This technology employs genetically modified mouse strains that express the human ACE2 receptor along with additional genetic modifications to monitor COVID-19 spike protein-induced effects. One strain incorporates a p16-luciferase reporter system that facilitates non-invasive in vivo fluorescence detection of cellular senescence, while another uses a p16-tdTomato marker, allowing red fluorescence visualization associated with senescence. Two additional strains are engineered with targeted gene knockouts—Smad3 elimination to disable the canonical TGF-β pathway and Fancd2 removal to compromise homologous recombination-mediated DNA repair. These features enable researchers to directly observe and quantify specific cellular responses, including oxidative stress and DNA damage, induced by spike protein binding.
Description
What differentiates this approach is its comprehensive ability to dissect multiple pathological pathways concurrently. By combining receptor expression with distinct reporter and knockout strategies, the models provide a nuanced platform for tracking senescence, isolating non-canonical cytokine signaling, and assessing DNA repair deficiencies. This multipronged strategy offers a refined tool for screening therapeutic agents, delivering a level of specificity and adaptability that surpasses traditional single-pathway models and enhancing overall insights into COVID-19-associated cellular damage.
Applications
- COVID-19 drug screening assays
- Cellular senescence imaging research
- TGF-β inhibitor testing
- DNA damage intervention evaluation
- Oxidative stress modulation analysis
Advantages
- Enables real‐time in vivo monitoring of cellular senescence using luciferase and red fluorescence reporters.
- Facilitates targeted investigation of distinct TGF‑β signaling pathways by eliminating canonical signaling through Smad3 knockout.
- Enhances the study of DNA damage responses by compromising homologous recombination repair in the Fancd2 knockout model.
- Provides a versatile platform for screening potential therapeutic agents that block or mitigate spike protein–induced pathologies.
- Improves the relevance of COVID-19 research by combining human ACE2 expression with specific genetic modifications.
IP Status
Research Tool
