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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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. |
doi_str_mv | 10.24272/j.issn.2095-8137.2023.287 |
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) 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.</description><identifier>ISSN: 2095-8137</identifier><identifier>ISSN: 0254-5853</identifier><identifier>DOI: 10.24272/j.issn.2095-8137.2023.287</identifier><identifier>PMID: 38485499</identifier><language>eng</language><publisher>China: Kunming Institute of Zoology, The Chinese Academy of Sciences</publisher><subject>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</subject><ispartof>Dōngwùxué yánjiū, 2024-03, Vol.45 (2), p.292-298</ispartof><rights>Copyright Kunming Institute of Zoology, The Chinese Academy of Sciences Mar 2024</rights><rights>Copyright © 2024 Editorial Office of Zoological Research, Kunming Institute of Zoology, Chinese Academy of Sciences. 2024 Editorial Office of Zoological Research, Kunming Institute of Zoology, Chinese Academy of Sciences</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38485499$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><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><title>Generation of mitochondrial replacement monkeys by female pronucleus transfer</title><title>Dōngwùxué yánjiū</title><addtitle>Zool Res</addtitle><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.</description><subject>Animal models</subject><subject>Animals</subject><subject>Disease transmission</subject><subject>DNA, Mitochondrial - genetics</subject><subject>Embryos</subject><subject>Female</subject><subject>Females</subject><subject>Genetic testing</subject><subject>Genomes</subject><subject>Haplorhini - genetics</subject><subject>Heteroplasmy</subject><subject>Humans</subject><subject>Menstruation</subject><subject>Mice</subject><subject>Mitochondria</subject><subject>Mitochondria - genetics</subject><subject>Mitochondrial Diseases - genetics</subject><subject>Mitochondrial Diseases - prevention & control</subject><subject>Mitochondrial Diseases - veterinary</subject><subject>Mitochondrial DNA</subject><subject>Monkeys</subject><subject>Monkeys & apes</subject><subject>Mutation</subject><subject>Primates</subject><subject>Primates - genetics</subject><subject>Pronucleus</subject><subject>Rodent Diseases</subject><subject>Sperm</subject><subject>Stem cells</subject><issn>2095-8137</issn><issn>0254-5853</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNpdkUFv2zAMhXVYsQZt_sJgdJdekkq0ZEm7FEXRtQMy7LKdBdmmF2W2lEl2gfz7KU0arD2RIB8fHvERcsXoEjhIuNksXUp-CVSLhWKlzB2US1DyA5mdhudknpKrqcg9BVZ9JOel4kpwrWfk-yN6jHZ0wRehKwY3hmYdfBud7YuI2942OKAfiyH4P7hLRb0rOhxsj8U2Bj81PU6pGKP1qcN4Sc462yecH-sF-fX14ef902L14_Hb_d1q0ZS8GhdSVIpZChVYLXTNheSibgEq29ZKIwPstASkjDJmdcWtQF1LVXZKtxJAlhfk9uC7neoB2yYHjLY32-gGG3cmWGfebrxbm9_h2bBsKank2eH66BDD3wnTaAaXGux76zFMyYAWCnTOJbL08zvpJkzR5_9MyShngiqhs-rLQdXEkFLE7pSGUfNCy2zMnpbZgzF7MGZPy2Ra-fjT__-cTl85lf8ARWKVMg</recordid><startdate>20240318</startdate><enddate>20240318</enddate><creator>Li, Chun-Yang</creator><creator>Liu, Xing-Chen</creator><creator>Li, Yu-Zhuo</creator><creator>Wang, Yan</creator><creator>Nie, Yan-Hong</creator><creator>Xu, Yu-Ting</creator><creator>Zhang, Xiao-Tong</creator><creator>Lu, Yong</creator><creator>Sun, Qiang</creator><general>Kunming Institute of Zoology, The Chinese Academy of Sciences</general><general>Science Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>BVBZV</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>F1W</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H95</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>L.G</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PATMY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PYCSY</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20240318</creationdate><title>Generation of mitochondrial replacement monkeys by female pronucleus transfer</title><author>Li, Chun-Yang ; Liu, Xing-Chen ; Li, Yu-Zhuo ; Wang, Yan ; Nie, Yan-Hong ; Xu, Yu-Ting ; Zhang, Xiao-Tong ; Lu, Yong ; Sun, Qiang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c346t-75681a0262a959b45745bd226adb89e12ef972e01011a964a5e9b783f89d72273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Animal models</topic><topic>Animals</topic><topic>Disease transmission</topic><topic>DNA, Mitochondrial - genetics</topic><topic>Embryos</topic><topic>Female</topic><topic>Females</topic><topic>Genetic testing</topic><topic>Genomes</topic><topic>Haplorhini - genetics</topic><topic>Heteroplasmy</topic><topic>Humans</topic><topic>Menstruation</topic><topic>Mice</topic><topic>Mitochondria</topic><topic>Mitochondria - genetics</topic><topic>Mitochondrial Diseases - genetics</topic><topic>Mitochondrial Diseases - prevention & control</topic><topic>Mitochondrial Diseases - veterinary</topic><topic>Mitochondrial DNA</topic><topic>Monkeys</topic><topic>Monkeys & 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 & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>Agricultural & Environmental Science Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>Proquest Central</collection><collection>Natural Science Collection</collection><collection>East & South Asia Database</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ASFA: Aquatic Sciences and Fisheries Abstracts</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) 1: Biological Sciences & Living Resources</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Aquatic Science & Fisheries Abstracts (ASFA) Professional</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Environmental Science Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Environmental Science Collection</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Dōngwùxué yánjiū</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Li, Chun-Yang</au><au>Liu, Xing-Chen</au><au>Li, Yu-Zhuo</au><au>Wang, Yan</au><au>Nie, Yan-Hong</au><au>Xu, Yu-Ting</au><au>Zhang, Xiao-Tong</au><au>Lu, Yong</au><au>Sun, Qiang</au><aucorp>中国科学院大学, 北京 100049, 中国</aucorp><aucorp>Institute of Neuroscience, Center for Excellence in Brain Science and Intelligence Technology, State Key Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, China</aucorp><aucorp>Key Laboratory of Genetic Evolution and Animal Models, Chinese Academy of Sciences, Kunming 650201, China</aucorp><aucorp>University of Chinese Academy of Sciences, Beijing 100049, China</aucorp><aucorp>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</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Generation of mitochondrial replacement monkeys by female pronucleus transfer</atitle><jtitle>Dōngwùxué yánjiū</jtitle><addtitle>Zool Res</addtitle><date>2024-03-18</date><risdate>2024</risdate><volume>45</volume><issue>2</issue><spage>292</spage><epage>298</epage><pages>292-298</pages><issn>2095-8137</issn><issn>0254-5853</issn><abstract>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.</abstract><cop>China</cop><pub>Kunming Institute of Zoology, The Chinese Academy of Sciences</pub><pmid>38485499</pmid><doi>10.24272/j.issn.2095-8137.2023.287</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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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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