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Generation of a Nonhuman Primate Model of Severe Combined Immunodeficiency Using Highly Efficient Genome Editing

Published on Jul 1, 2016in Cell Stem Cell21.46
· DOI :10.1016/j.stem.2016.06.003
Kenya Sato3
Estimated H-index: 3
(Central Institute for Experimental Animals),
Ryo Oiwa5
Estimated H-index: 5
(Central Institute for Experimental Animals)
+ 23 AuthorsErika Sasaki20
Estimated H-index: 20
(Central Institute for Experimental Animals)
Abstract
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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  • References (55)
  • Citations (40)
References55
Newest
#1Yu Kang (Kunming University)H-Index: 8
#2Bo Zheng (Nanjing Medical University)H-Index: 8
Last.Hong Wang (Kunming University)H-Index: 9
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#1Yongchang Chen (Kunming University of Science and Technology)H-Index: 11
#2Yinghui Zheng (CAS: Chinese Academy of Sciences)H-Index: 3
Last.Ruxiao Xing (CAS: Chinese Academy of Sciences)H-Index: 3
view all 15 authors...
#1Zhen Liu (CAS: Chinese Academy of Sciences)H-Index: 11
#2Xue Zhou (CAS: Chinese Academy of Sciences)H-Index: 1
Last.Yijun Cai (CAS: Chinese Academy of Sciences)H-Index: 7
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#1Tsukasa Takahashi (Central Institute for Experimental Animals)H-Index: 1
#2Kisaburo Hanazawa (Juntendo University)H-Index: 10
Last.Tomoo Eto (Central Institute for Experimental Animals)H-Index: 7
view all 14 authors...
#1Hailiang Liu (Tongji University)H-Index: 11
#2Yongchang Chen (KIZ: Kunming Institute of Zoology)H-Index: 11
Last.Shaoyun Lin (Tongji University)H-Index: 1
view all 32 authors...
#1Yuyu NiuH-Index: 15
#2Bin Shen (National Resource Center)H-Index: 14
Last.Jiahao Sha (Nanjing Medical University)H-Index: 33
view all 28 authors...
Cited By40
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#1Sho Yoshimatsu (Keio: Keio University)H-Index: 1
#2Junko Okahara (Central Institute for Experimental Animals)H-Index: 5
Last.Hideyuki Okano (Keio: Keio University)H-Index: 110
view all 9 authors...
#1Wakako Kumita (Central Institute for Experimental Animals)H-Index: 2
#2Kenya Sato (Central Institute for Experimental Animals)H-Index: 3
Last.Yasubumi Sakakibara (Keio: Keio University)H-Index: 29
view all 13 authors...
#1Takahiko Noro (Central Institute for Experimental Animals)H-Index: 9
#2Kazuhiko NamekataH-Index: 24
Last.Xiaoli GuoH-Index: 17
view all 0 authors...
#1Yu Kang (Kunming University of Science and Technology)
#2Chu Chu (Kunming University of Science and Technology)
Last.Yuyu Niu (Kunming University of Science and Technology)H-Index: 15
view all 0 authors...
#1Sho Yoshimatsu (Keio: Keio University)H-Index: 1
#2Mari Nakamura (Keio: Keio University)
Last.Hideyuki Okano (Keio: Keio University)H-Index: 110
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