CRISPR–Cas9,动物模型 z-bo 2020-12-03 344

　　Middle East respiratory syndrome coronavirus (MERS-CoV) is a new type of highly pathogenic coronavirus that has emerged in recent years. It was first identified in the Middle East in 2012 and subsequently found in several European countries. Trace of it. This disease can cause severe lung disease in humans. The clinical manifestations are fever, cough, acute respiratory distress syndrome (ARDS), and even multiple organ failure. The fatality rate is about 36%. Since small animals traditionally used to explore the pathogenesis of viruses, such as mice, hamsters, guinea pigs, and ferrets, have natural resistance to MERS-CoV, it is difficult to obtain models of acute respiratory distress syndrome caused by MERS-CoV disease. Therefore, in the latest study, researchers from the University of North Carolina at Chapel Hill used CRISPR–Cas9 gene editing technology to modify the mouse genome and construct a MERS-CoV-induced acute respiratory distress syndrome model for the development of new treatments Technology paved the way.

　　 Acute respiratory distress syndrome can cause serious diseases both inside and outside the lungs, causing diffuse damage to lung capillaries and increased permeability, which is generally a typical manifestation of acute lung injury in the later stages. In this article, the researchers used CRISPR–Cas9 technology to modify two nucleotides (288 and 330) in the mouse genome to match the human dipeptidyl peptidase 4 receptor, allowing mice to MERS-CoV infection and replication are susceptible.

　　 Later, the researchers allowed the edited mice to produce a mouse-adapted virus, which can replicate effectively in their lungs and produce severe ARDS symptoms, such as reduced survival rates, sudden weight loss, and reduced lung function. More importantly, the researchers verified the effectiveness of treatment methods such as MERS-CoV neutralizing antibody therapy or MERS-CoV protein vaccine on this engineered mouse.