Primary human organoid models are an increasingly deployed platform for in vitro infectious disease modeling. The COVID-19 pandemic, engendered by the novel coronavirus SARS-CoV-2, represents a grave threat to public health and physiologic in vitro infection models are therefore urgently needed. This supplement request for U19AI116484, Stanford Cooperative Center for Novel, Alternative Model Systems for Enteric Diseases (Stanford NAMSED), requests funding to create new models for SARS-CoV-2 infection using novel human lung organoid technologies in collaboration with Dr. Ralph Baric at UNC, a recognized coronavirus authority. These studies exploit SARS-CoV-2 infection of organoids using a feeder-free, chemically defined human lung organoid system (Calvin Kuo lab), lung organoids with integrated immune components (Calvin Kuo), methods for robust apical-basal inversion of lung organoid polarity (Manuel Amieva), BSL3 single cell RNA-seq (Catherine Blish) and SARS-CoV-2-GFP indicator strains and BSL3 facilities (Ralph Baric). The SARS-CoV-2 infection of lung organoids will occur in BSL3 containment at both UNC and Stanford to compare apical versus basal infection routes, document how epithelial infection initiates secondary immune responses, and overall generate improved 3D physiological models of SARS-CoV-2-GFP infection relevant to therapeutics screening.

Public Health Relevance

The COVID-19 pandemic is caused by the novel coronavirus SARS-CoV-2 and new treatments and an improved understanding of viral biology are both urgently needed. Here, we have developed methods to grow human lung tissue in incubators as 3D mini-organs, termed ?organoids?, which will be infected with SARS-CoV-2 to allow the infection to be studied outside of the human body and to screen potential treatments.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Program--Cooperative Agreements (U19)
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Alarcon, Rodolfo M
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Stanford University
Internal Medicine/Medicine
Schools of Medicine
United States
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