Journal
COMMUNICATIONS BIOLOGY
Volume 3, Issue 1, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s42003-019-0745-3
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Funding
- Intramural Research Programs (IRPs) of National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- National Heart, Lung, and Blood Institute (NHLBI)
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [ZICHL005907] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [ZIADK061000, ZICDK071001] Funding Source: NIH RePORTER
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Hye Kyung Lee, Harold E. Smith et al. examined the fidelity of cytosine base editor 4 (BE4) and adenine base editors (ABEs) in mouse embryos using whole-genome sequencing of a family-based trio cohort. They show that BE4-edited mice carry more single-nucleotide variants and deletions than ABE-edited mice. Deaminase base editing has emerged as a tool to install or correct point mutations in the genomes of living cells in a wide range of organisms. However, the genome-wide off-target effects introduced by base editors in the mammalian genome have been examined in only one study. Here, we have investigated the fidelity of cytosine base editor 4 (BE4) and adenine base editors (ABE) in mouse embryos using unbiased whole-genome sequencing of a family-based trio cohort. The same sgRNA was used for BE4 and ABE. We demonstrate that BE4-edited mice carry an excess of single-nucleotide variants and deletions compared to ABE-edited mice and controls. Therefore, an optimization of cytosine base editors is required to improve its fidelity. While the remarkable fidelity of ABE has implications for a wide range of applications, the occurrence of rare aberrant C-to-T conversions at specific target sites needs to be addressed.
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