A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics.
Identifieur interne : 000771 ( Main/Exploration ); précédent : 000770; suivant : 000772A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics.
Auteurs : Longlong Si [États-Unis] ; Haiqing Bai [États-Unis] ; Melissa Rodas [États-Unis] ; Wuji Cao [États-Unis] ; Crystal Yuri Oh [États-Unis] ; Amanda Jiang [États-Unis] ; Rasmus Moller [États-Unis] ; Daisy Hoagland [États-Unis] ; Kohei Oishi [États-Unis] ; Shu Horiuchi [États-Unis] ; Skyler Uhl [États-Unis] ; Daniel Blanco-Melo [États-Unis] ; Randy A. Albrecht [États-Unis] ; Wen-Chun Liu [États-Unis] ; Tristan Jordan [États-Unis] ; Benjamin E. Nilsson-Payant [États-Unis] ; Ilona Golynker [États-Unis] ; Justin Frere [États-Unis] ; James Logue [États-Unis] ; Robert Haupt [États-Unis] ; Marisa Mcgrath [États-Unis] ; Stuart Weston [États-Unis] ; Tian Zhang [États-Unis] ; Roberto Plebani [États-Unis, Italie] ; Mercy Soong [États-Unis] ; Atiq Nurani [États-Unis] ; Seong Min Kim [États-Unis] ; Danni Y. Zhu [États-Unis] ; Kambez H. Benam [États-Unis] ; Girija Goyal [États-Unis] ; Sarah E. Gilpin [États-Unis] ; Rachelle Prantil-Baun [États-Unis] ; Steven P. Gygi [États-Unis] ; Rani K. Powers [États-Unis] ; Kenneth E. Carlson [États-Unis] ; Matthew Frieman [États-Unis] ; Benjamin R. Tenoever [États-Unis] ; Donald E. Ingber [États-Unis]Source :
- Nature biomedical engineering [ 2157-846X ] ; 2021.
Abstract
The rapid repurposing of antivirals is particularly pressing during pandemics. However, rapid assays for assessing candidate drugs typically involve in vitro screens and cell lines that do not recapitulate human physiology at the tissue and organ levels. Here we show that a microfluidic bronchial-airway-on-a-chip lined by highly differentiated human bronchial-airway epithelium and pulmonary endothelium can model viral infection, strain-dependent virulence, cytokine production and the recruitment of circulating immune cells. In airway chips infected with influenza A, the co-administration of nafamostat with oseltamivir doubled the treatment-time window for oseltamivir. In chips infected with pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinically relevant doses of the antimalarial drug amodiaquine inhibited infection but clinical doses of hydroxychloroquine and other antiviral drugs that inhibit the entry of pseudotyped SARS-CoV-2 in cell lines under static conditions did not. We also show that amodiaquine showed substantial prophylactic and therapeutic activities in hamsters challenged with native SARS-CoV-2. The human airway-on-a-chip may accelerate the identification of therapeutics and prophylactics with repurposing potential.
DOI: 10.1038/s41551-021-00718-9
PubMed: 33941899
Affiliations:
- Italie, États-Unis
- Maryland, Massachusetts, Pennsylvanie, État de New York
- Cambridge (Massachusetts), Pittsburgh
- Université Harvard, Université de Pittsburgh
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(CAST), Department of Medical, Oral and Biotechnological Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Center on Advanced Studies and Technology (CAST), Department of Medical, Oral and Biotechnological Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti</wicri:regionArea><wicri:noRegion>Chieti</wicri:noRegion></affiliation></author><author><name sortKey="Soong, Mercy" sort="Soong, Mercy" uniqKey="Soong M" first="Mercy" last="Soong">Mercy Soong</name><affiliation wicri:level="4"><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Nurani, Atiq" sort="Nurani, Atiq" uniqKey="Nurani A" first="Atiq" last="Nurani">Atiq Nurani</name><affiliation wicri:level="4"><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Kim, Seong Min" sort="Kim, Seong Min" uniqKey="Kim S" first="Seong Min" last="Kim">Seong Min Kim</name><affiliation wicri:level="4"><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Zhu, Danni Y" sort="Zhu, Danni Y" uniqKey="Zhu D" first="Danni Y" last="Zhu">Danni Y. Zhu</name><affiliation wicri:level="4"><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Benam, Kambez H" sort="Benam, Kambez H" uniqKey="Benam K" first="Kambez H" last="Benam">Kambez H. 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Gygi</name><affiliation wicri:level="2"><nlm:affiliation>Department of Cell Biology, Harvard Medical School, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Cell Biology, Harvard Medical School, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Powers, Rani K" sort="Powers, Rani K" uniqKey="Powers R" first="Rani K" last="Powers">Rani K. 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Carlson</name><affiliation wicri:level="4"><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Frieman, Matthew" sort="Frieman, Matthew" uniqKey="Frieman M" first="Matthew" last="Frieman">Matthew Frieman</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Tenoever, Benjamin R" sort="Tenoever, Benjamin R" uniqKey="Tenoever B" first="Benjamin R" last="Tenoever">Benjamin R. Tenoever</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Ingber, Donald E" sort="Ingber, Donald E" uniqKey="Ingber D" first="Donald E" last="Ingber">Donald E. Ingber</name><affiliation wicri:level="4"><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. don.ingber@wyss.harvard.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. don.ingber@wyss.harvard.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA, USA. don.ingber@wyss.harvard.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2021">2021</date><idno type="RBID">pubmed:33941899</idno><idno type="pmid">33941899</idno><idno type="doi">10.1038/s41551-021-00718-9</idno><idno type="wicri:Area/Main/Corpus">000057</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Corpus" wicri:corpus="PubMed">000057</idno><idno type="wicri:Area/Main/Curation">000057</idno><idno type="wicri:explorRef" wicri:stream="Main" wicri:step="Curation">000057</idno><idno type="wicri:Area/Main/Exploration">000057</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en">A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics.</title><author><name sortKey="Si, Longlong" sort="Si, Longlong" uniqKey="Si L" first="Longlong" last="Si">Longlong Si</name><affiliation wicri:level="4"><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Bai, Haiqing" sort="Bai, Haiqing" uniqKey="Bai H" first="Haiqing" last="Bai">Haiqing Bai</name><affiliation wicri:level="4"><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Rodas, Melissa" sort="Rodas, Melissa" uniqKey="Rodas M" first="Melissa" last="Rodas">Melissa Rodas</name><affiliation wicri:level="4"><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Cao, Wuji" sort="Cao, Wuji" uniqKey="Cao W" first="Wuji" last="Cao">Wuji Cao</name><affiliation wicri:level="4"><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Oh, Crystal Yuri" sort="Oh, Crystal Yuri" uniqKey="Oh C" first="Crystal Yuri" last="Oh">Crystal Yuri Oh</name><affiliation wicri:level="4"><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Jiang, Amanda" sort="Jiang, Amanda" uniqKey="Jiang A" first="Amanda" last="Jiang">Amanda Jiang</name><affiliation wicri:level="4"><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Moller, Rasmus" sort="Moller, Rasmus" uniqKey="Moller R" first="Rasmus" last="Moller">Rasmus Moller</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Hoagland, Daisy" sort="Hoagland, Daisy" uniqKey="Hoagland D" first="Daisy" last="Hoagland">Daisy Hoagland</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Oishi, Kohei" sort="Oishi, Kohei" uniqKey="Oishi K" first="Kohei" last="Oishi">Kohei Oishi</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Horiuchi, Shu" sort="Horiuchi, Shu" uniqKey="Horiuchi S" first="Shu" last="Horiuchi">Shu Horiuchi</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Uhl, Skyler" sort="Uhl, Skyler" uniqKey="Uhl S" first="Skyler" last="Uhl">Skyler Uhl</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Blanco Melo, Daniel" sort="Blanco Melo, Daniel" uniqKey="Blanco Melo D" first="Daniel" last="Blanco-Melo">Daniel Blanco-Melo</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Albrecht, Randy A" sort="Albrecht, Randy A" uniqKey="Albrecht R" first="Randy A" last="Albrecht">Randy A. Albrecht</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Liu, Wen Chun" sort="Liu, Wen Chun" uniqKey="Liu W" first="Wen-Chun" last="Liu">Wen-Chun Liu</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Jordan, Tristan" sort="Jordan, Tristan" uniqKey="Jordan T" first="Tristan" last="Jordan">Tristan Jordan</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Nilsson Payant, Benjamin E" sort="Nilsson Payant, Benjamin E" uniqKey="Nilsson Payant B" first="Benjamin E" last="Nilsson-Payant">Benjamin E. Nilsson-Payant</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Golynker, Ilona" sort="Golynker, Ilona" uniqKey="Golynker I" first="Ilona" last="Golynker">Ilona Golynker</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Frere, Justin" sort="Frere, Justin" uniqKey="Frere J" first="Justin" last="Frere">Justin Frere</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Logue, James" sort="Logue, James" uniqKey="Logue J" first="James" last="Logue">James Logue</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Haupt, Robert" sort="Haupt, Robert" uniqKey="Haupt R" first="Robert" last="Haupt">Robert Haupt</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Mcgrath, Marisa" sort="Mcgrath, Marisa" uniqKey="Mcgrath M" first="Marisa" last="Mcgrath">Marisa Mcgrath</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Weston, Stuart" sort="Weston, Stuart" uniqKey="Weston S" first="Stuart" last="Weston">Stuart Weston</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Zhang, Tian" sort="Zhang, Tian" uniqKey="Zhang T" first="Tian" last="Zhang">Tian Zhang</name><affiliation wicri:level="2"><nlm:affiliation>Department of Cell Biology, Harvard Medical School, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Cell Biology, Harvard Medical School, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Plebani, Roberto" sort="Plebani, Roberto" uniqKey="Plebani R" first="Roberto" last="Plebani">Roberto Plebani</name><affiliation wicri:level="4"><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation><affiliation wicri:level="1"><nlm:affiliation>Center on Advanced Studies and Technology (CAST), Department of Medical, Oral and Biotechnological Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy.</nlm:affiliation><country xml:lang="fr">Italie</country><wicri:regionArea>Center on Advanced Studies and Technology (CAST), Department of Medical, Oral and Biotechnological Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti</wicri:regionArea><wicri:noRegion>Chieti</wicri:noRegion></affiliation></author><author><name sortKey="Soong, Mercy" sort="Soong, Mercy" uniqKey="Soong M" first="Mercy" last="Soong">Mercy Soong</name><affiliation wicri:level="4"><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Nurani, Atiq" sort="Nurani, Atiq" uniqKey="Nurani A" first="Atiq" last="Nurani">Atiq Nurani</name><affiliation wicri:level="4"><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Kim, Seong Min" sort="Kim, Seong Min" uniqKey="Kim S" first="Seong Min" last="Kim">Seong Min Kim</name><affiliation wicri:level="4"><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Zhu, Danni Y" sort="Zhu, Danni Y" uniqKey="Zhu D" first="Danni Y" last="Zhu">Danni Y. Zhu</name><affiliation wicri:level="4"><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Benam, Kambez H" sort="Benam, Kambez H" uniqKey="Benam K" first="Kambez H" last="Benam">Kambez H. Benam</name><affiliation wicri:level="4"><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation><affiliation wicri:level="4"><nlm:affiliation>Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region><settlement type="city">Pittsburgh</settlement></placeName><orgName type="university">Université de Pittsburgh</orgName></affiliation></author><author><name sortKey="Goyal, Girija" sort="Goyal, Girija" uniqKey="Goyal G" first="Girija" last="Goyal">Girija Goyal</name><affiliation wicri:level="4"><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Gilpin, Sarah E" sort="Gilpin, Sarah E" uniqKey="Gilpin S" first="Sarah E" last="Gilpin">Sarah E. Gilpin</name><affiliation wicri:level="4"><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Prantil Baun, Rachelle" sort="Prantil Baun, Rachelle" uniqKey="Prantil Baun R" first="Rachelle" last="Prantil-Baun">Rachelle Prantil-Baun</name><affiliation wicri:level="4"><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Gygi, Steven P" sort="Gygi, Steven P" uniqKey="Gygi S" first="Steven P" last="Gygi">Steven P. Gygi</name><affiliation wicri:level="2"><nlm:affiliation>Department of Cell Biology, Harvard Medical School, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Cell Biology, Harvard Medical School, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author><author><name sortKey="Powers, Rani K" sort="Powers, Rani K" uniqKey="Powers R" first="Rani K" last="Powers">Rani K. Powers</name><affiliation wicri:level="4"><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Carlson, Kenneth E" sort="Carlson, Kenneth E" uniqKey="Carlson K" first="Kenneth E" last="Carlson">Kenneth E. Carlson</name><affiliation wicri:level="4"><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation></author><author><name sortKey="Frieman, Matthew" sort="Frieman, Matthew" uniqKey="Frieman M" first="Matthew" last="Frieman">Matthew Frieman</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD</wicri:regionArea><placeName><region type="state">Maryland</region></placeName></affiliation></author><author><name sortKey="Tenoever, Benjamin R" sort="Tenoever, Benjamin R" uniqKey="Tenoever B" first="Benjamin R" last="Tenoever">Benjamin R. Tenoever</name><affiliation wicri:level="2"><nlm:affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY</wicri:regionArea><placeName><region type="state">État de New York</region></placeName></affiliation></author><author><name sortKey="Ingber, Donald E" sort="Ingber, Donald E" uniqKey="Ingber D" first="Donald E" last="Ingber">Donald E. Ingber</name><affiliation wicri:level="4"><nlm:affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. don.ingber@wyss.harvard.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region><settlement type="city">Cambridge (Massachusetts)</settlement></placeName><orgName type="university">Université Harvard</orgName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. don.ingber@wyss.harvard.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation><affiliation wicri:level="2"><nlm:affiliation>Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA, USA. don.ingber@wyss.harvard.edu.</nlm:affiliation><country xml:lang="fr">États-Unis</country><wicri:regionArea>Harvard John A. Paulson School of Engineering and Applied Sciences, Cambridge, MA</wicri:regionArea><placeName><region type="state">Massachusetts</region></placeName></affiliation></author></analytic><series><title level="j">Nature biomedical engineering</title><idno type="eISSN">2157-846X</idno><imprint><date when="2021" type="published">2021</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">The rapid repurposing of antivirals is particularly pressing during pandemics. However, rapid assays for assessing candidate drugs typically involve in vitro screens and cell lines that do not recapitulate human physiology at the tissue and organ levels. Here we show that a microfluidic bronchial-airway-on-a-chip lined by highly differentiated human bronchial-airway epithelium and pulmonary endothelium can model viral infection, strain-dependent virulence, cytokine production and the recruitment of circulating immune cells. In airway chips infected with influenza A, the co-administration of nafamostat with oseltamivir doubled the treatment-time window for oseltamivir. In chips infected with pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinically relevant doses of the antimalarial drug amodiaquine inhibited infection but clinical doses of hydroxychloroquine and other antiviral drugs that inhibit the entry of pseudotyped SARS-CoV-2 in cell lines under static conditions did not. We also show that amodiaquine showed substantial prophylactic and therapeutic activities in hamsters challenged with native SARS-CoV-2. The human airway-on-a-chip may accelerate the identification of therapeutics and prophylactics with repurposing potential.</div></front></TEI><pubmed><MedlineCitation Status="Publisher" Owner="NLM"><PMID Version="1">33941899</PMID><DateRevised><Year>2021</Year><Month>05</Month><Day>04</Day></DateRevised><Article PubModel="Print-Electronic"><Journal><ISSN IssnType="Electronic">2157-846X</ISSN><JournalIssue CitedMedium="Internet"><PubDate><Year>2021</Year><Month>May</Month><Day>03</Day></PubDate></JournalIssue><Title>Nature biomedical engineering</Title><ISOAbbreviation>Nat Biomed Eng</ISOAbbreviation></Journal><ArticleTitle>A human-airway-on-a-chip for the rapid identification of candidate antiviral therapeutics and prophylactics.</ArticleTitle><ELocationID EIdType="doi" ValidYN="Y">10.1038/s41551-021-00718-9</ELocationID><Abstract><AbstractText>The rapid repurposing of antivirals is particularly pressing during pandemics. However, rapid assays for assessing candidate drugs typically involve in vitro screens and cell lines that do not recapitulate human physiology at the tissue and organ levels. Here we show that a microfluidic bronchial-airway-on-a-chip lined by highly differentiated human bronchial-airway epithelium and pulmonary endothelium can model viral infection, strain-dependent virulence, cytokine production and the recruitment of circulating immune cells. In airway chips infected with influenza A, the co-administration of nafamostat with oseltamivir doubled the treatment-time window for oseltamivir. In chips infected with pseudotyped severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), clinically relevant doses of the antimalarial drug amodiaquine inhibited infection but clinical doses of hydroxychloroquine and other antiviral drugs that inhibit the entry of pseudotyped SARS-CoV-2 in cell lines under static conditions did not. We also show that amodiaquine showed substantial prophylactic and therapeutic activities in hamsters challenged with native SARS-CoV-2. The human airway-on-a-chip may accelerate the identification of therapeutics and prophylactics with repurposing potential.</AbstractText></Abstract><AuthorList CompleteYN="Y"><Author ValidYN="Y" EqualContrib="Y"><LastName>Si</LastName><ForeName>Longlong</ForeName><Initials>L</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-0504-1659</Identifier><AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y" EqualContrib="Y"><LastName>Bai</LastName><ForeName>Haiqing</ForeName><Initials>H</Initials><AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Rodas</LastName><ForeName>Melissa</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Cao</LastName><ForeName>Wuji</ForeName><Initials>W</Initials><AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Oh</LastName><ForeName>Crystal Yuri</ForeName><Initials>CY</Initials><AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jiang</LastName><ForeName>Amanda</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Moller</LastName><ForeName>Rasmus</ForeName><Initials>R</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-8452-0761</Identifier><AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Hoagland</LastName><ForeName>Daisy</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Oishi</LastName><ForeName>Kohei</ForeName><Initials>K</Initials><AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Horiuchi</LastName><ForeName>Shu</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Uhl</LastName><ForeName>Skyler</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Blanco-Melo</LastName><ForeName>Daniel</ForeName><Initials>D</Initials><AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Albrecht</LastName><ForeName>Randy A</ForeName><Initials>RA</Initials><Identifier Source="ORCID">http://orcid.org/0000-0003-4008-503X</Identifier><AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Liu</LastName><ForeName>Wen-Chun</ForeName><Initials>WC</Initials><AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Jordan</LastName><ForeName>Tristan</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nilsson-Payant</LastName><ForeName>Benjamin E</ForeName><Initials>BE</Initials><Identifier Source="ORCID">http://orcid.org/0000-0003-2661-7837</Identifier><AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Golynker</LastName><ForeName>Ilona</ForeName><Initials>I</Initials><AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Frere</LastName><ForeName>Justin</ForeName><Initials>J</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-7514-8873</Identifier><AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Logue</LastName><ForeName>James</ForeName><Initials>J</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-7410-9741</Identifier><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Haupt</LastName><ForeName>Robert</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>McGrath</LastName><ForeName>Marisa</ForeName><Initials>M</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-7451-4958</Identifier><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Weston</LastName><ForeName>Stuart</ForeName><Initials>S</Initials><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhang</LastName><ForeName>Tian</ForeName><Initials>T</Initials><AffiliationInfo><Affiliation>Department of Cell Biology, Harvard Medical School, Boston, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Plebani</LastName><ForeName>Roberto</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Center on Advanced Studies and Technology (CAST), Department of Medical, Oral and Biotechnological Sciences, "G. d'Annunzio" University of Chieti-Pescara, Chieti, Italy.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Soong</LastName><ForeName>Mercy</ForeName><Initials>M</Initials><AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Nurani</LastName><ForeName>Atiq</ForeName><Initials>A</Initials><AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Kim</LastName><ForeName>Seong Min</ForeName><Initials>SM</Initials><AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Zhu</LastName><ForeName>Danni Y</ForeName><Initials>DY</Initials><AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Benam</LastName><ForeName>Kambez H</ForeName><Initials>KH</Initials><AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, University of Pittsburgh, Pittsburgh, PA, USA.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Goyal</LastName><ForeName>Girija</ForeName><Initials>G</Initials><AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gilpin</LastName><ForeName>Sarah E</ForeName><Initials>SE</Initials><AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Prantil-Baun</LastName><ForeName>Rachelle</ForeName><Initials>R</Initials><AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Gygi</LastName><ForeName>Steven P</ForeName><Initials>SP</Initials><Identifier Source="ORCID">http://orcid.org/0000-0001-7626-0034</Identifier><AffiliationInfo><Affiliation>Department of Cell Biology, Harvard Medical School, Boston, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Powers</LastName><ForeName>Rani K</ForeName><Initials>RK</Initials><AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Carlson</LastName><ForeName>Kenneth E</ForeName><Initials>KE</Initials><AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Frieman</LastName><ForeName>Matthew</ForeName><Initials>M</Initials><Identifier Source="ORCID">http://orcid.org/0000-0003-0107-0775</Identifier><AffiliationInfo><Affiliation>Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>tenOever</LastName><ForeName>Benjamin R</ForeName><Initials>BR</Initials><Identifier Source="ORCID">http://orcid.org/0000-0003-0324-3078</Identifier><AffiliationInfo><Affiliation>Department of Microbiology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.</Affiliation></AffiliationInfo></Author><Author ValidYN="Y"><LastName>Ingber</LastName><ForeName>Donald E</ForeName><Initials>DE</Initials><Identifier Source="ORCID">http://orcid.org/0000-0002-4319-6520</Identifier><AffiliationInfo><Affiliation>Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA, USA. don.ingber@wyss.harvard.edu.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Vascular Biology Program and Department of Surgery, Boston Children's Hospital and Harvard Medical School, Boston, MA, USA. don.ingber@wyss.harvard.edu.</Affiliation></AffiliationInfo><AffiliationInfo><Affiliation>Harvard John A. 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Powers</name><name sortKey="Prantil Baun, Rachelle" sort="Prantil Baun, Rachelle" uniqKey="Prantil Baun R" first="Rachelle" last="Prantil-Baun">Rachelle Prantil-Baun</name><name sortKey="Rodas, Melissa" sort="Rodas, Melissa" uniqKey="Rodas M" first="Melissa" last="Rodas">Melissa Rodas</name><name sortKey="Soong, Mercy" sort="Soong, Mercy" uniqKey="Soong M" first="Mercy" last="Soong">Mercy Soong</name><name sortKey="Tenoever, Benjamin R" sort="Tenoever, Benjamin R" uniqKey="Tenoever B" first="Benjamin R" last="Tenoever">Benjamin R. Tenoever</name><name sortKey="Uhl, Skyler" sort="Uhl, Skyler" uniqKey="Uhl S" first="Skyler" last="Uhl">Skyler Uhl</name><name sortKey="Weston, Stuart" sort="Weston, Stuart" uniqKey="Weston S" first="Stuart" last="Weston">Stuart Weston</name><name sortKey="Zhang, Tian" sort="Zhang, Tian" uniqKey="Zhang T" first="Tian" last="Zhang">Tian Zhang</name><name sortKey="Zhu, Danni Y" sort="Zhu, Danni Y" uniqKey="Zhu D" first="Danni Y" last="Zhu">Danni Y. Zhu</name></country><country name="Italie"><noRegion><name sortKey="Plebani, Roberto" sort="Plebani, Roberto" uniqKey="Plebani R" first="Roberto" last="Plebani">Roberto Plebani</name></noRegion></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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