Combatting COVID-19 with Help from Genetically Engineered Mice

In Brief

  • Genetically engineered mouse models that can react to COVID-19 the same way humans do are playing a key role in the development of vaccines.
  • Mice have been used in biomedical research dating back to 1678, including in the annual development of influenza vaccinations.
  • To create a genetically engineered mouse model specific to SARS-CoV-2, scientists used an adenovirus based vector that was altered to carry a specific DNA or RNA message to a host.
  • So far, three vaccines have been approved, including two that use the new mRNA platform.

On January 19, 2020, a 35-year-old man from Washington state visited a local urgent care clinic, where doctors conducted numerous scans and tests. He was admitted to Providence Regional Medical Center after testing positive for COVID-19. Simultaneously, a tiny dot appeared on a map of COVID-19 cases. While this man was one of the first known coronavirus cases in the U.S., within a matter of weeks, maps of several regions of the country turned completely red, depicting the rising number of cases.

While three COVID-19 vaccines are currently being administered, with the latest receiving FDA approval in late February, efforts to develop additional candidates remain in the pipeline. In the past, it has usually taken 10 to 15 years for vaccine development. This lengthy process helps ensure safety and effectiveness.

In Dr. Mike Diamond’s lab, located at Washington University in St. Louis, Dr. Brett Case, a postdoctoral researcher and his colleagues are hard at work conducting SARS-CoV-2 studies. To Dr. Case, coronavirus research is not unfamiliar. He uses his past knowledge from studying coronaviruses in Mark Denison’s laboratory at Vanderbilt University to provide insight on this specific strain. Although he has significant prior experience, this virus is still different from other previously known coronaviruses.

Dr. Case and his colleagues began accelerating efforts to develop vaccinations and treatments for the virus. To accurately conduct this research, Dr. Case first needed genetically engineered mice models that can react to the virus the same way humans do. These models are generally preferred due to lower costs and relatively easy genetic manipulation.

Mice have been used in biomedical research dating back to 1678, including in the annual development of influenza vaccinations. To create a genetically engineered mouse model specific to SARS-CoV-2, Dr. Case used an adenovirus based vector. Adenoviruses are known to have minimal consequences. They are altered to carry a specific DNA or RNA message to a host. Once it is delivered in the cell, the message is transformed into a protein. This adenovirus is engineered, since the original evaluated mice models don’t replicate the severe lung disease phenotypes that have been observed in hospitalized cases. The engineered adenovirus tells the cell how to make the human ACE2 receptor (which is what SARS2 uses to get into cells). Now mice symptoms will reflect humans and the mice can be used to accurately model the efficacy and safety of possible vaccines.

“The adenovirus cannot replicate so it’s not a big deal to the mouse. After a few days, when we inoculate with SARS2, the receptor is ready and available on the surface of the mouse cells for the virus to use to gain entry,” according to Dr. Case.

The development and administration of the Moderna and Pfizer vaccines, the first two coronavirus vaccines to be approved, have made scientific history. This is because they are mRNA vaccines, a completely new vaccination platform.

It’s not that “viruses are necessarily hard to work with, it’s just a matter of how fast you need to get results or move…Finding the specific cell type that it can replicate in… is always a bit of a process. When you’re trying to move extremely fast, that can be a little challenging,” according to Dr. Case.

Yet, with the help of mouse models, researchers and the biomedical research companies they work for have achieved what seemed impossible throughout much of 2020: safe and effective COVID-19 vaccines.

Content expert

Dr. Brett Case, Ph.D is a postdoctoral research scholar at the Washington University in St. Louis Medical School. He is currently working in the Diamond Laboratory, studying the new coronavirus while trying to develop a vaccine.

 


Sources

 

Bhandari, Tamara. “Lab-Made Virus Mimics COVID-19 Virus.” Washington University School of Medicine in St. Louis, 24 Aug. 2020,   medicine.wustl.edu/news/lab-made-virus-mimics-covid-19-virus/.

Holshue, Michelle L., et al. “First Case of 2019 Novel Coronavirus in the United States: NEJM.” New England Journal of Medicine, 7 May 2020,   www.nejm.org/doi/full/10.1056/NEJMoa2001191.

Katella, Kathy. “5 Things Everyone Should Know About the Coronavirus Outbreak.” Yale Medicine, 27 Aug. 2020,   www.yalemedicine.org/stories/2019-novel-coronavirus/.

Nazario, Brunilda. “How Many Coronavirus Strains Are There? Novel Coronavirus Types and More.” WebMD, WebMD, 5 May 2020,   www.webmd.com/lung/coronavirus-strains#1.

The New York Times. “Coronavirus in the U.S.: Latest Map and Case Count.” The New York Times, The New York Times, 3 Mar. 2020,   www.nytimes.com/interactive/2020/us/coronavirus-us-cases.html.

“Vaccine Development, Testing, and Regulation.” History of Vaccines,   www.historyofvaccines.org/content/articles/vaccine-development-testing-and-regulation.


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Image credits: Bebe Lemanowicz


This article was written by Muskan Paliwal. Muskan and the cSw student editing team would like to thank Brandon Levy for serving as a mentor on this story. Brandon Levy is a Science Communications Editor for the Intramural Research Program (IRP) at the National Institutes of Health (NIH). As always, before leaving a response to this article please view our Rules of Conduct. Thanks! -cSw Editorial Staff

Muskan Paliwal

Author: Muskan Paliwal

Muskan Paliwal is a junior at West Windsor Plainsboro High School South in the greater Princeton area of New Jersey. She is a Co-Founder and Vice President of her school’s HOSA - Future Health Professionals chapter, as well as a volunteer at her local hospital and Red Cross. She is interested in pursuing a career in health science in the future.

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