Multiplex precise base editing in cynomolgus monkeys

Wenhui Zhang, Tomomi Aida (), Ricardo C. H. Rosario, Jonathan J. Wilde, Chenhui Ding, Xiaohui Zhang, Zulqurain Baloch, Yan Huang, Yu Tang, Duanduan Li, Hongyu Lu, Yang Zhou, Minqing Jiang, Dongdong Xu, Zhihao Fang, Zhanhong Zheng, Qunshan Huang, Guoping Feng () and Shihua Yang ()
Additional contact information
Wenhui Zhang: South China Agricultural University
Tomomi Aida: Massachusetts Institute of Technology
Ricardo C. H. Rosario: Broad Institute of MIT and Harvard
Jonathan J. Wilde: Massachusetts Institute of Technology
Chenhui Ding: Reproductive Medicine Center, the First Affiliated Hospital of Sun Yat-sen University
Xiaohui Zhang: East China Normal University
Zulqurain Baloch: South China Agricultural University
Yan Huang: South China Agricultural University
Yu Tang: South China Agricultural University
Duanduan Li: South China Agricultural University
Hongyu Lu: South China Agricultural University
Yang Zhou: Massachusetts Institute of Technology
Minqing Jiang: Massachusetts Institute of Technology
Dongdong Xu: South China Agricultural University
Zhihao Fang: South China Agricultural University
Zhanhong Zheng: South China Agricultural University
Qunshan Huang: South China Agricultural University
Guoping Feng: Massachusetts Institute of Technology
Shihua Yang: South China Agricultural University

Nature Communications, 2020, vol. 11, issue 1, 1-12

Abstract: Abstract Common polygenic diseases result from compounded risk contributed by multiple genetic variants, meaning that simultaneous correction or introduction of single nucleotide variants is required for disease modeling and gene therapy. Here, we show precise, efficient, and simultaneous multiplex base editing of up to three target sites across 11 genes/loci in cynomolgus monkey embryos using CRISPR-based cytidine- and adenine-base editors. Unbiased whole genome sequencing demonstrates high specificity of base editing in monkey embryos. Our data demonstrate feasibility of multiplex base editing for polygenic disease modeling in primate zygotes.

Date: 2020
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DOI: 10.1038/s41467-020-16173-0

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