Your browser doesn't support javascript.
Engineering Extracellular Vesicles Enriched with Palmitoylated ACE2 as COVID-19 Therapy.
Xie, Feng; Su, Peng; Pan, Ting; Zhou, Xiaoxue; Li, Heyu; Huang, Huizhe; Wang, Aijun; Wang, Fangwei; Huang, Jun; Yan, Haiyan; Zeng, Linghui; Zhang, Long; Zhou, Fangfang.
  • Xie F; School of Medicine, Zhejiang University City College, Hangzhou, 310015, China.
  • Su P; Institutes of Biology and Medical Science, Soochow University, Suzhou, 215123, China.
  • Pan T; MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China.
  • Zhou X; Center for Infection and Immunity Studies, School of Medicine, Sun Yat-sen University, Shenzhen, 518107, China.
  • Li H; MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China.
  • Huang H; MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China.
  • Wang A; Faculty of Basic Medical Sciences, Chongqing Medical University, Medical College Road 1, Chongqing, 400016, China.
  • Wang F; Department of Surgery, School of Medicine, UC Davis, Davis, CA, 95817, USA.
  • Huang J; MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China.
  • Yan H; MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China.
  • Zeng L; School of Medicine, Zhejiang University City College, Hangzhou, 310015, China.
  • Zhang L; School of Medicine, Zhejiang University City College, Hangzhou, 310015, China.
  • Zhou F; MOE Laboratory of Biosystems Homeostasis & Protection and Innovation Center for Cell Signaling Network, Life Sciences Institute, Zhejiang University, Hangzhou, 310058, China.
Adv Mater ; 33(49): e2103471, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1473796
ABSTRACT
Angiotensin converting enzyme 2 (ACE2) is a key receptor present on cell surfaces that directly interacts with the viral spike (S) protein of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). It is proposed that inhibiting this interaction can be promising in treating COVID-19. Here, the presence of ACE2 in extracellular vesicles (EVs) is reported and the EV-ACE2 levels are determined by protein palmitoylation. The Cys141 and Cys498 residues on ACE2 are S-palmitoylated by zinc finger DHHC-Type Palmitoyltransferase 3 (ZDHHC3) and de-palmitoylated by acyl protein thioesterase 1 (LYPLA1), which is critical for the membrane-targeting of ACE2 and their EV secretion. Importantly, by fusing the S-palmitoylation-dependent plasma membrane (PM) targeting sequence with ACE2, EVs enriched with ACE2 on their surface (referred to as PM-ACE2-EVs) are engineered. It is shown that PM-ACE2-EVs can bind to the SARS-CoV-2 S-RBD with high affinity and block its interaction with cell surface ACE2 in vitro. PM-ACE2-EVs show neutralization potency against pseudotyped and authentic SARS-CoV-2 in human ACE2 (hACE2) transgenic mice, efficiently block viral load of authentic SARS-CoV-2, and thus protect host against SARS-CoV-2-induced lung inflammation. The study provides an efficient engineering protocol for constructing a promising, novel biomaterial for application in prophylactic and therapeutic treatments against COVID-19.
Subject(s)
Keywords

Full text: Available Collection: International databases Database: MEDLINE Main subject: Extracellular Vesicles / COVID-19 Drug Treatment Limits: Animals Language: English Journal: Adv Mater Journal subject: Biophysics / Chemistry Year: 2021 Document Type: Article Affiliation country: Adma.202103471

Similar

MEDLINE

...
LILACS

LIS


Full text: Available Collection: International databases Database: MEDLINE Main subject: Extracellular Vesicles / COVID-19 Drug Treatment Limits: Animals Language: English Journal: Adv Mater Journal subject: Biophysics / Chemistry Year: 2021 Document Type: Article Affiliation country: Adma.202103471