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

Project AbstractSARS-CoV-2 novel coronavirus has caused a pandemic, presenting us with an urgent need to develop newmodels to study the pathophysiology of infection and test innovative therapeutics to combat disease. Thisproposal aims to use chip-based microphysiological systems to establish a model of the human lung toinvestigate SARS-CoV-2 infection and test novel antisense oligonucleotide (ASO) therapies to reduce viralentry 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 newlydesigned ASOs to target host cell components to prevent viral entry and conserved viral sequences to preventreplication. We have assembled an expert team of lung biologists, virologists, and pharmaceutical industrypartners to complement the iPSC and organ-chip technologies our lab has been developing over the past fiveyears. 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 noveltherapeutic strategies currently in development by our pharmaceutical industry partner.