Generation of a Nonhuman Primate Model of Severe Combined Immunodeficiency Using Highly Efficient Genome Editing
Open accessAbstract
Recent advances in genome editing have facilitated the generation of nonhuman primate (NHP) models, with potential to unmask the complex biology of human disease not revealed by rodent models. However, their broader use is hindered by the challenges associated with generation of adult NHP models as well as the cost of their production. Here, we describe the generation of a marmoset model of severe combined immunodeficiency (SCID). This study optimized zinc-finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) to target interleukin-2 receptor subunit gamma (IL2RG) in pronuclear stage marmoset embryos. Nine of 21 neonates exhibited mutations in the IL2RG gene, concomitant with immunodeficiency, and three neonates have currently survived from 240 days to 1.8 years. Our approach demonstrates highly efficient production of founder NHP with SCID phenotypes, with promises of multiple pre-clinical and translational applications.
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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 [28]
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- Authors
- Sato, K., Oiwa, R., Kumita, W., Henry, R., Sakuma, T., Ito, R., Nozu, R., Inoue, T., Katano, I., Sato, K., Okahara, N., Okahara, J., Shimizu, Y., Yamamoto, M., Hanazawa, K., Kawakami, T., Kametani, Y., Suzuki, R., Takahashi, T., Weinstein, E. J., Yamamoto, T., Sakakibara, Y., Habu, S., Hata, J.-I., Okano, H., & Sasaki, E.
- Affiliations
- Keio University (JP)
- Central Institute for Experimental Animals (JP)
- Hiroshima University (JP)
- Juntendo University (JP)
- Medical Proteoscope Co., Ltd. (Japan) (JP)
- Tokai University (JP)
- National Sagamihara Hospital (JP)
- Corresponding author
- Okano, Hideyuki
- Sasaki, Erika
- ORCID
- Venue
- Cell Stem Cell
- Publisher
- Elsevier BV
- Published
- 2016-07
- Volume
- 19
- Issue
- 1
- Pages
- 127-138
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- OpenAlex
- W2463680085
- Cited by
- 159
- References
- 55
- Citations by year
- 2026: 2 · 2025: 6 · 2024: 17 · 2023: 5 · 2022: 12 · 2021: 28 · 2020: 26 · 2019: 22 · 2018: 19 · 2017: 17 · 2016: 5
- FWCI
- 10.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 371 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Strategic Research Program for Brain Science
- Agency for Medical Research and Development (AMED), Japan
- Japan Science and Technology Agency
- Japanese Cabinet Office
- 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 › Virus-based gene therapy research
- Keywords
- severe combined immunodeficiency, nonhuman primate model, marmoset, IL2RG, zinc finger nucleases, TALEN, genome editing, neonatal survival, immunodeficiency
- MeSH terms
- Transcription Activator-Like Effector Nucleases, Gene Editing, Aging, Animals, Animals, Newborn, Blastomeres, Breeding, Callithrix, Disease Models, Animal, Embryo, Mammalian, Fibroblasts, Humans, Male, Mosaicism, Phenotype, Spermatozoa, Reproducibility of Results, Zinc Fingers, Severe Combined Immunodeficiency, Genome, Founder Effect, Interleukin Receptor Common gamma Subunit, Gene Knockout Techniques
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