Genetically modified mouse models to help fight COVID-19.

Area of Science:

• * Virology and Immunology
• * Genetics and Genomics
• * Preclinical Disease Modeling

Background:

• * Understanding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection mechanisms is critical for developing effective therapies and vaccines for coronavirus disease 2019 (COVID-19).
• * A significant hurdle in COVID-19 research is the lack of appropriate preclinical animal models, as wild-type mice are naturally resistant to SARS-CoV-2 infection.
• * Mice are extensively used in biomedical research, and genetic modification tools are readily available for them.

Purpose of the Study:

• * To address the need for suitable animal models in COVID-19 research.
• * To propose the development of genetically engineered mouse models (GEMMs) that express human ACE2, enabling SARS-CoV-2 infection.
• * To outline versatile GEMM designs for advancing SARS-CoV-2 research and therapeutic development.

Main Methods:

• * Leveraging existing genetic tools for mouse modification.
• * Designing models to express human angiotensin-converting enzyme 2 (ACE2) to facilitate viral entry.
• * Proposing three broad categories and over two dozen specific designs for GEMMs.

Main Results:

• * Genetically engineered mice expressing human ACE2 are susceptible to SARS-CoV-2 infection.
• * The proposed models provide a platform for studying viral pathogenesis and testing interventions.
• * A diverse range of GEMM designs can be created to model various aspects of COVID-19.

Conclusions:

• * Genetically engineered mouse models are essential for overcoming the limitations of wild-type mice in SARS-CoV-2 research.
• * These models will accelerate the understanding of COVID-19 molecular mechanisms, drug repurposing, and vaccine development.
• * The proposed GEMMs offer a valuable resource for the global research community in the fight against COVID-19.