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


ABSTRACT: 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.

SUBMITTER: Tao W 

PROVIDER: S-EPMC8413891 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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

Tao Wanyu W   Liu Qing Q   Huang Shisheng S   Wang Xin X   Qu Shiyuan S   Guo Junfan J   Ou Danfeng D   Li Guanglei G   Zhang Yu Y   Xu Xiangmin X   Huang Xingxu X  

Molecular therapy. Nucleic acids 20210729


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  ...[more]

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