Engineered extracellular vesicles directed to the spike protein inhibit SARS-CoV-2.

Engineered extracellular vesicles directed to the spike protein inhibit SARS-CoV-2.
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DOI:
10.1016/j.omtm.2022.01.015
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发表时间:
2022-03-10
期刊:
Molecular therapy. Methods & clinical development
影响因子:
--
通讯作者:
Morris KV
Morris KV
中科院分区:
其他
文献类型:
--
作者:
Scott TA;Supramaniam A;Idris A;Cardoso AA;Shrivastava S;Kelly G;Grepo NA;Soemardy C;Ray RM;McMillan NAJ;Morris KV

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SARS-CoV-2(CoV-2)病毒感染导致COVID-19疾病,其在全球范围内造成显著的发病率和死亡率。疫苗对于遏制SARS-CoV-2的传播至关重要,而治疗SARS-CoV-2和COVID-19疾病的持续和重新出现的感染将需要治疗药物。目前还没有针对COVID-19的市售有效抗病毒疗法,这促使人们开发新的治疗方法。在这里,我们描述了一种特异性靶向中和SARS-CoV-2的分子疗法,该疗法由细胞外囊泡(EV)组成,该囊泡含有嵌入抗CoV-2纳米抗体内的新型融合四跨膜蛋白CD 63。这些富含抗CoV-2的EV在受体结合域(RBD)位点结合SARS-CoV-2刺突蛋白,并且可以功能性地中和SARS-CoV-2。这项工作展示了一种创新的EV靶向平台,可用于靶向和抑制SARS-CoV-2感染的早期阶段。本文描述了一种模块化细胞外囊泡(EV)平台,其可以将EV重定向至靶向病毒包膜蛋白,以及这些病毒靶向EV广泛中和所关注的SARS-COV-2变体的能力。
SARS-CoV-2 (CoV-2) viral infection results in COVID-19 disease, which has caused significant morbidity and mortality worldwide. A vaccine is crucial to curtail the spread of SARS-CoV-2, while therapeutics will be required to treat ongoing and reemerging infections of SARS-CoV-2 and COVID-19 disease. There are currently no commercially available effective anti-viral therapies for COVID-19, urging the development of novel modalities. Here, we describe a molecular therapy specifically targeted to neutralize SARS-CoV-2, which consists of extracellular vesicles (EVs) containing a novel fusion tetraspanin protein, CD63, embedded within an anti-CoV-2 nanobody. These anti-CoV-2-enriched EVs bind SARS-CoV-2 spike protein at the receptor-binding domain (RBD) site and can functionally neutralize SARS-CoV-2. This work demonstrates an innovative EV-targeting platform that can be employed to target and inhibit the early stages of SARS-CoV-2 infection. Described here is a modular extracellular vesicle (EV) platform that can redirect EVs to target virus envelope proteins and the ability of these virus-targeted EVs to broadly neutralize SARS-COV-2 variants of concern.
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