The birth of the world's first somatic cell clone monkey is of great significance for the study of human diseases.

Release date: 2018-01-26

Recently, the research team of the Institute of Neuroscience and the Center for Excellence in Brain Science and Intelligent Technology of the Chinese Academy of Sciences announced the latest major breakthrough. After five years of research, the research team successfully cloned two macaques, which is the world's first somatic cell cloning technology. The birth of primates is of great significance for the construction of non-human primate models and the study of human diseases.

At present, this major scientific achievement has been published as a cover article in the international authoritative academic journal Cell, and the editor of the journal Cell is an exciting and important work. A technological milestone that has only been achieved in years, it has the potential to revolutionize animal research and help develop new ways to treat human diseases.

It is understood that two cloned monkeys were born on November 27 and December 5, 2017, and were named "中中" and "Huahua". The key to their birth is somatic cell cloning technology. A DNA-containing core of an adult cell is implanted into an egg cell (nucleated) to reprogram the DNA to an embryonic state.

Specifically, the research team used a miscarriage of female macaque fetus as a material to extract the nuclei of somatic cells (non-germ cells) and inject the nuclei into the egg cells by means of microinjection techniques. The macaques developed from this recombinant egg have the same genetic characteristics as the nuclear donor. Therefore, in addition to slightly different heads, “中中” and “华华” are almost identical in appearance. After growing up to six months, “中中” and “华华” will be sent to the monkey group. Observe its status in group life.

"中中" and "Huahua"

In 1997, the first individual cell nuclear transfer cloned animal, Dolly, was born. In the following 20 years, many mammalian somatic cell clones succeeded, not only the birth of large livestock such as horses, cattle, sheep, pigs and camels. A variety of experimental animals such as mice, rats, rabbits, and cats have been born, but the problem of somatic cell clones of non-human primates that are most similar to humans has not been solved and has become a worldwide problem.

Clone sheep dolly

For a long time, many scientific research institutions such as the United States, China, Germany, Japan, Singapore, and South Korea have been exploring and experimenting in this area, but they have not succeeded. However, it is worth mentioning that in 1999, Professor Gerald Schatten of the Oregon National Primate Research Center successfully cloned a rhesus monkey by means of embryonic division, but did not attract widespread attention because it did not use somatic cell nuclear transfer technology. In addition, Professor Shoukhrat Mitalipov of the National Primate Center in Oregon and Calvin Simerly of the University of Pittsburgh also attempted to clone non-human primates using somatic cell nuclear transfer technology.

Non-human primate somatic cell cloning history, picture source: Sun Qiang

So, where is the difficulty of non-human primate nuclear transfer?

"The main difficulty is in three aspects, taking macaque as an example: First, the monkey cell nucleus is opaque, difficult to identify, and difficult to denucleate; second, the monkey's oocyte is easy to activate in advance, and the operation is slightly careless, and the oocyte may be Activation, then it will start the autologous cleavage, the somatic cells can not keep up, and finally the egg can not develop; the third is the monkey's somatic cell clone embryo development is poor, the culture blastocyst is low efficiency, the proportion of high quality blastocyst is low. Sun Qiang, director of the non-human primate research platform of the Institute of Neuroscience, Chinese Academy of Sciences, said.

Without cloning monkeys, it is difficult to establish an animal model that mimics human disease. Currently, a common animal model for drug development is mice. However, mice are far from humans. Drug developers have spent a lot of resources on mouse models, but the selected drug candidates are used on patients, but they are mostly ineffective or have unacceptable side effects, which makes them such as Alzheim. Brain diseases such as silent disease and autism, as well as immunodeficiency, tumors, and metabolic diseases cannot be effectively treated. Therefore, non-human primate models are urgently needed for life science research and human disease research.

To this end, under the leadership of Academician Pu Muming, the nerve of the Chinese Academy of Sciences, Sun Qiang led a team led by post-doctor Liu Zhen. After five years of unremitting efforts, he successfully broke through the frontier of this biology.

In order to minimize the impact on cells, the researchers came up with the use of polarized light to "light" the cells. The operation must be completed in a very short time. Dr. Liu Zhen spent a lot of time training this. The technology finally achieved the micromanipulation of somatic cell nuclear transfer in 10 seconds.

In addition, the researchers continue to experiment with various experimental methods to promote somatic cell nuclear reprogramming through epigenetic modification, significantly improving the blastocyst quality of somatic cloned embryos and the pregnancy rate of surrogate monkeys.

Simple flow chart of cloning monkeys, picture from cell

Bai Chunli, president of the Chinese Academy of Sciences, said: "The results of this research have truly realized the overtaking of cornering in the field of life sciences, which is of great significance."

It is understood that the success of the success of "Zhongzhong" and "Huahua" is that it can produce a large number of model monkeys with the same genetic background within one year, and effectively edit the genes in vitro by using somatic cells to accurately screen. The somatic cells with the same genotype are then used to generate a large number of embryos with the same genotype by nuclear transfer. The mother monkey is born with a batch of genetically edited and genetically identical monkeys. This is an animal model for brain science research and human disease. The key technologies will greatly promote the basic research of life sciences and the development of translational medicine.

At the same time, the creation of a disease model based on somatic cell cloned monkeys will effectively shorten the drug development cycle, improve the success rate of drug development, and promote brain diseases such as Alzheimer's disease and autism, as well as immunodeficiency, tumor and metabolism. The development of new drugs for diseases has promoted the development of a new pharmaceutical R&D industrial chain based on animal models of non-human primate diseases.

The birth of cloned monkeys has brought ethical questions while bringing significant research significance. Some people have suggested that cloned monkeys are coming out, will clones be far behind?

Pu Muming, director of the Institute of Neuroscience of the Chinese Academy of Sciences, made it clear: "The purpose of doing cloning monkeys is to establish animal models to help understand the human brain and treat various diseases of human beings. It is not necessary to conduct cloning studies, but society. The ethics also does not allow cloning.

He also stressed: "Any scientific discovery is a double-edged sword. It may bring great progress, and it may cause a series of crises. Nuclear energy and genetic editing are typical examples. The ethical issues of life science are not just scientists' needs. Attention, it is more necessary for government departments and the entire public to participate in the process of restricting people's behavior and making correct decisions through legislation and legislation."

Source: Medical Valley

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