Repairing the "Spider Man" Embryo Pathogenic Gene
September 03, 2018 Source: Guangzhou Daily
Window._bd_share_config={ "common":{ "bdSnsKey":{ },"bdText":"","bdMini":"2","bdMiniList":false,"bdPic":"","bdStyle":" 0","bdSize":"16"},"share":{ }};with(document)0[(getElementsByTagName('head')[0]||body).appendChild(createElement('script')) .src='http://bdimg.share.baidu.com/static/api/js/share.js?v=89860593.js?cdnversion='+~(-new Date()/36e5)];Guangzhou Daily’s all-media reporter recently learned from the Third Affiliated Hospital of Guangzhou Medical University that the research team of Liu Jianqiao (the first author unit) and the team of Professor Huang Xingxu of Shanghai University of Science and Technology, using base editing technology, succeeded at the embryo level. The pathogenic genes of the genetic disease Marfan syndrome were repaired. The research was published on August 14th in the internationally renowned academic journal Molecular Therapy. It is reported that this is the first time that Chinese scientists have corrected the pathogenic mutations of genetic diseases on human embryos through base editing technology. This is a major progress made on the basis of attempts to reshape human embryonic DNA.
The results of this research have attracted the attention of many foreign media including the journal Science. The famous American technology magazine "Connected" commented that China has pushed base editing technology to human disease treatment more quickly.
Exploration: Editing 18 embryos to obtain 16 full normal genotypes
In the case of Mr. Liu's informed consent with Ma Fan syndrome, the Liu Jianqiao team obtained his blood and semen samples. Before the embryo editing, the team researchers first tested the cell line, made a cell model containing the relevant mutations, and studied the possibility of using genetic editing to repair the mutation. As a result, they found that the use of a base editor can efficiently achieve the repair of mutation sites, which provides data support for the repair of pathogenic mutations in Marfan syndrome at the embryonic level.
Approved by the Ethics Committee of the Third Affiliated Hospital of Guangzhou Medical University, the Center for Reproductive Medicine of the Third Hospital of Guangzhou Medical University began to carry out relevant clinical experiments. The researchers collected clinically discarded immature oocytes to mature in vitro, and then a single Ma Fan Sperm donated by patients with syndromes is injected into mature oocytes by micromanipulation, and embryos containing pathogenic mutant genes are obtained.
Later, using the validated base editing system, the researchers edited 18 fertilized eggs by micromanipulation. The results showed that 16 embryos showed a completely normal genotype after repair. In other words, the "spelling mistake" in the "FBN1" gene contained in the sperm provided by Mr. Liu was "corrected". The positions of the two bases A and G that were originally arranged incorrectly were changed like "Twisted Rubik's Cube". , successfully repaired at the embryo level.
After the research results were published internationally, they were followed by many foreign media including Science magazine. The famous American technology magazine "Connected" commented that China has pushed base editing technology to human disease treatment more quickly.
Thinking: A thought caused by a "family" of Marfan syndrome
According to Liu Jianqiao, each person's DNA has four bases, A, T, C, and G. They are like "life letters" and are put together to form a complete gene. In patients with Marfan syndrome, there is a "spelling error" in the gene "FBN1". The position of A and G is changed and arranged incorrectly, and it becomes a disease-causing gene. Because these patients are obviously taller than ordinary people, and their arms are more than the length of their arms, they are called "spider people." At present, there is still no specific medicine for this disease, and the disease is mainly corrected by surgery, but it can only alleviate the symptoms. The cost of treatment is expensive and cannot be cured. Most of the patients only live in their 50s.
Such people are not uncommon in the clinic. Last year, Liu Jianqiao discovered a family of Ma Fan syndrome. One of the family members, Mr. Liu (a pseudonym), was diagnosed with Ma Fan syndrome. Mr. Liu is less than 30 years old. According to him, his father, brother and brother’s children also inherited Marfan syndrome. According to the genetic law, if Mr. Liu has a child, at least 50% of the chances will inherit Ma Fan syndrome. He is aware of the dangers of this disease and hopes that the next generation will avoid this genetic tragedy. How to do? He found Liu Jianqiao and screened healthy embryos with the help of the third generation of IVF technology.
This "family" makes Liu Jianqiao into thinking: What can modern medicine do for patients with Ma Fan syndrome? Last year, he and the team began a new exploration: how to use the base editing technology to repair the "spider man" disease-causing gene at the embryo level?
It is safer to repair the disease-causing gene without destroying the DNA fragment.
Liu Jianqiao said that in this study, the researchers did not use the typical CRISPR/Cas9 gene editing technology, but instead used the base editor developed by David Liu Lab of Harvard University in 2016, but he did not participate in this. New research. David Liu said: "(The Liu Jianqiao team's research) is a good example of how to use the base editor to fix a well-known mutation."
The base editing system is more secure than the currently used gene editing artifact CRISPR/Cas9 technology. The use of CRISPR/Cas9 gene editing technology to repair mutant genes in normal embryos is a method of homologous recombination, in which the DNA duplex is first cleaved at the target site, and then homologous template provided by the editor is used to repair by homologous recombination. , edit the mutation site. The base editing system utilized in this new study does not require the cleavage of the DNA duplex to directly replace the mutation site. Liu Jianqiao said that there is no broken DNA double strand in the repair process, which is theoretically safer.
Through careful design, the researchers established a cell model in vitro to comprehensively analyze the effectiveness and safety. Finally, it was repaired at the embryo level, and the base editing technology was used to greatly improve the efficiency of repairing disease mutations. At the same time, no off-target was found. From the actual operation level, it was proved that the base editing technology is highly effective in repairing disease-causing mutations on human embryos. Sex and safety.
"This study provides a possible treatment idea for patients with such pathogenic mutations, demonstrating the gene therapy potential of gene editing technology." However, Liu Jianqiao admits that due to research reliability, safety verification, etc. The reason is that there is still a long way to go before clinical applications. (Reporter Weng Shuxian correspondent Bai Hao)
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