High Performance TadA-8e Derived Cytosine and Dual Base Editors with Undetectable Off-target Effects in Plants

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Jun 14

PMID 38877035

Authors

Tingting Fan

Yanhao Cheng

Yuechao Wu

Shishi Liu

Xu Tang

Yao He

Shanyue Liao

Xuelian Zheng

Tao Zhang

Yiping Qi

Yong Zhang

Affiliations

Soon will be listed here.

Abstract

Cytosine base editors (CBEs) and adenine base editors (ABEs) enable precise C-to-T and A-to-G edits. Recently, ABE8e, derived from TadA-8e, enhances A-to-G edits in mammalian cells and plants. Interestingly, TadA-8e can also be evolved to confer C-to-T editing. This study compares engineered CBEs derived from TadA-8e in rice and tomato cells, identifying TadCBEa, TadCBEd, and TadCBEd_V106W as efficient CBEs with high purity and a narrow editing window. A dual base editor, TadDE, promotes simultaneous C-to-T and A-to-G editing. Multiplexed base editing with TadCBEa and TadDE is demonstrated in transgenic rice, with no off-target effects detected by whole genome and transcriptome sequencing, indicating high specificity. Finally, two crop engineering applications using TadDE are shown: introducing herbicide resistance alleles in OsALS and creating synonymous mutations in OsSPL14 to resist OsMIR156-mediated degradation. Together, this study presents TadA-8e derived CBEs and a dual base editor as valuable additions to the plant editing toolbox.

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