A somatic cell cloned rhesus monkey by trophoblast replacement

Cloning of cynomolgus monkeys (Macaca fascicularis) has been achieved through somatic cell nuclear transfer (SCNT), which is the only cloned non-human primate (NHP). Here, we found that severe calcification of the placenta of SCNT fetuses occurred by histological examination, and loss of imprinting of some of the maternally imprinted genes in the cloned embryos by multi-omics analysis. To overcome these defects in the placenta of cloned primates, we thus developed a trophoblast replacement (TR) method, providing a placenta from ICSI-derived embryo for the SCNT fetus, to support the full-term development of the cloned NHP after implantation. By combining this TR method with treatment that overcome the epigenetic barrier for pre-implantation development, we obtained a healthy somatic cell cloned rhesus (Macaca mulatta) monkey, representing the successful cloning of a new NHP species. Together, we develop a new strategy for the cloning of primates and demonstrate its effectiveness by cloning a rhesus monkey.