On January 25th, the research results of cloned monkeys published in Nature magazine caused a sensation at home and abroad. This achievement was developed by Sun Qiang, researcher and team of the Institute of Neuroscience, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, and realized the world. Somatic cell clone of the first non-human primate.
Figure | Clone monkeys named "Zhongzhong" and "Huahua"
Compared with the well-known cloned sheep Dolly and other clones, the greatness of this study is that the technology is more accurate and can be "produced" in batches.
Dolly is the "lucky" in more than two hundred deaths.
“China, China†and “Huahua†have lower probability of success
The timeline came back to 1997, when Nature published a study that shocked the world: the Wilmut research team at the Roslin Institute in the UK used clone technology to create a little ewe, Dolly.
This is the first sheep in the world to be cloned from matured somatic cells (breast cells) that have been differentiated.
22 years later, this scene was born in Shanghai, China. On November 27, 2017, the cloned monkey "ä¸ä¸" was born, and on December 5th, "Huahua" was born.
Like the cloned sheep "Dolly", this cloned monkey also uses somatic cells, but it is worth pointing out that although the "Dolly" cloning technology was announced at the time, overnight, cloned pigs, cloned cows, cloned mice... ... have come out, but in the study of cloning primates, they have been in a bottleneck for decades.
The previous cloned sheep "Dolly" was the lucky one of the scientists' failure of more than two hundred times. This technique used the cloning of primates, and the probability of success will be further reduced. In other words, it is difficult to conceive with cells in the natural state, and the success rate is almost negligible.
"Clone Monkey" is not a day's work
Three key technologies laid the foundation for its birth
Such a low success rate can also breed cloned monkeys. Sun Qiang, the core leader of the research team, has a great contribution.
Figure | Sun Qiang
At the undergraduate level, he studied at the Zhelim Wood Animal Husbandry College in Inner Mongolia, and then studied for a master's degree at Yangzhou University. He also got close contact with the sensational Yangzhou University cloned goat “淼淼†research, and then graduated in July 1999. He joined his doctorate at work and received his Ph.D. in June 2005.
Although this sensational world's research results have cost the team for five years, Sun Qiang's attention and research in this area will take longer.
In September 2005, Sun Qiang officially went to the Institute of Brain Functional Genomics of East China Normal University, and was responsible for the fourth sub-topic of the National Key Basic Research and Development Project “Analysis of the Establishment of Transgenic Higher Animals and Advanced Brain Function Analysis†undertaken by the brain. The study on monkey reproductive physiology and the construction of transgenic monkeys won the first batch of "test tube" cynomolgus monkeys in China.
This stage, in a strict sense, is the beginning of Sun Qiang's use of genetic technology to study primates.
In June 2009, Sun Qiang, who already has rich experience, came to the Institute of Neuroscience of the Shanghai Institute of Biological Sciences of the Chinese Academy of Sciences and was responsible for the establishment of a non-human primate model animal platform.
In the following five or six years, Sun Qiang’s research has been fruitful:
In 2013, regarding somatic cell transplantation, he published his latest technical achievements in Nature.
In 2016, he published his own achievements in non-human primate research and gene editing technology in two important international journals, Nature and Cell.
Sun Qiang evaluated his research work like this:
"For the current state of non-human primate model animal technology, we constructed a non-human primate model that overexpressed transgenes and gene knockouts using lentiviral transfection and TALEN and Crispr-cas9;
On the other hand, we also develop non-human primates due to the advantages of somatic cell nuclear transfer, semi-cloning and spermatogonial stem cell-mediated transgenes with genotype-stable single, no chimerism and one-step access to fine genetically engineered animal models. Cloning and semi-cloning techniques;
Finally, in response to the natural obstacle of non-human primate sexual maturity, we developed a technique of spermatogenesis to promote male gamete maturity, which greatly shortened the non-human primate maturity time, thus accelerating the construction of non-human primate model animals. process. â€
The above three key technologies and research mentioned by Sun Qiang laid the birth of cloned monkeys.
The birth of cloned monkeys will promote the study of human reproductive development
Non-human primates, as model animals closest to humans, have an important position in basic research and biomedical research; in the field of neuroscience, non-human primate animal models are used to study brain cognition and brain diseases. The mechanism is also crucial. However, a longer sexual maturity cycle is a major impediment to the application of non-human primate models (such as the commonly used non-human primate experimental animals - rhesus monkeys and cynomolgus monkeys, which have a sexual maturity of 4-5 years). ).
So Sun Qiang led his research team through continuous improvement experiments, based on the mastery and improvement of the micromanipulation technology of non-human primate somatic cell nuclear transfer, using gene editing technology to reprogram the cell nucleus, thereby significantly improving The blastocyst quality of somatic cell cloned embryos and the pregnancy rate of surrogate monkeys.
The high precision of the technology also makes a large number of outputs possible. "Using somatic cells to effectively perform gene editing in vitro, accurately screen somatic cells with the same genotype, and use nuclear transfer methods to produce a large number of embryos with the same genotype. The mother monkey is born with a group of genetically edited monkeys with the same genetic background. This is the key technology for making brain science research and animal models of human diseases." Sun Qiang said.
"Primers are the most similar experimental animals to humans. They are important in the study of human reproductive development and disease. It is foreseeable that the future application of genetic editing and somatic cell nuclear transfer technology in primates will certainly promote Promote the basic theory of reproductive development, the study of disease mechanisms and the development of regenerative medicine research." Ji Weizhi, an academician of the Chinese Academy of Sciences, commented.
How far is the clone?
Technical limitations and ethics are obstacles
All along, although everyone is worried about the abuse of this technology and the threat to human beings, the core reason for the current ethical problems lies in the uncontrollability of genetic mutations in the transgenic process.
Different from the previous cloning technology, the improvement of the technical precision of Sun Qiang reduced the probability of gene mutation, and the safety of the cloning technology itself was further improved.
For this achievement, Gao Shaorong, dean of the School of Life Science and Technology of Tongji University, said: "The current cloning technology is far from perfect, and we need to further explore the reprogramming mechanism. This research also reminds some scientists of ethics and Current technical limitations do not allow attempts to clone humans.
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