| RRC ID |
86028
|
| Author |
Nakagawa Y, Kawaguchi Y, Hirose H, Hashiguchi T, Lee J, Hotta A, Kawamoto J, Sasaki M, Sawa H, Futaki S.
|
| Title |
SARS-CoV-2 inhibition through mRNA delivery using engineered extracellular vesicles displaying the spike protein.
|
| Journal |
Biomaterials
|
| Abstract |
Coronavirus disease (COVID-19) caused by severe acute respiratory coronavirus 2 (SARS-CoV-2), has been the biggest pandemic in recent years, and there is a growing demand for the development of new modalities to treat emerging infections rapidly. Extracellular vesicles (EVs) are promising new biocompatible drug carriers; however, their specificity and delivery efficiency remain challenging. In this study, we aimed to develop EVs displaying the SARS-CoV-2 Spike (S) protein as a new modality to inhibit SARS-CoV-2 infection. The S protein-displaying EVs which were the pellet fractions of centrifugation at 10,000×g (S-EVs10K) were found to selectively bind to cells expressing angiotensin-converting enzyme 2 (ACE2). Cleavage of the S protein using proteases such as transmembrane serine protease 2 (TMPRSS2) and cathepsins led to successful membrane fusion of the EVs10K with the target cell. Experiments using viral infection inhibitors in TMPRSS2-expressing Vero E6 cells further confirmed the membrane fusion of S-EVs10K in an ACE2-and TMPRSS2-dependent manner. Additionally, we demonstrated the potential of S-EVs10K as novel mRNA carriers to inhibit SARS-CoV-2 infection by encapsulating the mRNA encoding HAI-2, a TMPRSS2-inhibiting membrane protein. Marked suppression of SARS-CoV-2 entry into TMPRSS2-expressing Vero E6 cells was confirmed using pseudotyped virus-like particles. These findings suggest the potential of S-EVs10K for selective mRNA delivery to target cells via membrane fusion, serving as a new modality for inhibiting SARS-CoV-2 infection by delivering mRNA encoding inhibitory proteins.
|
| Volume |
325
|
| Pages |
123594
|
| Published |
2026-2-1
|
| DOI |
10.1016/j.biomaterials.2025.123594
|
| PII |
S0142-9612(25)00513-7
|
| PMID |
40763580
|
| MeSH |
Angiotensin-Converting Enzyme 2 / metabolism
Animals
COVID-19 / virology
COVID-19 Drug Treatment
Chlorocebus aethiops
Extracellular Vesicles* / chemistry
Extracellular Vesicles* / metabolism
Humans
RNA, Messenger* / administration & dosage
RNA, Messenger* / genetics
RNA, Messenger* / metabolism
SARS-CoV-2* / drug effects
SARS-CoV-2* / genetics
SARS-CoV-2* / physiology
Serine Endopeptidases / metabolism
Spike Glycoprotein, Coronavirus* / genetics
Spike Glycoprotein, Coronavirus* / metabolism
Vero Cells
|
| IF |
10.317
|
| Resource |
| Human and Animal Cells |
293T(RCB2202) |
| DNA material |
CSII-CMV-MCS-IRES2-Bsd (RDB04385) |
