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

NIH Pandemic-Era Grants

Pandemic Era Grants

2020

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Principal Investigator: CLIVE Niels SVENDSEN
Organization: CEDARS-SINAI MEDICAL CENTER
Fiscal Year: 2020
Award: $1,163,750
Funding agency: National Institute of Neurological Disorders and Stroke

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.

Terms: <2019 novel coronavirus><2019-nCoV><ASO therapeutics><ASO therapy><ASO treatment><Aerosols><Air><Alveolar><Amyotrophic Lateral Sclerosis><Amyotrophic Lateral Sclerosis Motor Neuron Disease><Anti-Sense Oligonucleotides><Anti-sense Technology><Antisense Agent><Antisense Oligonucleotide Therapy><Antisense Oligonucleotides><Antisense Technology><Antiviral Agents><Antiviral Drugs><Antivirals><Award><BSL-3 facility><BSL3 facility><Blood - brain barrier anatomy><Blood-Brain Barrier><Body Tissues><Brain><Brain Nervous System><CF patients><COVID><COVID-19><COVID-19 epidemic><COVID-19 pandemic><COVID19><COVID19 epidemic><COVID19 pandemic><Cardiac Muscle Cells><Cardiac Myocytes><Cardiocyte><Cell Body><Cell Components><Cell Line><Cell Structure><CellLine><Cells><Cellular Structures><Clinical Trials><CoV disease><CoV emergence><Collaborations><Complement><Complement Proteins><Complex><Cystic Fibrosis><Data><Development><Disease><Disorder><Distal><Drug Industry><Drug resistant viral><Drugs><Dysfunction><Encephalon><Endoderm><Epithelial><Epithelial Cells><Epitheliasin Gene><Epithelium><Epithelium Part><Esteroproteases><Functional disorder><Future><Gehrig's Disease><Gene Expression><Genome><Heart Muscle Cells><Heart myocyte><Hemato-Encephalic Barrier><Human><In Vitro><Infection><Institute of Medicine><Institute of Medicine (U.S.)><Investigators><Liquid substance><Lou Gehrig Disease><Lung><Lung Alveolar Epithelia><Lung Respiratory System><Medical><Medication><Medulla Spinalis><Methods><Modeling><Modern Man><Mucoviscidosis><NAS/IOM><NIH><National Institutes of Health><Organ><Organoids><PRSS10><Paralysis Agitans><Parents><Parkinson><Parkinson Disease><Parkinson's disease><Parkinsons disease><Pathologic><Patients><Peptidases><Peptide Hydrolases><Pharmaceutic Industry><Pharmaceutic Preparations><Pharmaceutical Agent><Pharmaceutical Industry><Pharmaceutical Preparations><Pharmaceuticals><Pharmacologic Substance><Pharmacological Substance><Phase><Physiology><Physiopathology><Plant Embryos><Plant Zygotes><Primary Parkinsonism><Property><Protease Gene><Proteases><Proteinases><Proteins><Proteolytic Enzymes><Protocol><Protocols documentation><Receptor Protein><Regenerative Medicine><Research Personnel><Research Resources><Researchers><Resources><SARS-CoV-2><SARS-CoV2><SARS-associated coronavirus 2><SARS-coronavirus-2><SARS-related coronavirus 2><Sampling><Seeds><Severe acute respiratory syndrome coronavirus 2><Side><Source><Spanish flu><Spanish influenza><Spinal Cord><Strains Cell Lines><System><TMPRSS2><TMPRSS2 gene><Techniques><Technology><Testing><Therapeutic><Time><Tissues><Transcript><United States National Institutes of Health><Vaccines><Validation><Viral><Viral Genes><Viral Receptor><Virus><Virus Receptors><Work><Wuhan coronavirus><airway epithelium><alveolar epithelium><anti-sense agent><anti-sense oligo><anti-sense oligonucleotide therapy><anti-sense therapy><anti-viral agents><anti-viral drugs><anti-virals><antisense oligo><antisense therapy><base><biosafety level 3 facility><bloodbrain barrier><cardiomyocyte><cell type><clinical development><clinical relevance><clinically relevant><combat><corona virus disease><corona virus disease 2019><corona virus disease 2019 epidemic><corona virus disease 2019 pandemic><coronavirus disease><coronavirus disease 2019><coronavirus disease 2019 epidemic><coronavirus disease 2019 pandemic><coronavirus emergence><cultured cell line><cystic fibrosis patients><design><designing><develop therapy><developmental><drug efficacy><drug resistant virus><drug/agent><emergent CoV><emergent coronavirus><emerging CoV><emerging coronavirus><epithelial progenitor cell><epithelial stem cell><experiment><experimental research><experimental study><fluid><human disease><iPS><iPSC><iPSCs><in vitro Model><individuals with CF><individuals with cystic fibrosis><induced pluripotent stem cell><industrial partnership><industry partner><industry partnership><infection rate><innovate><innovation><innovative><intervention development><liquid><lung basal segment><lung base><microphysiologic model><microphysiologic platform><microphysiologic system><microphysiology model><microphysiology platform><microphysiology system><nCoV><new CoV><new approaches><new coronavirus><new drug treatments><new drugs><new therapeutics><new therapy><next generation therapeutics><novel><novel CoV><novel approaches><novel coronavirus><novel drug treatments><novel drugs><novel strategies><novel strategy><novel therapeutics><novel therapy><open source><pandemic><pandemic disease><pathophysiology><patients with CF><patients with cystic fibrosis><prevent><preventing><pulmonary><rate of infection><receptor><respiratory><seed><small molecule><therapy development><treatment development><viral RNA><viral genomics><virus RNA><virus genomics>