Zhong Zhong (中中) and Hua Hua (=华华+)
Cloning of Macaque Monkeys by Somatic Cell Nuclear Transfer
Liu et al.
Cell, VOLUME 172, ISSUE 4, pp.881-887.E7, FEBRUARY 08, 2018
Published: January 24, 2018 DOI:https://doi.org/10.1016/j.cell.2018.01.020
Zhen Liu, Yijun Cai, Yan Wang, Yanhong Nie, Chenchen Zhang, Yuting Xu, Xiaotong Zhang, Yong Lu, Zhanyang Wang, Muming Poo, Qiang Sun
• Somatic cell nuclear transfer (SCNT) using fetal fibroblasts yielded two live monkeys
• Epigenetic modulators promoted development and pregnancy rate of SCNT embryos
• SCNT using adult cumulus cells yielded live births of monkeys that were short-lived
• Genetic analysis confirmed the clonal origin of the SCNT monkey offspring
Generation of genetically uniform non-human primates may help to establish animal models for primate biology and biomedical research. In this study, we have successfully cloned cynomolgus monkeys ( Macaca fascicularis) by somatic cell nuclear transfer (SCNT).
We found that injection of H3K9me3 demethylase Kdm4d mRNA and treatment with histone deacetylase inhibitor trichostatin A at one-cell stage following SCNT greatly improved blastocyst development and pregnancy rate of transplanted SCNT embryos in surrogate monkeys.
For SCNT using fetal monkey fibroblasts,
6 pregnancies were confirmed
in 21 surrogates
and yielded 2 healthy babies.
For SCNT using adult monkey cumulus cells,
22 pregnancies were confirmed
in 42 surrogates
and yielded 2 babies that were short-lived.
In both cases, genetic analyses confirmed that the nuclear DNA and mitochondria DNA of the monkey offspring originated from the nucleus donor cell and the oocyte donor monkey, respectively. Thus, cloning macaque monkeys by SCNT is feasible using fetal fibroblasts.
Zhong Zhong (Chinese: 中中; pinyin: Zhōng Zhōng, born 27 November 2017) and Hua Hua (Chinese: 华华; pinyin: Huá Huá, born 5 December 2017) are a pair of identical crab-eating macaques (also referred to as cynomolgus monkeys) that were created through somatic cell nuclear transfer (SCNT)
Chinese scientists create cloned primates that could revolutionize studies of human disease.
Nature 553, 387-388 (2018)
Biologists in Shanghai, China, have created the first primates cloned with a technique similar to the one used to clone Dolly the sheep and nearly two dozen other species. The method has failed to produce live primates until now.
Researchers hope to use this revised technique to develop populations of genetically identical primates to provide improved animal models of human disorders, such as cancer. The technology, described in Cell on 24 January, could also be combined with gene-editing tools such as CRISPR–Cas9 to create genetically engineered primate-brain models of human disorders, including Parkinson’s disease.
“This paper really marks the beginning of a new era for biomedical research,” says Xiong Zhi-Qi, a neuroscientist who studies brain disease at the Chinese Academy of Sciences Institute of Neuroscience (ION) in Shanghai. He was not involved in the cloning project.
But the achievement is also likely to raise some concerns among scientists and the public that the technique might be used to create cloned humans. “Technically, there is no barrier to human cloning,” says ION director Mu-Ming Poo, who is a co-author of the study. But ION is interested only in making cloned non-human primates for research groups, says Poo: “We want to produce genetically identical monkeys. That is our only purpose.”
Primates have proved tricky to copy, despite many attempts using the standard cloning technique. In that method, the DNA of a donor cell is injected into an egg that has had its own genetic material removed.
ION researchers Sun Qiang and Liu Zhen combined several techniques developed by other groups to optimize the procedure. One trick was to undo chemical modifications in the DNA that occur when embryonic cells turn into specialized cells. The researchers had more success with DNA from fetal cells, rather than cells from live offspring.
Using fetal cells, they created 109 cloned embryos, and implanted nearly three-quarters of them into 21 surrogate monkeys. This resulted in six pregnancies. Two long-tailed macaques (Macaca fascicularis) survived birth: Zhong Zhong, now eight weeks old, and Hua Hua, six weeks. Poo says that the pair seem healthy so far. The institute is now awaiting the birth of another six clones.
Cloning specialist Shoukhrat Mitalipov of the Oregon Health and Science University in Portland says that the Chinese team should be congratulated. “I know how hard it is,” says Mitalipov, who estimates he used more than 15,000 monkey eggs in cloning attempts in the 2000s. Although he was able to produce stem-cell lines from cloned human and monkey embryos, his team’s primate pregnancies never resulted in a live birth.
Cloned animals offer some significant advantages over non-clones as models for studying human disease. In experiments with non-cloned animals, it is difficult to know whether differences between the test and control groups were caused by the treatment or genetic variation, says Terry Sejnowski, a computational neurobiologist at the Salk Institute for Biological Studies in La Jolla, California. “Working with cloned animals greatly reduces the variability of the genetic background, so fewer animals are needed,” he says.
Sejnowski also says that primate brains are the best model for studying human mental disorders and degenerative diseases. The ability to clone monkeys might revive primate studies, which have declined in most countries, says Poo. Parkinson’s disease experiments that currently use hundreds of monkeys could be done with just ten clones, he says.
Neuroscientist Chang Hung-Chun, also at ION, says that primate-cloning technology will soon be combined with gene-editing tools to study human genetic disorders in primate brains. Gene editing is already used on developing monkey embryos, but that leaves open the possibility that some cells are not edited, which then affects the results, says Chang.
With cloning, the donor cell can be edited before it is injected into the egg. Within a year, Poo expects the birth of cloned monkeys whose cells have been genetically edited to model circadian-rhythm disorders and Parkinson’s disease.
Spurred by the promise of primate research, the city of Shanghai is planning major funding for an International Primate Research Center, expected to be formally announced in the next few months. The centre will produce clones for scientists around the globe. “This will be the CERN of primate neurobiology,” Poo says. There’s already high demand from pharmaceutical companies that want to use cloned monkeys to test drugs, he says.
Although most reproductive biologists are unlikely to consider using the technique to clone humans because of ethical objections, Mitalipov worries that it might be attempted in a private clinic.
China has guidelines that prohibit reproductive cloning, but no strict laws. It also has a weak record of enforcement of its rules on the use of stem cells for therapy. Some other countries — notably the United States — do not prohibit reproductive cloning at all. “Only regulation can stop it now,” says Poo. “Society has to pay more attention to this.”
Nature 553, 387-388 (2018)
[Cloned monkeys to be used for brain disease research]
BEIJING - A new research base in Shanghai will be dedicated to monkey cloning and neuroscience studies with results to advance the research of human brain diseases, according to a report of Science and Technology Daily on Thursday.
In January, scientists from the Institute of Neuroscience (ION) under the Chinese Academy of Sciences (CAS) successfully cloned two macaques from somatic cells, regarded as a breakthrough in neuroscience and a great opportunity for brain disease research.
Based on monkey cloning technology, the CAS Center for Excellence in Brain Science and Intelligence Technology (CEBSIT) launched the base in Songjiang district of Shanghai on Wednesday, with plans to develop and eventually commercialize key neuroscience technologies. It also aims to create leading enterprises in neuroscience and artificial intelligence.
Muming Poo, director of CEBSIT and ION, was quoted as saying that the center is aimed at becoming an international center for nonhuman primate disease modeling research and a national center for brain intelligence technology research and transformation.
In the base, interdisciplinary research and development teams will use somatic cell cloning and transgenic technology to establish brain disease models, paving the way for the development of new drugs for brain diseases such as Alzheimer's disease and autism, the newspaper said.