Engineering Cellular Biosensors with Customizable Antiviral Responses Targeting Hepatitis B Virus
Engineering Cellular Biosensors with Customizable Antiviral Responses Targeting Hepatitis B Virus
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DOI：
10.1016/j.isci.2020.100867
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发表时间：
2020-03-27
期刊：
影响因子：
5.8
通讯作者：
Ryo, Akihide
中科院分区：
文献类型：
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作者：
Matsunaga, Satoko;Jeremiah, Sundararaj S.;Ryo, Akihide
SynNotch受体技术是一种多功能工具，其使用具有细胞外scFv和细胞内转录因子的调节缺口核心部分，使得能够在哺乳动物细胞中编程定制的输入和输出功能。在这项研究中，我们设计了一种新的synNotch受体，包括与细胞内人工转录因子连接的抗HBs抗原的scFv，并将其用于病毒传感和细胞免疫治疗。synNotch受体表达细胞感知HBV颗粒和膜结合的HBs抗原，并通过表达报告分子secNL或GFP作出反应。我们还对这些细胞进行了编程，以分配抗病毒反应，如I型干扰素和抗HBV中和鼠-人嵌合抗体。我们的数据显示，synNotch受体信号传导适用于膜结合配体，如包膜病毒颗粒和脂质体囊泡上携带的蛋白质。这项研究建立了“工程免疫”的概念，其中synNotch平台用于针对病毒感染的细胞免疫疗法。
SynNotch receptor technology is a versatile tool that uses the regulatory notch core portion with an extracellular scFv and an intracellular transcription factor that enables to program customized input and output functions in mammalian cells. In this study, we designed a novel synNotch receptor comprising scFv against HBs antigen linked with an intracellular artificial transcription factor and exploited it for viral sensing and cellular immunotherapy. The synNotch receptor expressing cells sensed HBV particles and membrane-bound HBs antigens and responded by expressing reporter molecules, secNL or GFP. We also programmed these cells to dispense antiviral responses such as type I interferon and anti-HBV neutralizing mouse-human chimeric antibodies. Our data reveal that synNotch receptor signaling works for membrane-bound ligands such as enveloped viral particles and proteins borne on liposomal vesicles. This study establishes the concepts of "engineered immunity'' where the synNotch platform is utilized for cellular immunotherapy against viral infections.