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Choosing the Right Animal Model for COVID-19 Research

Animal models, namely human disease models, refer to animals with simulated human diseases established in various medical scientific researches. They are mainly used in experimental physiology, experimental pathology and experimental therapeutics (including new drug screening) researches, having an irreplaceable value in the research of major human diseases and the creation of new drugs.

When conducting pharmacology and pharmacodynamics studies to better develop drugs and vaccines, it is necessary to resort to animal models. If the pathogenesis of a virus in a certain animal is similar to that in humans, the clinical tests of various drugs and vaccines can be performed in animals. Such animal experiments are relatively cheap, convenient and fast, which are especially less subject to ethical or legal restrictions, with much faster research progress.

Some viral diseases have natural animal models. Rabies is a zoonotic disease that can infect all mammals, with almost the same pathogenesis. Therefore, almost all mammals can be used as the disease model of rabies, and the most commonly used ones are rats, rabbits and dogs. Rabies vaccine is the second successfully developed vaccine after smallpox vaccine, and it is also one of the most effective vaccines. Human rabies vaccines are safe and effective, which can be used in all mammals.

Some viruses specifically infect humans instead of any other animals, which have no suitable animal models, making the research and development of related drugs and vaccines difficult.

The evolution of animal disease models

In 2007, breaking through discoveries of Mario-Capecchi laid the foundation for the development of “gene targeting” technology (mice).

In 2011, Bruce Beutler et al. discovered the key principle of immune system activation (mice and fruit flies).

In 2012, Shinya Yamanaka et al. made outstanding contributions in the field of nuclear reprogramming (mice).

Meaning of using animal models of human diseases

  1. Avoidhuman experimentation
  2. Provide disease materials with low incidence
  3. Facilitate the acquisition and comparison of materials
  4. Simplify experiment operation and sample collection
  5. Contribute to a more comprehensive understanding of the nature of the disease

Animal models classified by disease types include:

  • Inducible (experimental) disease model: artificially induceanimals to produce certain human-like diseases through physical, chemical, biological and other pathogenic factors.
  • Spontaneous (hereditary) disease model: refers to a disease that occurs naturally in an animal or a disease model that is preserved through targeted breeding due to abnormal expressions of gene mutations.
  • Genetically engineered animal disease model: ananimal whose genetic traits have been artificially modified through genetic engineering. Animals can be divided into three categories based on the different means of modification: transgenic animals, gene knockout animals, and gene replacement animals.
  • Negative disease model: a model in which a certain type, variety or strain of animals does not develop a certain disease.
  • Rare disease model: an abnormality that occurs naturally in animals, which has not been found in humans before, and it is determined as a model when similar diseases appear in humans.

The SARS-CoV-2 that is currently widespread worldwide comes from wild animals, but it currently only infects humans. The construction of animal models of COVID-19 is one of the technical bottlenecks for vaccines and drugs to progress from laboratory to clinical application. According to a report in NATURE on March 12, the Institute of Medical Experimental Animals of the Chinese Academy of Medical Sciences established a genetically modified mouse model and a rhesus monkey COVID-19 disease model, and reported preliminary findings that infections of monkeys and mice contained the human ACE2 gene, which is also a protein used by the SARS-CoV-2 to enter cells. It expanded the understanding of the etiology and pathology of COVID-19, and provided indispensable support for further research on pathogenesis, transmission approaches, drug and vaccine evaluation, etc.

However, no animal model is perfect. What is often needed is not one animal model, but multiple animal models. Monkeys and mice can reveal different information about infections, which can help clarify the role of the immune system or how the virus spreads.

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