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Long-acting nanoparticulate DNase-1 for effective suppression of SARS-CoV-2-mediated neutrophil activities and cytokine storm

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Title
Long-acting nanoparticulate DNase-1 for effective suppression of SARS-CoV-2-mediated neutrophil activities and cytokine storm
Author(s)
Yun Young Lee; Hee Ho Park; Wooram Park; Hyelim Kim; Jong Geol Jang; Kyung Soo Hong; Jae-Young Lee; Hee Seung Seo; Dong Hee Na; Tae-Hyung Kim; Young Bin Choy; June Hong Ahn; Wonhwa Lee; Chun Gwon Park
Subject
EXTRACELLULAR TRAPS, ; SEPSIS, ; SURVIVAL, ; DEATH
Publication Date
2021-01
Journal
BIOMATERIALS, v.267, pp.120389
Publisher
ELSEVIER SCI LTD
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a new strain of coronavirus not previously identified in humans. Globally, the number of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) have risen dramatically. Currently, there are no FDA-approved antiviral drugs and there is an urgency to develop treatment strategies that can effectively suppress SARS-CoV-2-mediated cytokine storms, acute respiratory distress syndrome (ARDS), and sepsis. As symptoms progress in patients with SARS-CoV-2 sepsis, elevated amounts of cell-free DNA (cfDNA) are produced, which in turn induce multiple organ failure in these patients. Furthermore, plasma levels of DNase-1 are markedly reduced in SARS-CoV-2 sepsis patients. In this study, we generated recombinant DNase-1-coated polydopamine-poly(ethylene glycol) nanoparticulates (named long-acting DNase-1), and hypothesized that exogenous administration of long-acting DNase-1 may suppress SARS-CoV-2-mediated neutrophil activities and the cytokine storm. Our findings suggest that exogenously administered long-acting nanoparticulate DNase-1 can effectively reduce cfDNA levels and neutrophil activities and may be used as a potential therapeutic intervention for life-threatening SARS-CoV-2-mediated illnesses.
URI
https://pr.ibs.re.kr/handle/8788114/8425
DOI
10.1016/j.biomaterials.2020.120389
ISSN
0142-9612
Appears in Collections:
Center for Neuroscience Imaging Research (뇌과학 이미징 연구단) > 1. Journal Papers (저널논문)
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