Tagged extracellular vesicles with the RBD of the viral spike protein for delivery of antiviral agents against SARS-COV-2 infection.
Tagged extracellular vesicles with the RBD of the viral spike protein for delivery of antiviral agents against SARS-COV-2 infection.
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用病毒刺突蛋白的 RBD 标记细胞外囊泡，用于递送抗 SARS-COV-2 感染的抗病毒药物
DOI：
10.1016/j.jconrel.2021.05.049
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发表时间：
2021-07-10
期刊：
影响因子：
--
通讯作者：
Xiong S
中科院分区：
文献类型：
--
作者：
Fu Y;Xiong S
COVID-19的全球传播凸显了对快速开发针对SARS-CoV-2的治疗和药物的有效方法的迫切需求。细胞外囊泡（Extracellular vesicle，EV）通过表面膜蛋白之间的特异性相互作用被组织细胞识别和内吞，之后它们递送其分子货物。这提供了在EV表面修饰膜蛋白的潜力，作为用于特异性组织靶向和药物递送的有前途的手段。在这项研究中，我们描述了一种基于VSVG病毒假型的方法来加载EV膜与病毒刺突蛋白的受体结合结构域（RBD），SARS-CoV-2附着，融合和细胞进入的关键结构域。RBD标记的EV可以特异性识别靶细胞表面的ACE 2受体，这是RBD标记的EV细胞摄取和靶向所需的。此外，使用hACE 2转基因小鼠模型，我们显示RBD标记的EV在高度表达ACE 2的靶组织中特异性积累。最后，我们证明了RBD标记的EV封装针对SARS-CoV-2假病毒的siRNA可以特异性地靶向肺组织并抑制体内的假病毒感染。总之，我们的工作提出了一种安全有效的工程EV系统，用于将潜在的抗病毒剂体内靶向递送到特定组织中，作为针对SARS-CoV-2感染的治疗潜力。
The worldwide spread of COVID-19 highlights the urgent need for an efficient approach to rapidly develop therapeutics and prophylactics against SARS-CoV-2. Extracellular vesicle(EVs) are recognized and endocytosed by tissue cells via specific interactions between surface membrane proteins, where after they deliver their molecular cargo. This provides the potential to modify membrane proteins at EV surfaces as a promising means for specific tissue targeting and drug delivery. In this study, we describe a VSVG viral pseudotyping-based approach to load EV membranes with the receptor-binding domain (RBD) of the viral spike protein, the key domain in SARS-CoV-2 attachment, fusion and cellular entry. The RBD-tagged EVs can specifically recognize ACE2 receptor on the surface of target cells, which is required for the RBD-tagged EVs cellular uptake and targeting. Further, using the hACE2 transgenic mouse model, we show the RBD-tagged EVs accumulate specifically in the target tissues that highly express ACE2. Finally, we demonstrate that the RBD-tagged EVs that encapsulate siRNAs against SARS-CoV-2 pseudovirus can specifically target lung tissues and suppress the pseudovirus infection in vivo. Together, our work presents a safe and effective engineered EV system for in vivo targeted delivery of potential antiviral agents into specific tissues which as a therapeutic potential against SARS-CoV-2 infection.
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影响因子：
46.9
作者：
Alvarez-Erviti, Lydia;Seow, Yiqi;Wood, Matthew J. A.
通讯作者：
Wood, Matthew J. A.
影响因子：
3.7
作者：
Kuate S;Cinatl J;Doerr HW;Uberla K
通讯作者：
Uberla K
外泌体作为帕金森氏病疗法的药物。
DOI：
10.1016/j.jconrel.2015.03.033
发表时间：
2015-06-10
期刊：
Journal of controlled release : official journal of the Controlled Release Society
影响因子：
--
作者：
Haney MJ;Klyachko NL;Zhao Y;Gupta R;Plotnikova EG;He Z;Patel T;Piroyan A;Sokolsky M;Kabanov AV;Batrakova EV
通讯作者：
Batrakova EV
影响因子：
56.9
作者：
Lv, Zhe;Deng, Yong-Qiang;Wang, Xiangxi
通讯作者：
Wang, Xiangxi
DOI：
10.1002/jbm.b.30648
发表时间：
2007-04-01
影响因子：
3.4
作者：
Heinrich, Laurence;Freyria, Anne-Marie;Hartmann, Daniel Jean
通讯作者：
Hartmann, Daniel Jean