Künzi, Lisa; Ryter, Sarah; Cornelius, Andreas; Leni, Zaira; Baumlin, Nathalie; Salathe, Matthias; Walser, Marcel; Engler, Olivier; Geiser, Marianne (2023). Transport of Designed Ankyrin Repeat Proteins through reconstituted human bronchial epithelia and protection against SARS-CoV-2. Scientific Reports, 13(1), p. 5537. Nature Publishing Group 10.1038/s41598-023-32269-1
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Clinical studies have proven antiviral effectiveness of treatment with a Designed Ankyrin Repeat Protein (DARPin) specific against the spike protein of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). More information on transport mechanisms and efficiency to the site of action is desirable. Transepithelial migration through air-liquid interface (ALI) cultures of reconstituted human bronchial epithelia (HBE) was assessed by Enzyme-Linked Immunosorbent Assays and Confocal Laser Scanning Microscopy for different DARPin designs in comparison to a monoclonal antibody. Antiviral efficacy against authentic SARS-CoV-2, applied apically on HBE, was investigated based on viral titers and genome equivalents, after administration of therapeutic candidates on the basal side. Transepithelial translocation of all DARPin candidates and the monoclonal antibody was efficient and dose dependent. Small DARPins and the antibody migrated more efficiently than larger molecules, indicating different transport mechanisms involved. Microscopic analyses support this, demonstrating passive paracellular transport of smaller DARPins and transcellular migration of the larger molecules. All therapeutic candidates applied to the basal side of HBE conferred effective protection against SARS-CoV-2 infection. In summary, we have shown that DARPins specific against SARS-CoV-2 translocate across intact airway epithelia and confer effective protection against infection and viral replication.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
09 Interdisciplinary Units > Microscopy Imaging Center (MIC) 04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy 04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Cell Biology |
UniBE Contributor: |
Künzi, Lisa, Leni, Zaira, Geiser, Marianne |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
2045-2322 |
Publisher: |
Nature Publishing Group |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
05 Apr 2023 13:55 |
Last Modified: |
15 Dec 2023 08:50 |
Publisher DOI: |
10.1038/s41598-023-32269-1 |
PubMed ID: |
37016030 |
BORIS DOI: |
10.48350/181526 |
URI: |
https://boris.unibe.ch/id/eprint/181526 |
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