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Cytosine, but not adenine, base editors induce genome-wide off-target mutations in rice
Abstract
Spotting off-targets from gene editing Unintended genomic modifications limit the potential therapeutic use of gene-editing tools. Available methods to find off-targets generally do not work in vivo or detect single-nucleotide changes. Three papers in this issue report new methods for monitoring gene-editing tools in vivo (see the Perspective by Kempton and Qi). Wienert et al. followed the recruitment of a DNA repair protein to DNA breaks induced by CRISPR-Cas9, enabling unbiased detection of off-target editing in cellular and animal models. Zuo et al. identified off-targets without the interference of natural genetic heterogeneity by injecting base editors into one blastomere of a two-cell mouse embryo and leaving the other genetically identical blastomere unedited. Jin et al. performed whole-genome sequencing on individual, genome-edited rice plants to identify unintended mutations. Cytosine, but not adenine, base editors induced numerous single-nucleotide variants in both mouse and rice. Science , this issue p. 286 , p. 289 , p. 292 ; see also p. 234
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“they create new formats of off-target effects such as RNA editing and sgRNA-independent DNA editing”
From Off-target effects in CRISPR/Cas9 gene editing (2023) · cites this paper as Jin et al., 2019
In the citing paper
“Although CBE and ABE greatly reduce the classic off-target effects of CRISPR/Cas9 systems”
From Off-target effects in CRISPR/Cas9 gene editing (2023) · cites this paper as Jin et al., 2019
In the citing paper
“Previously it has been shown that cytidine but not adenine base editors result in significant, genome-wide, off-target effects57,69.”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [57]
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Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos
Zuo, E., Sun, Y., Wei, W., Yuan, T., Ying, W., Sun, H., Yuan, L., Steinmetz, L. M., Li, Y., & Yang, H. (2019) · Science · doi:10.1126/science.aav9973 · Cited by 782
Off-target effects in CRISPR/Cas9 gene editing
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“Although CBE and ABE greatly reduce the classic off-target effects of CRISPR/Cas9 systems, they create new formats of offtarget effects such as RNA editing and sgRNA-independent DNA editing (Grünewald et al., 2019; Jin et al., 2019; Zhou et al., 2019; Zuo et al., 2019).”
Background
Metadata
- Authors
- Jin, S., Zong, Y., Gao, Q., Zhu, Z., Wang, Y., Qin, P., Liang, C., Wang, D., Qiu, J.-L., Zhang, F., & Gao, C.
- Affiliations
- Chinese Academy of Sciences (CN)
- Sichuan Agricultural University (CN)
- University of Minnesota (US)
- Corresponding author
- Jin, Shuai
- Zong, Yuan
- Gao, Qiang
- Gao, Caixia
- ORCID
- Venue
- Science
- Published
- 2019-04-19
- Volume
- 364
- Issue
- 6437
- Pages
- 292-295
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2917855738
- Cited by
- 665
- References
- 34
- Citations by year
- 2026: 49 · 2025: 59 · 2024: 74 · 2023: 85 · 2022: 91 · 2021: 98 · 2020: 124 · 2019: 83
- FWCI
- 32.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (31788103)
- Chinese Academy of Sciences (QYZDY-SSW-SMC030)
- National Key Research and Development Program of China (2016YFD0101804)
- college of biological sciences, University of Minnesota startup funding
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Genetic and Mutation Studies
- Keywords
- base editors, cytosine base editors, adenine base editors, off-target mutations, single nucleotide variants, CRISPR/Cas9, genome editing, rice, single-cell whole-genome sequencing
- MeSH terms
- Gene Editing, Whole Genome Sequencing, Adenine, Cytosine, DNA Mutational Analysis, Mutation, Oryza, Polymorphism, Single Nucleotide, Agrobacterium
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