» Articles » PMID: 32393762

Multiplex Precise Base Editing in Cynomolgus Monkeys

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.

Citing Articles

Pancreatic agenesis and altered m6A methylation in the pancreas of PDX1-mutant cynomolgus macaques.

Zhang W, Zhuang J, Guo Y, Chen X, Li Y, Xu J Zool Res. 2024; 45(6):1188-1200.

PMID: 39318126 PMC: 11668947. DOI: 10.24272/j.issn.2095-8137.2024.044.


Genome editing: An insight into disease resistance, production efficiency, and biomedical applications in livestock.

Yuan Y, Liu S, Farhab M, Lv M, Zhang T, Cao S Funct Integr Genomics. 2024; 24(3):81.

PMID: 38709433 DOI: 10.1007/s10142-024-01364-5.


Deconstructing cancer with precision genome editing.

Johnson G, Gould S, Sanchez-Rivera F Biochem Soc Trans. 2024; 52(2):803-819.

PMID: 38629716 PMC: 11088927. DOI: 10.1042/BST20230984.


Embryo and fetal gene editing: Technical challenges and progress toward clinical applications.

Mattar C, Chew W, Lai P Mol Ther Methods Clin Dev. 2024; 32(2):101229.

PMID: 38533521 PMC: 10963250. DOI: 10.1016/j.omtm.2024.101229.


Gene-knockout by iSTOP enables rapid reproductive disease modeling and phenotyping in germ cells of the founder generation.

Wang Y, Chen J, Huang X, Wu B, Dai P, Zhang F Sci China Life Sci. 2024; 67(5):1035-1050.

PMID: 38332217 DOI: 10.1007/s11427-023-2408-2.


References
1.
Kaiser T, Feng G . Modeling psychiatric disorders for developing effective treatments. Nat Med. 2015; 21(9):979-88. PMC: 4886231. DOI: 10.1038/nm.3935. View

2.
Schwank G, Koo B, Sasselli V, Dekkers J, Heo I, Demircan T . Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell. 2013; 13(6):653-8. DOI: 10.1016/j.stem.2013.11.002. View

3.
Gaudelli N, Komor A, Rees H, Packer M, Badran A, Bryson D . Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage. Nature. 2017; 551(7681):464-471. PMC: 5726555. DOI: 10.1038/nature24644. View

4.
Komor A, Kim Y, Packer M, Zuris J, Liu D . Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature. 2016; 533(7603):420-4. PMC: 4873371. DOI: 10.1038/nature17946. View

5.
Nishida K, Arazoe T, Yachie N, Banno S, Kakimoto M, Tabata M . Targeted nucleotide editing using hybrid prokaryotic and vertebrate adaptive immune systems. Science. 2016; 353(6305). DOI: 10.1126/science.aaf8729. View