High Mutation Rates in Non-human Primates Edited by Cytosine Base Editors

Gene-edited animals are being produced and used in ever-increasing numbers. However, their genome-wide mutation rates remain largely unknown. To characterize the mutation rates in animals edited by different gene editors, we analysed the publicly available genome sequencing datasets of parent-offspring trios. Unexpectedly, we found that the mutation rate in non-human primates edited by cytosine base editors (CBEs) was extremely high, approximately 158-fold higher than the unedited controls, while the mutation rate in CBE-edited mice was about 4-fold higher than unedited mice. Our results highlight the necessity to evaluate whole-genome de novo mutations using a streamlined analysis pipeline when CBEs are used to manipulate target genes in animals, especially when they are used for translational medicine.