Generation of mitochondrial replacement monkeys by female pronucleus transfer

Mutations in mitochondrial DNA (mtDNA) are maternally inherited and have the potential to cause severe disorders. Mitochondrial replacement therapies, including spindle, polar body, and pronuclear transfers, are promising strategies for preventing the hereditary transmission of mtDNA diseases. While...

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Veröffentlicht in:Dōngwùxué yánjiū 2024-03, Vol.45 (2), p.292-298
Hauptverfasser: Li, Chun-Yang, Liu, Xing-Chen, Li, Yu-Zhuo, Wang, Yan, Nie, Yan-Hong, Xu, Yu-Ting, Zhang, Xiao-Tong, Lu, Yong, Sun, Qiang
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container_title Dōngwùxué yánjiū
container_volume 45
creator Li, Chun-Yang
Liu, Xing-Chen
Li, Yu-Zhuo
Wang, Yan
Nie, Yan-Hong
Xu, Yu-Ting
Zhang, Xiao-Tong
Lu, Yong
Sun, Qiang
description Mutations in mitochondrial DNA (mtDNA) are maternally inherited and have the potential to cause severe disorders. Mitochondrial replacement therapies, including spindle, polar body, and pronuclear transfers, are promising strategies for preventing the hereditary transmission of mtDNA diseases. While pronuclear transfer has been used to generate mitochondrial replacement mouse models and human embryos, its application in non-human primates has not been previously reported. In this study, we successfully generated four healthy cynomolgus monkeys ( ) via female pronuclear transfer. These individuals all survived for more than two years and exhibited minimal mtDNA carryover (3.8%-6.7%), as well as relatively stable mtDNA heteroplasmy dynamics during development. The successful establishment of this non-human primate model highlights the considerable potential of pronuclear transfer in reducing the risk of inherited mtDNA diseases and provides a valuable preclinical research model for advancing mitochondrial replacement therapies in humans.
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Mitochondrial replacement therapies, including spindle, polar body, and pronuclear transfers, are promising strategies for preventing the hereditary transmission of mtDNA diseases. While pronuclear transfer has been used to generate mitochondrial replacement mouse models and human embryos, its application in non-human primates has not been previously reported. In this study, we successfully generated four healthy cynomolgus monkeys ( ) via female pronuclear transfer. These individuals all survived for more than two years and exhibited minimal mtDNA carryover (3.8%-6.7%), as well as relatively stable mtDNA heteroplasmy dynamics during development. 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apes</topic><topic>Mutation</topic><topic>Primates</topic><topic>Primates - genetics</topic><topic>Pronucleus</topic><topic>Rodent Diseases</topic><topic>Sperm</topic><topic>Stem cells</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Li, Chun-Yang</creatorcontrib><creatorcontrib>Liu, Xing-Chen</creatorcontrib><creatorcontrib>Li, Yu-Zhuo</creatorcontrib><creatorcontrib>Wang, Yan</creatorcontrib><creatorcontrib>Nie, Yan-Hong</creatorcontrib><creatorcontrib>Xu, Yu-Ting</creatorcontrib><creatorcontrib>Zhang, Xiao-Tong</creatorcontrib><creatorcontrib>Lu, Yong</creatorcontrib><creatorcontrib>Sun, Qiang</creatorcontrib><creatorcontrib>中国科学院大学, 北京 100049, 中国</creatorcontrib><creatorcontrib>Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, China</creatorcontrib><creatorcontrib>Key Laboratory of Genetic Evolution and Animal Models, Chinese Academy of Sciences, Kunming 650201, China</creatorcontrib><creatorcontrib>University of Chinese Academy of Sciences, Beijing 100049, China</creatorcontrib><creatorcontrib>中国科学院神经科学研究所脑科学与智能技术卓越创新中心, 神经科学重点实验室, 上海 200031, 中国</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health &amp; 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subjects Animal models
Animals
Disease transmission
DNA, Mitochondrial - genetics
Embryos
Female
Females
Genetic testing
Genomes
Haplorhini - genetics
Heteroplasmy
Humans
Menstruation
Mice
Mitochondria
Mitochondria - genetics
Mitochondrial Diseases - genetics
Mitochondrial Diseases - prevention & control
Mitochondrial Diseases - veterinary
Mitochondrial DNA
Monkeys
Monkeys & apes
Mutation
Primates
Primates - genetics
Pronucleus
Rodent Diseases
Sperm
Stem cells
title Generation of mitochondrial replacement monkeys by female pronucleus transfer
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