Model animal "made in China" new drug research and development "pioneer"


 Science and Technology Daily reporter Zhangjiaxing

      Open the heavy lid, liquid nitrogen vaporized Baiwuniaonuo. Looking through the fog along the liquid nitrogen tank, a tightly arranged tube is visible in the liquid nitrogen tank. "There are nearly 3,000 gene-engineered animal systems here. Technologist Zhangyuan lifted up some of the silos in the fog. The liquid nitrogen contained animals ' "seeds" -- fertilized egg cells or sperm cells whose internal genomes had been specifically modified.
     Correspondingly, a row of "Biography" lines are neatly displayed in the information room not far away. On April 23, on the eve of the "Wuhan International Academic Conference on Liver Metabolism and Cardiovascular Diseases" sponsored by Wuhan University Basic Medical College and Wuhan University's Institute of Model Animals, a reporter from the Science and Technology Daily visited the Wuhan University Institute of Model Animals(hereinafter referred to as the Model Animal Institute). Discover, Every pattern here is well documented. Random copies of thousands of books are taken from the pages, detailing the construction of each model animal and its daily evolution.
     Here, the team once "ran" with foreign countries and became one of the first teams to establish a gene knockout model rat system; Here, foreign counterparts come looking for large model animals of stable quality for new drug trials.
      It is not too late to create more than 40 disease models to catch the "late episode"

      In the strategic study of the key consulting projects of the Chinese Academy of Engineering issued in 2016, the chapter on experimental animal science in China wrote: The resources are seriously insufficient, less than 1/10 of developed countries; Technology is lagging behind, at least 30 years behind developed countries.

      Since the 1980s, foreign countries have long been engaged in the establishment of genetic knock-out animal models for the development of new drugs. "The United States has filed tens of thousands of patents for the most mature model animal mice. At that time, there was no CRISPR's "magic shear" technology. The stable cultivation of embryonic stem cells was a prerequisite for model animals. The use of gene editing techniques such as zinc fingerase also required a complex technical system.
       The model animal research team is keenly aware that model animals are a "fate" of gene sequences from "Tianshu" to application. It's not too late to catch the "late episode". The "track" of the mouse strain patent has been occupied, but the rat embryonic stem cell line has not been successfully established, so there is still a chance. In the past 10 years, the team has continued to independently or cooperate in research and development. At present, it has owned nearly 3,000 genetic engineering and mouse strains, established more than 40 standardized animal models of diseases, and provided model animals for more than 1,000 research institutions and pharmaceutical research and development institutions at home and abroad. Made in China.
       It is not difficult to simulate a "consistency" in simulation
       The quality assurance of model animals is best suited to apply the phrase "It is not difficult to do a good deed, but it is difficult to do a good deed for a lifetime" -- it is not difficult to simulate a "consistency" in simulation.
       A new drug, right? To answer this question, you should first look at the efficacy of the sick animal. How do you make animals sick? It doesn't sound that hard. However, it is difficult to get a group of animals to suffer from the same disease with the same degree and overlapping symptoms.

        In industrial manufacturing, machine production is still difficult to achieve the same quality, not to mention for living creatures with diversity of life?

      The secret of the model animal is, talent. "I need to ligate this mouse's aorta to cause vascular stenosis, and after a period of time, this mouse will show signs of myocardial hypertrophy. "While explaining to the science and technology daily reporter, while flexibly turning the tweezers in his hand, a thread thinner than the hair thread is stuck on a certain blood vessel. In less than five minutes, Tiansong had made a perfect "knot" on the skin of the mouse's chest and ended an animal model surgery that simulated human disease.
      The "One Knife" doctors of the Zhongnan Hospital attached to Wuhan University were invited by the Model Animal Institute to come to the surgery class for the technicians. Their philosophy is that model animals must withstand the verification of quality uniformity and withstand the strict test of drug trials. The spirit to "mold".
Target-oriented primates must be 'different'
      When the industry thought that the model animal service drug test could only be a "mouse model," the model animal agency found another way.

      Non-human primates are closest to humans clinically, most able to simulate various human diseases, and monkeys are ideal as a drug screening model. Our country experiment monkey is rich in resources, there are more than 3 00000 monkeys in the column, if used reasonably, it will become an important resource of our country's drug research and development. The Institute of Model Animals of Wuhan University has established a variety of disease models including fatty liver, liver, and heart ischemia and reperfusion injury on monkeys using dietary induction, surgery, and gene editing techniques, and selects new compounds based on this model. Two of the drug molecules have completed pharmacological experiments and toxicological evaluations on monkeys. The data is ideal and is advancing clinical transformation. It is expected to be used to treat liver and heart damage.

       The team believes that in simulating human diseases, the traditional gene knockout monkey technology route may not be successful. For example, knocking a gene on a mouse can lead to high blood pressure, but knocking the same gene on a monkey can lead to many other diseases besides high blood pressure. The higher the organism, the more "part-time" genes are, so it is difficult to have a single factor to control the perfect primate disease model.
So shouldn't we give up? The goal orientation led the team to innovate in thought-to achieve local organ gene editing on monkeys. For example, the team explored the combination of gene encapsulation and high-pressure injection, allowing the genome in a monkey's organ tissue to absorb target fragments and partially express or inhibit the effect of the target gene.
      "Model animals are to be able to produce steadily and can be used." In order to allow normal animals to simulate the "thousands of sickness" of life, the team is also deeply cultivating basic research and "touching the pathways and mechanisms of cells." Based on an in-depth understanding of ubiquitin ligase, receptor factors, etc., a variety of model animal production methods were established. According to statistics, innovations in the exploration of technical methods and disease mechanisms have enabled the team to apply for more than 150 invention patents at home and abroad, of which nearly 60 have been approved, all of which are invention-type patents.
      Model animals are a "hub" that links genes to diseases and is a "pioneer" in the development of new drugs. In this field, the research on the basic theory of the left hand of the model animal research institute of Wuhan University, the exploration of the clinical application of the right hand, and the use of artisan spirit to steadily explore a path of medical application of life science.
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