Efficient generation of pathogenic A-to-G mutations in human tripronuclear embryos via ABE-mediated base editing

Published on Jun 1, 2019in Molecular therapy. Nucleic acids5.92
· DOI :10.1016/j.omtn.2019.05.021
Guanglei Li4
Estimated H-index: 4
(Guangzhou Medical University),
Xinyi Liu (JNU: Jinan University)+ 8 AuthorsJianqiao Liu2
Estimated H-index: 2
(Guangzhou Medical University)
Base editing systems show their power in modeling and correcting the pathogenic mutations of genetic diseases. Previous studies have already demonstrated the editing efficiency of BE3-mediated C-to-T conversion in human embryos. However, the precision and efficiency of a recently developed adenine base editor (ABE), which converts A-to-G editing in human embryos, remain to be addressed. Here we selected reported pathogenic mutations to characterize the ABE in human tripronuclear embryos. We found effective A-to-G editing occurred at the desirable sites using the ABE system. Furthermore, ABE-mediated A-to-G editing in the single blastomere of the edited embryos exhibited high product purity. By deep sequencing and whole-genome sequencing, A or T mutations didn’t increase significantly, and no off-target or insertion or deletion (indel) mutations were detected in these edited embryos, indicating the ABE-mediated base editing in human embryos is precise and controllable. For some sites, since a different editing pattern was obtained from the cells and the embryos targeted with the same single guide RNA (sgRNA), it suggests that ABE-mediated editing might have different specificity in vivo . Taken together, we efficiently generated pathogenic A-to-G mutations in human tripronuclear embryos via ABE-mediated base editing.
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