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用于病毒感染的电调控细胞干预。

Electrically regulated cell-based intervention for viral infections.

作者信息

Newmyer Sherri, Ssemadaali Marvin A, Radhakrishnan Harikrishnan, Javitz Harold S, Bhatnagar Parijat

机构信息

Biosciences Division SRI International Menlo Park California USA.

Education Division SRI International Menlo Park California USA.

出版信息

Bioeng Transl Med. 2022 Nov 15;8(2):e10434. doi: 10.1002/btm2.10434. eCollection 2023 Mar.

Abstract

This work reports on an engineered cell that-when electrically stimulated-synthesizes a desired protein, that is, . The platform has been used to express interferon (IFN)-β as a universal antiviral protein. Compelling evidence indicates the inevitability of new pandemics and drives the need for a pan-viral intervention that may be quickly deployed while more specific vaccines are in development. Toward this goal, a fast-growing mammalian cell () has been engineered with multiple synthetic elements. These include-(1) a voltage-gated Ca channel () that, upon sensing the electric field, activates the (2) Ca-mediated signaling pathway () to upregulate (3) IFN-β, via an engineered antiviral transgene (), that is, ➔. The antiviral effects of the ➔ have been validated on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected cells. The irradiated , that does not exhibit oncogenic capacity, continues to exert antiviral effect. The resulting ➔ uses a novel signaling pathway that, unlike the natural IFN synthesis pathway, is not subject to viral interference. Once clinically validated, the will be a universal antiviral cell therapy that can be immediately deployed in the event of an outbreak. The platform may also be useful in treating other diseases including cancer and autoimmune disorders.

摘要

这项工作报道了一种经过工程改造的细胞,当受到电刺激时,它能合成所需的蛋白质,即……该平台已被用于表达作为通用抗病毒蛋白的干扰素(IFN)-β。有力证据表明新的大流行不可避免,并推动了对一种泛病毒干预措施的需求,这种干预措施可以在更具针对性的疫苗研发期间迅速部署。为实现这一目标,一种快速生长的哺乳动物细胞()已被用多种合成元件进行了工程改造。这些元件包括:(1)一个电压门控钙通道(),在感知电场时,激活(2)钙介导的信号通路(),以通过一个经过工程改造的抗病毒转基因()上调(3)IFN-β,即→。→对严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染细胞的抗病毒作用已得到验证。经过辐照的不具有致癌能力,且继续发挥抗病毒作用。由此产生的→使用了一种新型信号通路,与天然IFN合成通路不同,该通路不受病毒干扰。一旦经过临床验证,将成为一种通用的抗病毒细胞疗法,可在疫情爆发时立即部署。该平台也可能有助于治疗包括癌症和自身免疫性疾病在内的其他疾病。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcce/10013824/5de4dbbc5459/BTM2-8-e10434-g004.jpg

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