摘要
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(Macaca fascicularis)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 nonhuman 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.
基金
supported by the National Natural Science Foundation of China (82021001,31825018)
National Key Research and Development Program of China (2022YFF0710901)
Shanghai Municipal Science and Technology Major Project (2018SHZDZX05)
Strategic Priority Research Program of the Chinese Academy of Sciences (XDB32060100)
Biological Resources Program of Chinese Academy of Sciences (KFJ-BRP-005)
National Science and Technology Innovation 2030 Major Program 2021ZD0200900。
