PMID- 36216580
OWN - NLM
STAT- MEDLINE
DCOM- 20221229
LR  - 20230106
IS  - 2198-3844 (Electronic)
IS  - 2198-3844 (Linking)
VI  - 9
IP  - 35
DP  - 2022 Dec
TI  - Rapid Generation of Circulating and Mucosal Decoy Human ACE2 using mRNA 
      Nanotherapeutics for the Potential Treatment of SARS-CoV-2.
PG  - e2202556
LID - 10.1002/advs.202202556 [doi]
LID - 2202556
AB  - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause lethal 
      pulmonary damage in humans. It contains spike proteins on its envelope that bind 
      to human angiotensin-converting enzyme 2 (hACE2) expressed on airway cells, 
      enabling entry of the virus, and causing infection. The soluble form of hACE2 
      binds SARS-CoV-2 spike protein, prevents viral entry into target cells, and 
      ameliorates lung injury; however, its short half-life limits therapeutic 
      utilities. Here, synthetic mRNA is engineered to encode a soluble form of hACE2 
      (hsACE2) to prevent viral infection. A novel lipid nanoparticle (LNP) is used for 
      packaging and delivering mRNA to cells to produce hsACE2 proteins. Intravenously 
      administered LNP delivers mRNA to hepatocytes, leading to the production of 
      circulatory hsACE2 initiated within 2 h and sustained over several days. Inhaled 
      LNP results in lung transfection and secretion of mucosal hsACE2 to lung 
      epithelia, the primary site of entry and pathogenesis for SARS-CoV-2. 
      Furthermore, mRNA-generated hsACE2 binds to the receptor-binding domain of the 
      viral spike protein. Finally, hsACE2 effectively inhibits SARS-CoV-2 and its 
      pseudoviruses from infecting host cells. The proof of principle study shows that 
      mRNA-based nanotherapeutics can be potentially deployed to neutralize SARS-CoV-2 
      and open new treatment opportunities for coronavirus disease 2019 (COVID-19).
CI  - (c) 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.
FAU - Kim, Jeonghwan
AU  - Kim J
AUID- ORCID: 0000-0002-1697-5107
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, Robertson Life 
      Sciences Building, Oregon State University, Portland, OR, 97201, USA.
FAU - Jozic, Antony
AU  - Jozic A
AUID- ORCID: 0000-0001-6249-2328
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, Robertson Life 
      Sciences Building, Oregon State University, Portland, OR, 97201, USA.
FAU - Mukherjee, Anindit
AU  - Mukherjee A
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, Robertson Life 
      Sciences Building, Oregon State University, Portland, OR, 97201, USA.
FAU - Nelson, Dylan
AU  - Nelson D
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, Robertson Life 
      Sciences Building, Oregon State University, Portland, OR, 97201, USA.
AD  - High-Throughput Screening Services Laboratory, College of Pharmacy, Oregon State 
      University, Corvallis, OR, 97331, USA.
FAU - Chiem, Kevin
AU  - Chiem K
AD  - Disease Prevention and Intervention, and Population Health Programs, Texas 
      Biomedical Research Institute, San Antonio, TX, 78227, USA.
FAU - Khan, Md Siddiqur Rahman
AU  - Khan MSR
AD  - Disease Prevention and Intervention, and Population Health Programs, Texas 
      Biomedical Research Institute, San Antonio, TX, 78227, USA.
FAU - Torrelles, Jordi B
AU  - Torrelles JB
AUID- ORCID: 0000-0001-7702-5941
AD  - Disease Prevention and Intervention, and Population Health Programs, Texas 
      Biomedical Research Institute, San Antonio, TX, 78227, USA.
FAU - Martinez-Sobrido, Luis
AU  - Martinez-Sobrido L
AUID- ORCID: 0000-0001-7084-0804
AD  - Disease Prevention and Intervention, and Population Health Programs, Texas 
      Biomedical Research Institute, San Antonio, TX, 78227, USA.
FAU - Sahay, Gaurav
AU  - Sahay G
AUID- ORCID: 0000-0003-1071-0500
AD  - Department of Pharmaceutical Sciences, College of Pharmacy, Robertson Life 
      Sciences Building, Oregon State University, Portland, OR, 97201, USA.
AD  - Department of Biomedical Engineering, Robertson Life Sciences Building, Oregon 
      Health & Science University, Portland, OR, 97201, USA.
AD  - Department of Ophthalmology, Casey Eye Institute, Oregon Health & Science 
      University, Portland, OR, 97239, USA.
LA  - eng
GR  - R01 HL146736/HL/NHLBI NIH HHS/United States
GR  - 1R01HL146736-01 (G.S)/National Heart Lung and Blood Institute (NHLBI)/
GR  - SAHAY19XX0/Cystic Fibrosis Foundation/
GR  - SAHAY18G0 (G.S)/Cystic Fibrosis Foundation/
PT  - Journal Article
DEP - 20221010
PL  - Germany
TA  - Adv Sci (Weinh)
JT  - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
JID - 101664569
RN  - EC 3.4.17.23 (Angiotensin-Converting Enzyme 2)
RN  - 0 (spike protein, SARS-CoV-2)
RN  - 0 (RNA, Messenger)
RN  - 0 (Lipid Nanoparticles)
SB  - IM
UOF - bioRxiv. 2020 Jul 25;:. PMID: 32743574
MH  - Humans
MH  - *Angiotensin-Converting Enzyme 2/biosynthesis/blood/genetics
MH  - *COVID-19/therapy
MH  - *SARS-CoV-2/enzymology
MH  - *RNA, Messenger/administration & dosage/genetics
PMC - PMC9762296
OTO - NOTNLM
OT  - COVID-19
OT  - gene therapy
OT  - human soluble ACE2
OT  - lipid nanoparticles
OT  - messenger RNA
COIS- G.S. is a coinventor in patent application US20200129445A1 that details LNP-Sito. 
      G.S. is a cofounder of EnterX Bio and RNAvax Bio, and has an advisory role to 
      Saliogen Therapeutics Inc., Rare Air Inc., and Sanofi.
EDAT- 2022/10/11 06:00
MHDA- 2022/12/22 06:00
PMCR- 2022/10/10
CRDT- 2022/10/10 21:42
PHST- 2022/09/19 00:00 [revised]
PHST- 2022/05/06 00:00 [received]
PHST- 2022/10/11 06:00 [pubmed]
PHST- 2022/12/22 06:00 [medline]
PHST- 2022/10/10 21:42 [entrez]
PHST- 2022/10/10 00:00 [pmc-release]
AID - ADVS4640 [pii]
AID - 10.1002/advs.202202556 [doi]
PST - ppublish
SO  - Adv Sci (Weinh). 2022 Dec;9(35):e2202556. doi: 10.1002/advs.202202556. Epub 2022 
      Oct 10.