Inhalable dry powder mRNA vaccines based on extracellular vesicles

被引：123

作者：

Popowski, Kristen D. ^{[1
,2
]}

Moatti, Adele ^{[2
,3
,4
]}

Scull, Grant ^{[2
,3
,4
]}

Silkstone, Dylan ^{[2
,3
,4
]}

Lutz, Halle ^{[1
,2
]}

Abad, Blanca Lopez de Juan ^{[1
]}

George, Arianna ^{[5
,6
]}

Belcher, Elizabeth ^{[3
,4
]}

Zhu, Dashuai ^{[1
,2
]}

Mei, Xuan ^{[1
,2
,3
,4
]}

Cheng, Xiao ^{[1
,3
,4
]}

Cislo, Megan ^{[6
,7
]}

Ghodsi, Asma ^{[1
]}

Cai, Yuheng ^{[2
,3
,4
]}

Huang, Ke ^{[1
,2
,3
,4
]}

Li, Junlang ^{[1
,3
,4
]}

Brown, Ashley C. ^{[2
,3
,4
]}

Greenbaum, Alon ^{[2
,3
,4
]}

Dinh, Phuong-Uyen C. ^{[1
,2
]}

Cheng, Ke ^{[1
,2
,3
,4
,8
]}

机构：

[1] North Carolina State Univ, Dept Mol Biomed Sci, Raleigh, NC 27607 USA

[2] North Carolina State Univ, Comparat Med Inst, Raleigh, NC 27607 USA

[3] Univ North Carolina Chapel Hill, Joint Dept Biomed Engn, Raleigh, NC 27607 USA

[4] North Carolina State Univ, Raleigh, NC 27607 USA

[5] North Carolina State Univ, Dept Mol & Struct Biochem, Raleigh, NC 27695 USA

[6] North Carolina State Univ, Dept Biol Sci, Raleigh, NC 27695 USA

[7] North Carolina State Univ, Dept Food Bioproc & Nutr Sci, Raleigh, NC 27695 USA

[8] Univ North Carolina Chapel Hill, Div Pharmacoengn & Mol Pharmaceut, Chapel Hill, NC 27599 USA

来源：

MATTER | 2022年 / 5卷 / 09期

基金：

美国国家卫生研究院;

关键词：

LUNG SPHEROID CELLS; DELIVERY; EXOSOMES; AUTOFLUORESCENCE;

D O I：

10.1016/j.matt.2022.06.012

中图分类号：

T [工业技术];

学科分类号：

08 ;

摘要：

Respiratory diseases are a global burden, with millions of deaths attributed to pulmonary illnesses and dysfunctions. Therapeutics have been developed, but they present major limitations regarding pulmonary bioavailability and product stability. To circumvent such limitations, we developed room-temperature-stable inhalable lung -derived extracellular vesicles or exosomes (Lung-Exos) as mRNA and protein drug carriers. Compared with standard synthetic nano -particle liposomes (Lipos), Lung-Exos exhibited superior distribu-tion to the bronchioles and parenchyma and are deliverable to the lungs of rodents and nonhuman primates (NHPs) by dry powder inhalation. In a vaccine application, severe acute respiratory corona -virus 2 (SARS-CoV-2) spike (S) protein encoding mRNA-loaded Lung-Exos (S-Exos) elicited greater immunoglobulin G (IgG) and secretory IgA (SIgA) responses than its loaded liposome (S-Lipo) counterpart. Importantly, S-Exos remained functional at room-temperature stor-age for one month. Our results suggest that extracellular vesicles can serve as an inhaled mRNA drug-delivery system that is superior to synthetic liposomes.

引用

页码：2960 / 2974

页数：16

共 49 条

[1] Freeze-drying of nanoparticles: Formulation, process and storage considerations [J].

Abdelwahed, Wassim ;

Degobert, Ghania ;

Stainmesse, Serge ;

Fessi, Hatem .

ADVANCED DRUG DELIVERY REVIEWS, 2006, 58 (15) :1688-1713

[2] Nanomedicine and the COVID-19 vaccines [J].

不详 .

NATURE NANOTECHNOLOGY, 2020, 15 (12) :963-963

[3] Colloidal systems for drug delivery: from design to therapy [J].

Beija, Mariana ;

Salvayre, Robert ;

Lauth-de Viguerie, Nancy ;

Marty, Jean-Daniel .

TRENDS IN BIOTECHNOLOGY, 2012, 30 (09) :485-496

[4] Trehalose prevents aggregation of exosomes and cryodamage [J].

Bosch, Steffi ;

de Beaurepaire, Laurence ;

Allard, Marie ;

Mosser, Mathilde ;

Heichette, Claire ;

Chretien, Denis ;

Jegou, Dominique ;

Bach, Jean-Marie .

SCIENTIFIC REPORTS, 2016, 6

[5] SARS-CoV-2 mRNA vaccine design enabled by prototype pathogen preparedness [J].

Corbett, Kizzmekia S. ;

Edwards, Darin K. ;

Leist, Sarah R. ;

Abiona, Olubukola M. ;

Boyoglu-Barnum, Seyhan ;

Gillespie, Rebecca A. ;

Himansu, Sunny ;

Schafer, Alexandra ;

Ziwawo, Cynthia T. ;

DiPiazza, Anthony T. ;

Dinnon, Kenneth H. ;

Elbashir, Sayda M. ;

Shaw, Christine A. ;

Woods, Angela ;

Fritch, Ethan J. ;

Martinez, David R. ;

Bock, Kevin W. ;

Minai, Mahnaz ;

Nagata, Bianca M. ;

Hutchinson, Geoffrey B. ;

Wu, Kai ;

Henry, Carole ;

Bahl, Kapil ;

Garcia-Dominguez, Dario ;

Ma, LingZhi ;

Renzi, Isabella ;

Kong, Wing-Pui ;

Schmidt, Stephen D. ;

Wang, Lingshu ;

Zhang, Yi ;

Phung, Emily ;

Chang, Lauren A. ;

Loomis, Rebecca J. ;

Altaras, Nedim Emil ;

Narayanan, Elisabeth ;

Metkar, Mihir ;

Presnyak, Vlad ;

Liu, Cuiping ;

Louder, Mark K. ;

Shi, Wei ;

Leung, Kwanyee ;

Yang, Eun Sung ;

West, Ande ;

Gully, Kendra L. ;

Stevens, Laura J. ;

Gully, Kendra L. ;

Wang, Nianshuang ;

Wrapp, Daniel ;

Doria-Rose, Nicole A. ;

Stewart-Jones, Guillaume .

NATURE, 2020, 586 (7830) :567-+

[6] A pre-investigational new drug study of lung spheroid cell therapy for treating pulmonary fibrosis [J].

Cores, Jhon ;

Dinh, Phuong-Uyen C. ;

Hensley, Taylor ;

Adler, Kenneth B. ;

Lobo, Leonard J. ;

Cheng, Ke .

STEM CELLS TRANSLATIONAL MEDICINE, 2020, 9 (07) :786-798

[7] Safety and Efficacy of Allogeneic Lung Spheroid Cells in a Mismatched Rat Model of Pulmonary Fibrosis [J].

Cores, Jhon ;

Hensley, M. Taylor ;

Kinlaw, Kathryn ;

Rikard, S. Michaela ;

Phuong-Uyen Dinh ;

Paudel, Dipti ;

Tang, Junnan ;

Vandergriff, Adam C. ;

Allen, Tyler A. ;

Li, Yazhou ;

Liu, Jianhua ;

Niu, Bo ;

Chi, Yuepeng ;

Caranasos, Thomas ;

Lobo, Leonard J. ;

Cheng, Ke .

STEM CELLS TRANSLATIONAL MEDICINE, 2017, 6 (10) :1905-1916

[8] The potential of mesenchymal stem cell therapy for chronic lung disease [J].

Cruz, Fernanda Ferreira ;

Macedo Rocco, Patricia Rieken .

EXPERT REVIEW OF RESPIRATORY MEDICINE, 2020, 14 (01) :31-39

[9] Characterizing and Diminishing Autofluorescence in Formalin-fixed Paraffin-embedded Human Respiratory Tissue [J].

Davis, A. Sally ;

Richter, Anke ;

Becker, Steven ;

Moyer, Jenna E. ;

Sandouk, Aline ;

Skinner, Jeff ;

Taubenberger, Jeffery K. .

JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY, 2014, 62 (06) :405-423

[10] Inhalation of lung spheroid cell secretome and exosomes promotes lung repair in pulmonary fibrosis [J].

Dinh, Phuong-Uyen C. ;

Paudel, Dipti ;

Brochu, Hayden ;

Popowski, Kristen D. ;

Gracieux, M. Cyndell ;

Cores, Jhon ;

Huang, Ke ;

Hensley, M. Taylor ;

Harrell, Erin ;

Vandergriff, Adam C. ;

George, Arianna K. ;

Barrio, Raina T. ;

Hu, Shiqi ;

Allen, Tyler A. ;

Blackburn, Kevin ;

Caranasos, Thomas G. ;

Peng, Xinxia ;

Schnabel, Lauren V. ;

Adler, Kenneth B. ;

Lobo, Leonard J. ;

Goshe, Michael B. ;

Cheng, Ke .

NATURE COMMUNICATIONS, 2020, 11 (01)

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