CABE-RY: A PAM-flexible dual-mutation base editor for reliable modeling of multi-nucleotide variants

• Main Authors: Wanyu Tao (Author), Qing Liu (Author), Shisheng Huang (Author), Xin Wang (Author), Shiyuan Qu (Author), Junfan Guo (Author), Danfeng Ou (Author), Guanglei Li (Author), Yu Zhang (Author), Xiangmin Xu (Author), Xingxu Huang (Author)
• Format: Book
• Published: Elsevier, 2021-12-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Multi-nucleotide variants (MNVs) represent an important type of genetic variation and have biological and clinical significance. To simulate MNVs, we designed four dual-mutation base editors combining hA3A(Y130F), TadA8e(V106W), and protospacer adjacent motif (PAM)-flexible SpRY and selected cytosine and adenine base editor-SpRY (CABE-RY), which had the best editing performance, for further study. Characterization and comparison showed that CABE-RY had a smaller DNA editing window and lower RNA off-target edits than the corresponding single base editors. Thus, we have established a versatile tool to efficiently simulate MNVs over the genome, which could be very useful for functional studies on MNVs in humans.

Item Description

2162-2531
10.1016/j.omtn.2021.07.016