She is Yang Luhan, known as the ‘Gene Scissors’, a true scholar who graduated from Peking University-Harvard.
CRISPR ‘cut out’ Piglet pathogenic gene
You must know that pigs are one of the best animals for human organ transplantation.
There are two major risks in transplanting pig organs into humans:
On the one hand, pigs are genetically engineered to carry endogenous retroviruses (PERVs), pig organs on the other hand produce rejection in humans.
5 years ago, Yang Luhan led the team to successfully use CRISPR- Cas9 ‘gene scissors’ technique inactivates disease-causing genes in pig cells.
This studyInactivation of porcine endogenous retrovirus in pigs using CRISPR-Cas9 It was published in the journal Science on August 10, 2017.
Paper link: https://www .science.org/doi/abs/10.1126/science.aan4187
In previous research work, most of the genetic modification was done at a gene level. The scientific problem faced by Yang Luhan’s team is how to modify 62 genes in a single cell of pigs, that is, endogenous retroviruses (PERVs).
More importantly, the integrity of the genome is also guaranteed.
Yang Luhan used the CRISPR-Cas9 gene editing tool to overcome this problem, which not only greatly improved the efficiency of gene editing, but also shortened the time for breeding genetically modified pigs.
As can be seen, all pigs achieved essentially 100% clearance of endogenous retrovirus at baseline mRNA levels.
Note: Brown is 1 Day old piglets; Blue are 5-7 days old piglets; Green are 15-19 days old piglets
In the study, the scientists also searched for PERVs present in the genome of porcine fibroblasts, and found a total of 25 species. They also used CRISPR technology to inactivate the genetic loci of these 25 PERVs.
This is a The only born PERV-inactivated piglet, named LaiKa, was photographed on the second day after birth.
is Yang Luhan The contribution of the team’s CRISPR-Cas9 gene knockout technology has fundamentally solved the risk of viral infection caused by transplanting pig organs into humans.
But this goddess scientist’s research doesn’t stop there. Just as the well-known ‘graphene driver’ Cao Yuan is a madman of Nature, Yang Luhan can be called a madman of Science and Nature.
Two weeks Big PERV inactivated piglets
Actually As early as 2013, Yang Luhan successfully applied the CRISPR system to human cell gene editing, which was also published in the international journal Science.
paper Link: https://www.science.org/doi/10.1126/science.1232033
In 2015, Yang Luhan published a paper on the work of CRISPR-Cas9 to modify genes in cells as the co-first author in Science.
Paper link: https://www.science.org/doi/10.1126/science.aad1191
September 2020, an articleExtensive germline genome engineering in pigs The paper was published in Nature and successfully developed the first-generation xenotransplantation prototype ‘Pig 3.0’ that can be used in clinic.
Paper link: https://www.nature.com/articles/s41551-020-00613-9
In December last year, it was published in the domestic core journal “Organ Transplantation”. You can also see Yang Luhan’s name. The author is Hangzhou Qihan Biotechnology Co., Ltd. .
The study explored the application prospects of gene-edited pigs in xenotransplantation. The researchers knocked out a porcine endogenous retrovirus (PERV), combined with the knockout of 3 major xenogeneic antigen genes, and transferred 9 humanized genes that inhibit complement activation, regulate coagulation disorders, and anti-inflammatory and anti-phagocytosis. Pigs (PERV-KO/3-KO/9-TG) were used as donors, and their hearts, livers and kidneys were obtained and transplanted to three rhesus monkey recipients to establish a preclinical research model of pig-monkey xenotransplantation.
The research results show that gene-edited pigs (PERV-KO/3-KO/9-TG) have certain advantages in overcoming hyperacute rejection, relieving humoral rejection and coagulation disorders , but whether it can be used as a potential donor for clinical xenotransplantation needs further evaluation.
The Xueba in the eyes of others
Yang Luhan born in the 1980s , is a native Sichuan girl.
In 1986, she was born in a small county town of Bashu with beautiful landscapes. Her father was a civil servant and her mother was an accountant.
Since she was a child, Luhan has always been called ‘other people’s child’ by our parents. Self-discipline and hard work are her labels.
‘How can there be any genius, just one more effort than others. ‘There is also no shortcut to Yang Luhan’s success.
Yang Luhan once said,
When I was a child, my parents were very busy, and my mother was not in good health. I didn’t want them to worry about it since I was a child, and I worked very hard. My studies are not always good, if you ask my classmates, they may say that Luhan works hard! In fact, like most people, it is very difficult.
At the age of 15, she ranked first in the high school entrance examination in Mount Emei He was admitted to Chengdu No. 7 Middle School.
From the second year of high school, she joined the biology competition team and completed all the undergraduate and postgraduate courses of the biology department in one year. She basically relied on self-study.
At that time, Yang Luhan often went to Sichuan University to listen, she said that she could hardly understand.
‘ read two or three times and you will understand. ‘This kind of self-study is a real test of self-discipline and self-study ability for a high school student.
Hard work pays off, Luhan overcame many difficulties with talent and hard work, and successfully participated in the International Biology Olympiad.
In 2004, Luhan won the gold medal in the 15th International Biology Olympiad on behalf of China.
Naturally, she was admitted to the School of Life Sciences of Peking University to continue her studies.
In 2008, after obtaining a double bachelor’s degree in life sciences and psychology, Luhan went to Harvard University for further studies, where she continued her master’s and doctoral studies, and carried out post-doctoral research.
Since then, this young female scientist has embarked on a scientific research road that is inseparable from genetics.
Learning from the ‘Father of Synthetic Biology’ George Church
As the saying goes, a famous teacher produces a great apprentice, and Yang Luhan’s progress in genetic research cannot be separated from the correct guidance of her mentor.
Her supervisor, Dr. George Church, is a professor of genetics at Harvard Medical School, known as the “Father of Synthetic Biology”, and a dual academician of the National Academy of Sciences and the National Academy of Engineering.
Research areas include genome sequencing and data analysis, synthetic biology, genome engineering, personal genomics, etc.
Professor George Church was predicted to be expected to win the Nobel Prize. Previously, he has won the scientific achievements of Franklin Bauer. In 2017, he was also selected as the most influential in the world by “Time” magazine. One of the top 100 people.
As early as 1984, George Church published the first direct genome sequencing method as the first author and the second author of the mentor Walter Gilbert.
In an interview in 2017, when talking about what the next big breakthrough in genetic science would be, Professor George Church believed that it was ‘writing’ DNA, not ‘editing’ it.
Professor George Church believes that ‘writing DNA’ includes adding genes, deleting genes (or reducing gene expression) and precise editing, and finally can write what you want anywhere you want Gene.
When adding a gene, the gene can be inserted into any position of the chromosome. When deleting or downgrading a gene, either introduce an interfering molecule or directly attack the gene and make a mess. There are few ways to completely remove a gene.
Almost didn’t graduate from Harvard
Back in 2015 , Yang Luhan started her entrepreneurial journey and co-founded a biotechnology company called eGenesis with her mentor George Church.
This is a company dedicated to advancing the clinical application of xenotransplantation, and she is also the Chief Scientific Executive of eGenesis.
After returning to China in 2017, Yang Luhan officially became the CEO of Hangzhou Qihan Biotechnology Co., Ltd.
In the same year, Yang Luhan was selected as the 2017 ‘Young Global Leader’ by the World Economic Forum in Davos. In September 2020, he was selected as one of Fortune’s 2020 ‘Global 40 Business Elites Under 40’.
What people see is Yang Luhan’s success and her halo, but people may not know that she almost didn’t graduate from Harvard University.
April 2018, Vancouver, Canada, Yang Luhan was rehearsing backstage at TED2018
When she was studying in high school, Yang Luhan delayed her English learning because she was busy with the Biology Olympiad, resulting in her poor English grades.
Studying in a foreign country, because of language difficulties, it is difficult for her to carry out in-depth professional studies, and even the qualifying exam for Harvard University seems powerless.
Therefore, she was required to take a one-year language course in order to remain at Harvard.
She couldn’t ‘waste’ a minute or a second in the lab until her English improved.
Fortunately, Professor George Church said that he could understand what Yang Luhan wanted to express.
As a tutor, Professor George Church does not let his students waste time on language.
During the whole postgraduate period, almost every week, Yang Luhan will have academic discussions with her supervisors, and also exchange various topics of science, culture and society.
‘ It was Professor George Church who restored my faith! ‘Looking back on the past, Yang Luhan was deeply moved.
Professor George Church taught her far more than academics, but taught her how to be a truly great leader.
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