南方科技大学知识苑(SUSTech KC): Secreted Expression of mRNA-Encoded Truncated ACE2 Variants for SARS-CoV-2 via Lipid-Like Nanoassemblies

题名	Secreted Expression of mRNA-Encoded Truncated ACE2 Variants for SARS-CoV-2 via Lipid-Like Nanoassemblies
作者	Li, Min1 ; Li, Sanpeng 1; Huang, Yixuan 1; Chen, Haixia 2; Zhang, Songya 3; Zhang, Zhicheng 1; Wu, Weigang 1; Zeng, Xiaobin 1; Zhou, Boping 1; Li, Bin1,4
通讯作者	Li, Bin
发表日期	2021-07-01
DOI	10.1002/adma.202101707
发表期刊	ADVANCED MATERIALS 影响因子和分区
ISSN	0935-9648
EISSN	1521-4095
摘要	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.
关键词	lipid-like nanoassemblies messenger RNA SARS-CoV-2 spleen-targeted delivery systems truncated ACE2 decoys
相关链接	[来源记录]
收录类别	SCI ; EI
语种	英语
重要成果	NI论文
学校署名	第一 ; 通讯
资助项目	National Natural Science Foundation of China[82072053] ; Shenzhen Science and Technology Program[RCYX20200714114539061] ; Shenzhen Fundamental Research Foundation[JCYJ20190806150018265]
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
WOS类目	Chemistry, Multidisciplinary ; Chemistry, Physical ; Nanoscience & Nanotechnology ; Materials Science, Multidisciplinary ; Physics, Applied ; Physics, Condensed Matter
WOS记录号	WOS:000674179200001
出版者	WILEY-V C H VERLAG GMBH
ESI学科分类	MATERIALS SCIENCE
来源库	Web of Science
引用统计	被引频次[WOS]：25
成果类型	期刊论文
条目标识符	http://sustech.caswiz.com/handle/2SGJ60CL/240230
专题	南方科技大学第一附属医院
作者单位	1.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen Peoples Hosp, Dept Infect Dis, Shenzhen 518020, Peoples R China 2.Jinan Univ, Clin Med Coll 2, Dept Clin Lab, Shenzhen 518020, Peoples R China 3.Chinese Acad Sci, Shenzhen Inst Adv Technol, Shenzhen Inst Synthet Biol, Shenzhen 518055, Peoples R China 4.Jinan Univ, Clin Med Coll 2, Dept Infect Dis, Shenzhen 518020, Peoples R China
第一作者单位	南方科技大学第一附属医院
通讯作者单位	南方科技大学第一附属医院
第一作者的第一单位	南方科技大学第一附属医院
推荐引用方式 GB/T 7714	Li, Min,Li, Sanpeng,Huang, Yixuan,et al. Secreted Expression of mRNA-Encoded Truncated ACE2 Variants for SARS-CoV-2 via Lipid-Like Nanoassemblies[J]. ADVANCED MATERIALS,2021.
APA	Li, Min.,Li, Sanpeng.,Huang, Yixuan.,Chen, Haixia.,Zhang, Songya.,...&Li, Bin.(2021).Secreted Expression of mRNA-Encoded Truncated ACE2 Variants for SARS-CoV-2 via Lipid-Like Nanoassemblies.ADVANCED MATERIALS.
MLA	Li, Min,et al."Secreted Expression of mRNA-Encoded Truncated ACE2 Variants for SARS-CoV-2 via Lipid-Like Nanoassemblies".ADVANCED MATERIALS (2021).