| First Author | Lee HK | Year | 2020 |
| Journal | Commun Biol | Volume | 3 |
| Issue | 1 | Pages | 19 |
| PubMed ID | 31925293 | Mgi Jnum | J:288960 |
| Mgi Id | MGI:6433624 | Doi | 10.1038/s42003-019-0745-3 |
| Citation | Lee HK, et al. (2020) Cytosine base editor 4 but not adenine base editor generates off-target mutations in mouse embryos. Commun Biol 3(1):19 |
| abstractText | 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. |
