CRISPR技术,血管性血友病 z-bo 2020-11-30 334

　　A research team led by Zhou Qi, a researcher at the Institute of Zoology, Chinese Academy of Sciences, used CRISPR/Cas9 technology to obtain vWF knockout pigs for the first time, thereby establishing a miniature pig model of von Willebrand disease.

　　Pig is the most important domestic animal breed in my country, and it is also an important model animal in biomedical research. Pigs are closer to humans than rodents in many physiological characteristics such as cardiovascular and gastrointestinal tracts, and their organ sizes and functions are also very similar to humans, and their litter size is high and easy to reproduce. Based on this, the detailed genome modification of pigs to establish models for studying swine epidemics or human diseases is of great value for animal husbandry production and biomedical research.

　　CRISPR/Cas9 system is easy to construct and can quickly induce mutations at multiple gene sites. It has been successful in animals such as rats and mice, but has not been applied to the research of economic animals such as pigs. By directly injecting the CRISPR-Cas system that cuts the vWF gene into the fertilized eggs of small pigs, the research team efficiently obtained surviving small pigs with biallelic mutations, confirming the applicability of CRISPR technology in large animals. Compared with the traditional “two-step method” of first performing gene knockout in somatic cells and then obtaining gene knockout pigs through somatic cell nuclear transfer, the “one-step method” of direct injection based on the efficiency and convenience of CRISPR can be faster and more convenient To obtain knockout pigs. Mutations in vWF can cause clinical type I and type III von Willebrand disease. The study further found that these knockout pigs have a clinical phenotype similar to that of patients with von Willebrand disease-severe coagulopathy. This is also the first report to use CRISPR technology to prepare a mammalian disease model with a specific disease phenotype. This research provides a new way for the rapid establishment of genetically modified animal models using pigs as objects, and will greatly promote the research on the pathogenesis and treatment methods of livestock diseases and human diseases.

　　The research was supported by the Strategic Science and Technology Pilot Program of Chinese Academy of Sciences Stem Cell and Regenerative Medicine, the Major Scientific Research Program of the Ministry of Science and Technology, and the National Natural Science Foundation of China.