First Successful Offspring Created Through the Cloning of A Non-Human Primate

By 2017, researchers were able to successfully clone and produce offspring from 23 different types of mammalian species. However, they remained unable to clone non-human primates; the most important species for studying human disease. Using the information gathered from many failed experiments, researchers from the Institute of Neuroscience Chinese Academy of Science were able to successfully generate offspring using non-human primate cloning. In order to generate the clones, researchers first had to optimize the somatic cell nuclear transfer (SCNT) of the clonal DNA into a fertilized egg. This optimization was due to the common cloning issue of inappropriate reprograming of somatic nuclei for fetal development. The optimization process included removal of oocyte spindle chromosome complex's, incubation of donor cell with viral envelope, and donor cell insertion into perivitelline space. Next, the embryos were treated with the histone deacetylase inhibitor trichostatin A in order to improve overall blastocyst efficiency. In order to combat reprogramming resistant region (RRRs) which contain a high level of histone 3 lysine 9 trimethylation, the human dementhylase KDM4d/4a was also added to the fused embryos. The combination of these optimization procedures ensures that donor DNA is able to efficiently enter into the enucleated egg and generate a healthy developing fetus. Lastly, the authors decided to try to generate clones using adult somatic DNA as well as fetal money fibroblast DNA, despite assuming that fetal DNA would be much easier to reprogram and generate a new fetus. As expected, their optimized SCNT protocol using fetal monkey DNA was not only able to impregnate adult female cynomolgus monkeys, but generate two happy and heathy baby macaques named Zhong Zhong and Hua Hua.

Reference

• Liu, Zhen, et al. Cloning of Macaque Monkeys by Somatic Cell Nuclear Transfer. Cell (2018).

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