A High-Throughput, High-Containment Human Primary Epithelial Airway Organ-on-Chip Platform for SARS-CoV-2 Therapeutic Screening.

Autor: Fisher CR; Bioengineering Division, Draper, Cambridge, MA 02139, USA., Mba Medie F; Bioengineering Division, Draper, Cambridge, MA 02139, USA., Luu RJ; Bioengineering Division, Draper, Cambridge, MA 02139, USA., Gaibler RB; Bioengineering Division, Draper, Cambridge, MA 02139, USA., Mulhern TJ; Bioengineering Division, Draper, Cambridge, MA 02139, USA., Miller CR; Bioengineering Division, Draper, Cambridge, MA 02139, USA., Zhang CJ; Bioengineering Division, Draper, Cambridge, MA 02139, USA., Rubio LD; Bioengineering Division, Draper, Cambridge, MA 02139, USA., Marr EE; Bioengineering Division, Draper, Cambridge, MA 02139, USA., Vijayakumar V; Bioengineering Division, Draper, Cambridge, MA 02139, USA., Gabriel EP; Bioengineering Division, Draper, Cambridge, MA 02139, USA., Lopez Quezada L; Bioengineering Division, Draper, Cambridge, MA 02139, USA., Zhang CH; Department of Chemistry, Yale University, New Haven, CT 06520, USA., Anderson KS; Department of Pharmacology, Yale University, New Haven, CT 06520, USA.; Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA., Jorgensen WL; Department of Chemistry, Yale University, New Haven, CT 06520, USA., Alladina JW; Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA 02114, USA., Medoff BD; Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, MA 02114, USA., Borenstein JT; Bioengineering Division, Draper, Cambridge, MA 02139, USA., Gard AL; Bioengineering Division, Draper, Cambridge, MA 02139, USA.
Jazyk: angličtina
Zdroj: Cells [Cells] 2023 Nov 16; Vol. 12 (22). Date of Electronic Publication: 2023 Nov 16.
DOI: 10.3390/cells12222639
Abstrakt: COVID-19 emerged as a worldwide pandemic in early 2020, and while the rapid development of safe and efficacious vaccines stands as an extraordinary achievement, the identification of effective therapeutics has been less successful. This process has been limited in part by a lack of human-relevant preclinical models compatible with therapeutic screening on the native virus, which requires a high-containment environment. Here, we report SARS-CoV-2 infection and robust viral replication in PREDICT96-ALI, a high-throughput, human primary cell-based organ-on-chip platform. We evaluate unique infection kinetic profiles across lung tissue from three human donors by immunofluorescence, RT-qPCR, and plaque assays over a 6-day infection period. Enabled by the 96 devices/plate throughput of PREDICT96-ALI, we also investigate the efficacy of Remdesivir and MPro61 in a proof-of-concept antiviral study. Both compounds exhibit an antiviral effect against SARS-CoV-2 in the platform. This demonstration of SARS-CoV-2 infection and antiviral dosing in a high-throughput organ-on-chip platform presents a critical capability for disease modeling and therapeutic screening applications in a human physiology-relevant in vitro system.
Databáze: MEDLINE
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