Preventing SARS-CoV-2 Infection Using Anti-spike Nanobody-IFN-β Conjugated Exosomes.
Preventing SARS-CoV-2 Infection Using Anti-spike Nanobody-IFN-β Conjugated Exosomes.
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DOI：
10.1007/s11095-022-03400-0
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发表时间：
2023-04
影响因子：
3.7
通讯作者：
Hanayama, Rikinari
中科院分区：
文献类型：
--
作者：
Lyu, Xiabing;Imai, Shota;Yamano, Tomoyoshi;Hanayama, Rikinari
为了抑制SARS-CoV-2的传播，我们开发了与抗刺突纳米抗体和I型干扰素β（IFN-β）缀合的工程化外泌体。我们评估了纳米抗体-IFN-β缀合的外泌体治疗SARS-CoV-2感染的功效和效力。乳脂球表皮生长因子8（MFG-E8）是一种糖蛋白，其结合暴露于外泌体上的磷脂酰丝氨酸（PS）。我们通过将抗刺突纳米抗体和IFN-β与MFG-E8融合来产生纳米抗体-IFN-β缀合的外泌体。我们使用SARS-CoV-2假病毒与编码ZsGreen的D 614 G突变体的刺突来模拟SARS-CoV-2的感染过程。在纳米抗体-IFN-β缀合的外泌体存在下，用表达血管紧张素转换酶-2（ACE 2）的腺癌人肺泡基底上皮细胞（A549）或表达ACE 2的HEK-蓝IFNα/β细胞感染SARS-CoV-2假病毒。通过评估靶细胞中ZsGreen的表达和感染细胞中干扰素刺激基因（ISG）的上调，我们评估了纳米抗体-IFN-β缀合的外来体的抗病毒作用。我们证实了抗刺突纳米抗体和IFN-β在外泌体上的表达。与纳米抗体-hIFN-β缀合的外泌体抑制了刺突蛋白与ACE 2之间的相互作用，从而抑制了SARS-CoV-2假病毒对宿主细胞的感染。同时，IFN-β被选择性地递送到SARS-CoV-2感染的细胞，导致ISGs表达上调。由于抗刺突纳米抗体和IFN-β的协同抗病毒作用，与纳米抗体-IFN-β缀合的外来体可在COVID-19的治疗中提供潜在益处。在线版本包含补充材料，可通过10.1007/s11095-022-03400-0获得。
To inhibit the transmission of SARS-CoV-2, we developed engineered exosomes that were conjugated with anti-spike nanobodies and type I interferon β (IFN-β). We evaluated the efficacy and potency of nanobody-IFN-β conjugated exosomes to treatment of SARS-CoV-2 infection. Milk fat globule epidermal growth factor 8 (MFG-E8) is a glycoprotein that binds to phosphatidylserine (PS) exposed on the exosomes. We generated nanobody-IFN-β conjugated exosomes by fusing an anti-spike nanobody and IFN-β with MFG-E8. We used the SARS-CoV-2 pseudovirus with the spike of the D614G mutant that encodes ZsGreen to mimic the infection process of the SARS-CoV-2. The SARS-CoV-2 pseudovirus was infected with angiotensin-converting enzyme-2 (ACE2) expressing adenocarcinomic human alveolar basal epithelial cells (A549) or ACE2 expressing HEK-blue IFNα/β cells in the presence of nanobody-IFN-β conjugated exosomes. By assessing the expression of ZsGreen in target cells and the upregulation of interferon-stimulated genes (ISGs) in infected cells, we evaluated the anti-viral effects of nanobody-IFN-β conjugated exosomes. We confirmed the anti-spike nanobody and IFN-β expressions on the exosomes. Exosomes conjugated with nanobody-hIFN-β inhibited the interaction between the spike protein and ACE2, thereby inhibiting the infection of host cells with SARS-CoV-2 pseudovirus. At the same time, IFN-β was selectively delivered to SARS-CoV-2 infected cells, resulting in the upregulation of ISGs expression. Exosomes conjugated with nanobody-IFN-β may provide potential benefits in the treatment of COVID-19 because of the cooperative anti-viral effects of the anti-spike nanobody and the IFN-β. The online version contains supplementary material available at 10.1007/s11095-022-03400-0.
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