In the fight against the epidemic in early 2020, in just 35 days, a humanized ACE2 mouse model was established, and researcher Guangming Wu and his colleagues from the Center for Cell Fate and Lineage Research (CCLA) at Bio-Island Laboratories successfully made a major breakthrough using stem cell technology to create a "fight against New Coronary Pneumonia". A miracle of speed in an emergency attack.
A sudden test
In August 2019, Wu Guangming, a long-time researcher in the field of embryonic development, returned to Guangzhou from Germany to join the first batch of "Guangdong Province to build a national laboratory reserve team" of the Bio-Island Laboratory, namely the Guangzhou Guangdong Laboratory of Regenerative Medicine and Health.
What he didn't expect was that it wouldn't be long before he had to face the unexpected test of a new crown pneumonia outbreak.
"The research field I am engaged in actually has nothing to do with infectious diseases, but in the face of the oncoming epidemic, after learning that the Guangdong Provincial Department of Science and Technology had set up a special project for emergency research on the new crown pneumonia epidemic, I wondered what I could do to fight the epidemic when the whole country was working together."
Through understanding, Wu Guangming found that humanized animal models are urgently needed for the diagnosis and treatment of the new coronavirus as well as for its long-term control. The so-called humanized animal model is to make animals (monkeys, mice, etc.) with certain characteristics of human tissues, organs, and cells through gene editing and other methods to construct disease models, study the pathogenic mechanisms of human diseases and find the best treatment solutions.
The attack was completed in 35 days
Wu Guangming told the reporter that there were only in vitro cell models at that time and many people were anxious. He happened to have many years of experience in transgenic animal research and was also good at tetraploid compensation technology. One of his research ideas back then was to fuse embryonic stem cell technology and embryonic tetraploid compensation technology together to establish humanized mouse models, and it was encouraging that the Center for Cell Fate and Genealogy Research at Bio Island Laboratories then had the leading stem cell technology, and it seemed that all external conditions were ripe.
Thinking is one thing, doing is another.
How difficult is it to build up a usable mouse model? Under normal processes, it would take at least six months and go through countless trial and error processes. But in the face of an emergency epidemic, one needs to race against time and hang on to the map.
The team was formed on an ad hoc basis because most of the people had already gone home for the Chinese New Year. Finally, eight people who remained in Guangzhou were found under the Center for Cell Fate and Genealogy Research organization to form a temporary humanized mouse model attack team.
From the design of the experimental protocol on January 31 to the birth of the first generation of humanized mice on March 6, the team accomplished this miracle of scientific research in only 35 days. Conventional technology requires mixing mouse stem cells and embryos to obtain chimeric mice, and only when the stem cells differentiate into germ cells and then mate with other mice to pass the edited genes to the next generation of mice can they be considered successful. The humanized mice from CCLA were born to obtain the target knock-in mice at once, gaining valuable time and saving manpower and material resources for anti-epidemic.
Wu Guangming at work Photo/provided by the interviewee
All working overtime
Wu Guangming admitted that at the beginning, no one's heart had a bottom, and the tetraploid technology itself was extremely difficult, with a success rate of less than 2%.
At that time, all the people were fully devoted to the research, regardless of day and night, without working days and weekends. Every day at 3:00 or 4:00 a.m., the team members discussed the day's progress; they chatted until dawn and immediately went back to another day of research.
As the technical leader of the research team, Wu Guangming has to balance two aspects of work - gene editing and embryo culture - and has to follow every step of the experimental process and solve problems in a timely manner, which is more stressful than one can imagine.
At that time, due to the Spring Festival holiday and the epidemic, all the reagents needed were out of stock, and we had to find people everywhere to borrow them. The daily work was testing, experimenting, sending samples and looking for reagents.
In order to rush the time, the research team broke the normal state of the experimental process, while early preparation of each subsequent experimental step. But this also means that if something goes wrong in the previous steps, the subsequent steps are prepared in vain.
However, biological experiments themselves are a process that requires constant trial and error.
Wu Guangming still remembers that once, the in vitro vector was used to insert into the cellular DNA sequence, but it did not work, so he had to adjust the reagent concentration and other parameters over and over again and do it again and again until it worked.
The work was so stressful that everyone was overworked, some members had blisters in their mouths, and some were so tired that they could only squat on the floor to talk because they just couldn't stand up.
For success, Wu Guangming, however, even said that he was lucky to meet a group of outstanding teammates, and it was great to finish the construction of the mouse model in such a short time.
Still want to further improve
On March 6, 17 first-generation humanized mice were successfully born. However, this could only be described as the first step in the completion of the work, which was quickly followed by a rigorous validation process and the sending of the humanized mice to the P3 lab for successful virus testing.
However, Wu Guangming also thought of further improvements to the mouse model.
He told reporters that 80% of patients with COVID-19 are asymptomatic or mildly ill, meaning that they can rely on their own immunity to recover, while the other 20% of patients develop severe disease, mostly in the elderly or those with underlying diseases. Therefore, in order to more accurately and effectively use mouse models for pathology, drug, and vaccine research, the team is targeting humanized mice plus premature aging, diabetes, hypertension, and other underlying disease models to establish a severe disease mouse model.
Looking back on the intense work, Wu Guangming said he was proud of such a team, where everyone understood the importance of what they were doing, had a high level of awareness, and worked hard to achieve such results.
Related news links: "Guangdong War Epidemic To Honor Heroes" Wu Guangming's team: 35 days to establish ACE2 humanized mouse model (baidu.com)
Post time: Aug-02-2023