An approach to rapid distributed manufacturing of broad spectrum anti-viral griffithsin using cell-free systems to mitigate pandemics.

An approach to rapid distributed manufacturing of broad spectrum anti-viral griffithsin using cell-free systems to mitigate pandemics.
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DOI:
10.1016/j.nbt.2023.04.003
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发表时间:
2023-09-25
期刊:
影响因子:
5.4
通讯作者:
Rao, Govind
Rao, Govind
中科院分区:
工程技术2区
文献类型:
--
作者:
Borhani, Shayan G.;Levine, Max Z.;Krumpe, Lauren H.;Wilson, Jennifer;Henrich, Curtis J.;Keefe, Barry R. O.;Lo, Donald C.;Sittampalam, Sitta;Godfrey, Alexander G.;Lunsford, R. Dwayne;Mangalampalli, Venkata;Tao, Dingyin;LeClair, Christopher A.;Thole, Aaron P.;Frey, Douglas;Swartz, James;Rao, Govind

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本研究描述了广谱抗病毒蛋白griffithsin(GRFT)的无细胞生物制造,使得其可以在不到24小时内以微克量产生,具有一致的纯度和效力。我们证明GRFT生产使用两个独立的无细胞系统,一种植物和一种微生物。使用标准监管指标验证了Griffithsin纯度和质量。在体外证实了对SARS-CoV-2和HIV-1的有效性,并且与体内表达的GRFT几乎相同。拟议的生产工艺是有效的,可以很容易地扩大规模,并部署在任何可能出现病毒病原体的地方。目前SARS-CoV-2病毒变异体的出现导致现有疫苗的频繁更新和一线单克隆抗体治疗的疗效丧失。GRFT等蛋白质具有有效和广泛的病毒中和能力,提供了一种引人注目的大流行缓解策略,可在爆发源头迅速抑制病毒出现。
This study describes the cell-free biomanufacturing of a broad-spectrum antiviral protein, griffithsin (GRFT) such that it can be produced in microgram quantities with consistent purity and potency in less than 24 hours. We demonstrate GRFT production using two independent cell-free systems, one plant and one microbial. Griffithsin purity and quality were verified using standard regulatory metrics. Efficacy was demonstrated in vitro against SARS-CoV-2 and HIV-1 and was nearly identical to that of GRFT expressed in vivo. The proposed production process is efficient and can be readily scaled up and deployed wherever a viral pathogen might emerge. The current emergence of viral variants of SARS-CoV-2 has resulted in frequent updating of existing vaccines and loss of efficacy for front-line monoclonal antibody therapies. Proteins such as GRFT with its efficacious and broad virus neutralizing capability provide a compelling pandemic mitigation strategy to promptly suppress viral emergence at the source of an outbreak.
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