【Animal Modeling】-How to use CRISPR-Cas9 to construct a new animal model of a lethal virus?

  Middle East Respiratory Syndrome Coronavirus (MERS-CoV) is a new type of highly pathogenic coronavirus that has emerged in recent years. Since it was first discovered in the Middle East in 2012, its traces have been found in many European countries. The disease can cause severe lung disease, accompanied by clinical symptoms, such as fever, cough, acute respiratory distress syndrome (ARDS), and even multiple organ failure. The case fatality rate is about 36%. Acute respiratory distress syndrome model caused by MERS-because all small animals traditionally used to study the cause of viruses, such as

  Mice, hamsters, guinea pigs and ferrets all have natural resistance to MERS-CoV. obtain. CoV disease Therefore, in the latest study, researchers at the University of North Carolina at Chapel Hill used CRISPR-Cas9 gene editing technology to modify the mouse genome to establish a MERS-CoV-induced acute respiratory distress syndrome model for research. The development of new treatment techniques paved the way.

  The research results were published in the November 28th issue of "Nature Microbiology". Acute respiratory distress syndrome causes serious diseases inside and outside the lungs, causing diffuse damage to pulmonary capillaries and increasing permeability. This is usually a typical symptom of the development of advanced acute lung injury. 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, so that the mouse was affected by MERS-CoV. Infect and replicate, making it easier to receive.

  The researchers then allowed the edited mouse to produce a virus suitable for the mouse. It can replicate effectively in the lungs and may cause severe ARDS symptoms, such as reduced survival rates, sudden weight loss, and decreased lung function. More importantly, the researchers tested the effectiveness of treatments such as MERS-CoV neutralizing antibody therapy and MERS-CoV protein vaccine on this manipulated mouse.