Rapid generation of mouse model for emerging infectious disease with the case of severe COVID-19

Cheng Pu Sun, Jia Tsrong Jan, I. Hsuan Wang, Hsiu Hua Ma, Hui Ying Ko, Ping Yi Wu, Tzu Jiun Kuo, Hsin Ni Liao, Yu Hua Lan, Zong Lin Sie, Yen Hui Chen, Yi An Ko, Chun Che Liao, Liang Yu Chen, I. Jung Lee, Szu I. Tsung, Yun Ju Lai, Ming Tsai Chiang, Jian Jong Liang, Wen Chun LiuJing Rong Wang, Joyce Pei Yi Yuan, Yin Shiou Lin, Yi Ching Tsai, Shie Liang Hsieh, Chia Wei Li, Han Chung Wu, Tai-Ming Ko, Yi Ling Lin*, Mi Hua Tao


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15 引文 斯高帕斯(Scopus)


Since the pandemic of COVID-19 has intensely struck human society, small animal model for this infectious disease is in urgent need for basic and pharmaceutical research. Although several COVID-19 animal models have been identified, many of them show either minimal or inadequate pathophysiology after SARS-CoV-2 challenge. Here, we describe a new and versatile strategy to rapidly establish a mouse model for emerging infectious diseases in one month by multi-route, multi-serotype transduction with recombinant adeno-associated virus (AAV) vectors expressing viral receptor. In this study, the proposed approach enables profound and enduring systemic expression of SARS-CoV-2-receptor hACE2 in wild-type mice and renders them vulnerable to SARS-CoV-2 infection. Upon virus challenge, generated AAV/hACE2 mice showed pathophysiology closely mimicking the patients with severe COVID-19. The efficacy of a novel therapeutic antibody cocktail RBD-chAbs for COVID-19 was tested and confirmed by using this AAV/hACE2 mouse model, further demonstrating its successful application in drug development.

頁(從 - 到)1-27
期刊PLoS Pathogens
出版狀態Published - 8月 2021


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