TALEN-Mediated Gene Mutagenesis in Rhesus and Cynomolgus Monkeys
Open accessAbstract
Recent advances in gene editing technology have introduced the potential for application of mutagenesis approaches in nonhuman primates to model human development and disease. Here we report successful TALEN-mediated mutagenesis of an X-linked, Rett syndrome (RTT) gene, methyl-CpG binding protein 2 (MECP2), in both rhesus and cynomolgus monkeys. Microinjection of MECP2-targeting TALEN plasmids into rhesus and cynomolgus zygotes leads to effective gene editing of MECP2 with no detected off-target mutagenesis. Male rhesus (2) and cynomolgous (1) fetuses carrying MECP2 mutations in various tissues including testes were miscarried during midgestation, consistent with RTT-linked male embryonic lethality in humans. One live delivery of a female cynomolgus monkey occurred after 162 days of gestation, with abundant MECP2 mutations in peripheral tissues. We conclude that TALEN-mediated mutagenesis can be an effective tool for genetic modeling of human disease in nonhuman primates.
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Precise genome editing based on zinc finger nucleases, TALENs, or CRISPR was successfully implemented in nonhuman primates.
“More recently, precise genome editing techniques based on zinc finger nucleases, transcription activator-like endonucleases (TALENs) or CRISPR were successfully implemented in nonhuman primates26–28”
From CRISPR-based functional genomics for neurological disease (2020) · cites this paper as [27]
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- Authors
- Liu, H., Chen, Y., Niu, Y., Zhang, K., Kang, Y., Ge, W., Liu, X., Zhao, E., Wang, C., Lin, S., Jing, B., Si, C., Lin, Q., Chen, X., Lin, H., Pu, X., Wang, Y., Qin, B., Wang, F., Wang, H., Si, W., Zhou, J., Tan, T., Li, T., Ji, S., Xue, Z., Luo, Y., Cheng, L., Zhou, Q., Li, S., Sun, Y. E., & Ji, W.
- Affiliations
- Tongji University (CN)
- Kunming Institute of Zoology (CN)
- University of California, Los Angeles (US)
- Chinese Academy of Sciences (CN)
- Kunming University of Science and Technology (CN)
- Corresponding author
- Li, Siguang
- Sun, Yi Eve
- Ji, Weizhi
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2014-03
- Volume
- 14
- Issue
- 3
- Pages
- 323-328
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC4024384
- OpenAlex
- W1983005863
- Cited by
- 200
- References
- 30
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 3 · 2022: 9 · 2021: 15 · 2020: 15 · 2019: 19 · 2018: 14 · 2017: 29 · 2016: 32 · 2015: 25 · 2014: 27 · 2013: 1
- FWCI
- 15.45
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Natural Science Foundation of China (91319309, 2012AA020701, 2011CB965103, 31271599, U1302227, 90919057, 31271371)
- Tongji University
- Major State Basic Research Development Program of China
- National Institutes of Health
- National High-tech Research and Development Program (2012AA020701)
- National Key Research and Development Program of China (2011CB965103, 2012CBA01300)
- National Institute of Mental Health (R56MH082068, R01MH082068)
- National Institute on Drug Abuse (P50DA005010)
- National Institute of General Medical Sciences (P01GM081621)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P30HD004612)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Animal Genetics and Reproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- TALEN, MeCP2, Rett syndrome, X-linked disorders, rhesus monkeys, Macaca fascicularis, zygote microinjection, off-target mutagenesis, genetic disease modeling, non-human primates
- MeSH terms
- Amino Acid Sequence, Animals, Base Sequence, Endonucleases, Female, Humans, Macaca fascicularis, Macaca mulatta, Male, Molecular Sequence Data, Trans-Activators, Mutagenesis, Methyl-CpG-Binding Protein 2
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