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Efficient generation of mouse models of human diseases via ABE- and BE-mediated base editing.

ABSTRACT: A recently developed adenine base editor (ABE) efficiently converts A to G and is potentially useful for clinical applications. However, its precision and efficiency in vivo remains to be addressed. Here we achieve A-to-G conversion in vivo at frequencies up to 100% by microinjection of ABE mRNA together with sgRNAs. We then generate mouse models harboring clinically relevant mutations at Ar and Hoxd13, which recapitulates respective clinical defects. Furthermore, we achieve both C-to-T and A-to-G base editing by using a combination of ABE and SaBE3, thus creating mouse model harboring multiple mutations. We also demonstrate the specificity of ABE by deep sequencing and whole-genome sequencing (WGS). Taken together, ABE is highly efficient and precise in vivo, making it feasible to model and potentially cure relevant genetic diseases.

SUBMITTER: Liu Z

PROVIDER: S-EPMC6002399 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Efficient generation of mouse models of human diseases via ABE- and BE-mediated base editing.

Liu Zhen Z Lu Zongyang Z Yang Guang G Huang Shisheng S Li Guanglei G Feng Songjie S Liu Yajing Y Li Jianan J Yu Wenxia W Zhang Yu Y Chen Jia J Sun Qiang Q Huang Xingxu X

Nature communications 20180614 1

A recently developed adenine base editor (ABE) efficiently converts A to G and is potentially useful for clinical applications. However, its precision and efficiency in vivo remains to be addressed. Here we achieve A-to-G conversion in vivo at frequencies up to 100% by microinjection of ABE mRNA together with sgRNAs. We then generate mouse models harboring clinically relevant mutations at Ar and Hoxd13, which recapitulates respective clinical defects. Furthermore, we achieve both C-to-T and A-to ...[more]

PMID: 29904106

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