A Lung-chip microphysiological system to model SARS-CoV-2 infection and test novel therapeutics

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Project Abstract SARS-CoV-2 novel coronavirus has caused a pandemic, presenting us with an urgent need to develop new models to study the pathophysiology of infection and test innovative therapeutics to combat disease. This proposal aims to use chip-based microphysiological systems to establish a model of the human lung to investigate SARS-CoV-2 infection and test novel antisense oligonucleotide (ASO) therapies to reduce viral entry and replication. Using human primary and induced pluripotent stem cell (iPSC)-derived lung epithelium, we will generate both proximal and distal airway chip models, infect with live SARS-CoV-2, and test newly designed ASOs to target host cell components to prevent viral entry and conserved viral sequences to prevent replication. We have assembled an expert team of lung biologists, virologists, and pharmaceutical industry partners to complement the iPSC and organ-chip technologies our lab has been developing over the past five years. We feel that the approach presented in this proposal will yield rapid results by generating human- relevant models to better understand the pathological mechanisms of SARS-CoV-2 infection and test novel therapeutic strategies currently in development by our pharmaceutical industry partner.