한빛사 논문
Yun Young Leea,1, Hee Ho Parkb,1, Wooram Parkc,1, Hyelim Kimd,1, Jong Geol Jange, Kyung Soo Honge, Jae-Young Leed, Hee Seung Seof, Dong Hee Nag, Tae-Hyung Kimh, Young Bin Choya, June Hong Ahne,*, Wonhwa Leeh,i,*, Chun Gwon Parkf,j,*
aDepartment of Biomedical Engineering, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea
bDepartment of Biotechnology and Bioengineering, Kangwon National University, Chuncheon, Gangwon-do, 24341, Republic of Korea
cDepartment of Biomedical-Chemical Engineering, The Catholic University of Korea, Bucheon, 14662, Republic of Korea
dCollege of Pharmacy, Chungnam National University, Daejeon, 34134, Republic of Korea
eDivision of Pulmonary and Allergy, Department of Internal Medicine, College of Medicine, Yeungnam University and Regional Center for Respiratory Diseases, Yeungnam University Medical Center, Daegu, 42415, Republic of Korea
fDepartment of Biomedical Engineering, SKKU Institute for Convergence, Sungkyunkwan University (SKKU), Suwon, 16419, Republic of Korea
gCollege of Pharmacy, Chung-Ang University, Seoul, 06974, Republic of Korea
hSchool of Integrative Engineering, Chung-Ang University, Seoul, 06974, Republic of Korea
iAging Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 34141, Republic of Korea
jBiomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, Suwon, 16419, Republic of Korea
1These authors contributed equally as first authors: Yun Young Lee, Hee Ho Park, Wooram Park, Hyelim Kim.
*Corresponding author.
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.
Keywords : COVID-19, Sepsis, DNase, Nanoparticles, NETosis
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