Up to now, COVID-19 viral disease caused by SARS-CoV-2 coronavirus infection has swept into at least 114 countries and was announced officially to be a pandemic by the World Health Organization on March 11, 2020. In China, a large amount of clinical resources and scientific research resources have been invested to win the war against the epidemic and protect the global human health and well-being. Among them, animal modeling of the disease has been listed as one of the five key projects to fight the current national epidemic situation.
In vitro cell models cannot simulate the in vivo pathogenesis of the diseases caused by viral infections, nor can they reflect the metabolism of drugs and the effects of viruses on multiple organs, thus the development of animal models is irreplaceable. Although monkeys and pigs can be infected with SARS-CoV-2, they generally have a long growth cycle and a large size that is difficult to handle in large quantities. However, rats and mice that are more readily available are less susceptible to SARS-CoV-2. Both SARS-CoV-2 and SARS coronavirus use ACE 2 (angiotensin-converting enzyme 2 ) as the receptor for infecting humans. Due to the significant differences at the virus interaction sites of ACE2 proteins between mice and human, mice are not susceptible to COVID-19. The key to establishing a mouse model of COVID-19 is to make the mice to express human ACE2 protein and become SARS-CoV-2 susceptible. This goal can be achieved through biotechnology methods such as transgene technique and humanization. Humanization technology is a new-generation of animal model technology that has emerged in recent years, with better accuracy but greater challenges as well. It usually takes at least half a year to obtain animals as quickly as possible, holding back its application in the current epidemic. Therefore, researchers face serious challenging in selecting animal models for drug screening and pathology research.
In the afternoon of March 12, the News Office of the People's Government of Guangdong Province held a press conference to announce the current COVID-19 situation and recent research progress on COVID-19 in Guangdong. At the meeting, Prof. Guangming Wu, a researcher from the Center for Cell Lineage and Atlas (CCLA) of the Guangzhou Regenerative Medicine and Health Guangdong Laboratory (also referred to as the Bioisland Laboratory), announced their success in establishing the ACE2 humanized mice in 35 days. Prof. Wu introduced that shortly after the epidemic outbreak in January, the Guangzhou Regenerative Medicine and Health Guangdong Laboratory and the Guangzhou Institutes of Biomedicine and Health of the Chinese Academy of Sciences (hereinafter referred to as the Guangzhou Health Institute) organized multiple joint projects to fight the disease. As one of the projects, CCLA initiated promptly the animal modeling project on January 31st, led by Prof. Jiekai Chen and Prof. Guangming Wu, by integrating the relevant scientific research forces from both teams. On March 6th, after overcoming many key technique barriers, the ACE2 humanized mice were born successfully. This achievement used a combination of the unique tetraploid embryo compensation technique and innovative stem cell technology in the lab and shortened the time to generate the ACE2 humanized mice from the usual 6 months to only 5 weeks.
The ACE2 humanized mice is an ideal animal model for the researches of COVID-19 on pathogenesis, drug screening, and vaccine evaluation.