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Secreted Expression of mRNA-Encoded Truncated ACE2 Variants for SARS-CoV-2 via Lipid-Like Nanoassemblies.
Li, Min; Li, Sanpeng; Huang, Yixuan; Chen, Haixia; Zhang, Songya; Zhang, Zhicheng; Wu, Weigang; Zeng, Xiaobin; Zhou, Boping; Li, Bin.
  • Li M; Department of Infectious Disease, Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, China.
  • Li S; Department of Infectious Disease, Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, China.
  • Huang Y; Department of Infectious Disease, Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, China.
  • Chen H; Department of Clinical Laboratory, The Second Clinical Medical College of Jinan University, Shenzhen, 518020, China.
  • Zhang S; Shenzhen Institute of Synthetic Biology, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China.
  • Zhang Z; Department of Infectious Disease, Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, China.
  • Wu W; Department of Infectious Disease, Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, China.
  • Zeng X; Department of Infectious Disease, Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, China.
  • Zhou B; Department of Infectious Disease, Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, China.
  • Li B; Department of Infectious Disease, Shenzhen People's Hospital, The First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, 518020, China.
Adv Mater ; 33(34): e2101707, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1316189
ABSTRACT
The transfer of foreign synthetic messenger RNA (mRNA) into cells is essential for mRNA-based protein-replacement therapies. Prophylactic mRNA COVID-19 vaccines commonly utilize nanotechnology to deliver mRNA encoding SARS-CoV-2 vaccine antigens, thereby triggering the body's immune response and preventing infections. In this study, a new combinatorial library of symmetric lipid-like compounds is constructed, and among which a lead compound is selected to prepare lipid-like nanoassemblies (LLNs) for intracellular delivery of mRNA. After multiround optimization, the mRNA formulated into core-shell-structured LLNs exhibits more than three orders of magnitude higher resistance to serum than the unprotected mRNA, and leads to sustained and high-level protein expression in mammalian cells. A single intravenous injection of LLNs into mice achieves over 95% mRNA translation in the spleen, without causing significant hematological and histological changes. Delivery of in-vitro-transcribed mRNA that encodes high-affinity truncated ACE2 variants (tACE2v mRNA) through LLNs induces elevated expression and secretion of tACE2v decoys, which is able to effectively block the binding of the receptor-binding domain of the SARS-CoV-2 to the human ACE2 receptor. The robust neutralization activity in vitro suggests that intracellular delivery of mRNA encoding ACE2 receptor mimics via LLNs may represent a potential intervention strategy for COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Phosphatidylethanolamines / RNA, Messenger / Nanoparticles / Galactosidases / COVID-19 Vaccines / SARS-CoV-2 Type of study: Prognostic study Topics: Vaccines / Variants Limits: Animals / Female / Humans Language: English Journal: Adv Mater Journal subject: Biophysics / Chemistry Year: 2021 Document Type: Article Affiliation country: Adma.202101707

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Phosphatidylethanolamines / RNA, Messenger / Nanoparticles / Galactosidases / COVID-19 Vaccines / SARS-CoV-2 Type of study: Prognostic study Topics: Vaccines / Variants Limits: Animals / Female / Humans Language: English Journal: Adv Mater Journal subject: Biophysics / Chemistry Year: 2021 Document Type: Article Affiliation country: Adma.202101707