How do three generations of Spiderman have healthy offspring?
——Guangdong scientists modify the pathogenic gene to correct the common genetic disease
Reporter of jinyang.com
One out of every 5000 people in the world has Marfan syndrome, which is also known as “Spider Man” because of its uneven limbs, fingers and toes. This disease can affect almost all parts of the body, there is no specific treatment, surgery can only reduce symptoms, can not cure, and the cost is expensive. Most of the patients died in their 50s, and some even died in their 30s.
How do these patients give birth to healthy babies? On August 29, the reporter learned from the Third Affiliated Hospital of Guangzhou Medical University that Professor Liu Jianqiao’s research team and Professor Huang xingxu’s team of Shanghai University of science and technology successfully repaired the pathogenic gene of the genetic disease Marfan syndrome (MFS) at the embryonic level by using base editing technology. The research results have been published in the international academic journal Molecular Therapy on August 14.
This is the first time for Chinese scientists to correct the pathogenic mutation of genetic diseases in human diploid embryos through base editing technology, which represents a significant progress on the basis of the attempt to reshape the DNA of human embryos, and preliminarily proves the efficiency and safety of base editing technology in the repair of pathogenic mutation in human embryos.
If any one of the parents is ill, the child is most likely to be inherited
According to Liu Jianqiao, the study originated from a special case: a young man in his 20s, his father, his brother and his brother’s son are all Marfan syndrome. In order to have a healthy child, he came to see a doctor.
Marfan syndrome is an autosomal dominant genetic disease, which is caused by a single base mutation of gene “FBN1”. Liu Jianqiao introduced that if any one of the parents is a homozygous mutation of Marfan syndrome, that is, the two alleles are mutant genes, the child will be 100% inherited; if both sides are heterozygous mutations, one of the two alleles mutates and the other is normal, the child will have a 75% genetic probability; if one side is heterozygous mutation, the other side is not a patient, the child will be 50% inherited. After testing, this young man is heterozygous mutation, if the child at least 50% of the probability of genetic Marfan syndrome.
Gene re editing makes most embryos repair perfectly.
“DNA is like a rope ladder. Marfan syndrome is one of the first steps. The two fixed points on the left and right are reversed, causing mistakes.” According to reports, everyone’s DNA is composed of a, t, C, G four bases, they constitute a gene through different combinations. In Marfan syndrome patients, the key gene “FBN1”, a and G positions have been changed.
In fact, last March, Liu Jianqiao’s team published for the first time in the world the application of gene editing technology to normal human embryos. They used CRISPR / cas9 gene editing technology to edit the gene of diploid embryos fertilized normally in order to block the two genetic diseases of thalassemia and broad bean disease in Guangdong.
Can gene editing technology be used to repair the gene mutation of Marfan syndrome at the embryonic level? After obtaining the informed consent of the patient, the research team, with the help of the blood and sperm donated by the patient, started the research of using gene editing technology to modify the pathogenic gene of Marfan syndrome in human embryos.
Liu Jianqiao’s team adopted the base editor developed by David Liu Laboratory of Harvard University in 2016. The researchers collected the clinical discarded immature oocytes for in vitro maturation, and then injected the sperm donated by the patient into the mature oocytes through micromanipulation to obtain the fertilized eggs containing heterozygous pathogenic mutation gene.
Before these fertilized eggs began to divide, the team used a base editing system to edit 18 embryos by micromanipulation. The results showed that in addition to two cases of embryos were not perfectly repaired, the remaining 16 embryos showed completely normal genotypes! In the control group, 4 out of 7 embryos were normal genotypes, and 3 out of 7 embryos contained 50% pathogenic mutations. What’s more encouraging is that the operation of this gene editing technology is not “off target” after sequencing identification, which proves its safety and reliability.
Due to ethical limitations, there is still a long way to go from clinical practice
Liu Jianqiao said that the base editing technology is relatively safe, “it does not need double strand DNA cutting, nor the insertion of foreign genes, but in situ modification at the mutation site.” It can be seen as a more efficient and safe way to correct spelling mistakes.
It is understood that at present, base editing technology can only repair single base mutation. In addition to Marfan syndrome, β – thalassemia, a disease with high incidence in Guangdong, also belongs to single base mutation.
“This study provides a possible treatment for patients with such pathogenic mutations and demonstrates the potential of gene editing technology for gene therapy.” Liu Jianqiao said. However, he also stressed that due to ethical issues and limitations of relevant laws and regulations, as well as research reliability and safety verification, this technology is still far from clinical application.