicing adenoassociated viral vectors, to muscle cells in a mouse model of Duchenne muscular dystrophy to correct a nonsense mutation in the Dmd gene, demonstrating the therapeutic potential of base editing in adult animals.
ISSN
1087-0156
URI
https://hdl.handle.net/10371/165702
DOI
https://doi.org/10.1038/nbt.4148
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