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Status |
Public on Jan 13, 2024 |
Title |
Inhalation of ACE2-expressing lung spheroid cell exosomes provides prophylactic protection against SARS-CoV-2 |
Organism |
Mesocricetus auratus |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Continued emergence of SARS-CoV-2 variants of concern that are capable of escaping vaccine-induced immunity pose the urgency for developing new COVID-19 therapeutics. An essential mechanism for SARS-CoV-2 infection begins with the viral spike protein binding to the human ACE2. Consequently, inhibiting this interaction is a highly promising therapeutic strategy against COVID-19. Herein, we demonstrate that ACE2-expressing human lung spheroid cells (LSC)-derived exosomes (LSC-Exo) could function as a prophylactic agent to bind and neutralize SARS-CoV-2 and protect the host against SARS-CoV-2 infection. Inhalation of LSC-Exo facilitates their deposition and biodistribution throughout the whole lung in a female mouse model. We show that LSC-Exo blocks the interaction of SARS-CoV-2 with host cells in vitro and in vivo by neutralizing the virus. LSC-Exo treatment protected hamsters from SARS-CoV-2-induced disease and reduced viral loads. Furthermore, LSC-Exo intercept the entry of multiple SARS-CoV-2 variant pseudoviruses in female mice and show comparable or equal potency against the wild-type strain, demonstrating that LSC-Exo may act as broad-spectrum protectant against existing and emerging virus variants.
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Overall design |
To To elucidate the underlying protection mechanisms of LSC-Exo against SARS-CoV-2 infection, the bulk RNA sequencing (RNA-seq) analysis on lung tissues of infected hamsters that received PBS or LSC-Exo treatment was performed.
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Citation(s) |
38472181 |
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Submission date |
Dec 12, 2023 |
Last update date |
Mar 20, 2024 |
Contact name |
Zhenzhen Wang |
E-mail(s) |
zwang222@ncsu.edu
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Phone |
(571) 315-6096
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Organization name |
North Carolina State University
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Street address |
1060 William Moore Dr
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City |
Raleigh |
State/province |
North Carolina |
ZIP/Postal code |
27606-2600 |
Country |
USA |
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Platforms (1) |
GPL29254 |
Illumina HiSeq 4000 (Mesocricetus auratus) |
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Samples (8)
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Relations |
BioProject |
PRJNA1051566 |