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

Abstract

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.

Keywords

Affiliated Institutions

• Shanghai Institutes for Biological Sciences CN
• University of Chinese Academy of Sciences CN
• Chinese Academy of Sciences CN
• Center for Excellence in Molecular Cell Science CN
• ShanghaiTech University CN
• Center for Excellence in Brain Science and Intelligence Technology CN

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