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为户外种植做准备:格里菲斯菌素可在青贮饲料中表达并在储存后保持活性。

In Preparation for Outdoor Pharming: Griffithsin Can Be Expressed in and Retains Activity After Storage as Silage.

作者信息

Eapen Paul, Cates Jennifer, Mundell Rich, Palmer Kenneth E, Fuqua Joshua L

机构信息

University of Louisville School of Medicine, University of Louisville, Louisville, KY, United States.

University of Kentucky College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY, United States.

出版信息

Front Bioeng Biotechnol. 2020 Mar 18;8:199. doi: 10.3389/fbioe.2020.00199. eCollection 2020.

Abstract

Griffithsin is an algae-derived lectin with strong anti-viral activity against HIV and a positive safety profile. Multiple clinical studies are investigating griffithsin's utility as topical HIV microbicide. HIV microbicides are an extremely cost-sensitive market and plant-based griffithsin protein expression has the potential to meet those demands. The griffithsin product used in the clinic has been expressed and purified in , using a TMV-based viral vector system, Geneware®. Outdoor pharming of biopharmaceuticals would further alleviate startup costs for biotechnology firms and may allow broader product accessibility. Therefore, this study assessed expression in a hybrid tobacco line, , that is susceptible to TMV-based viral vectors and can be grown outdoors. In addition to using this hybrid line we expand on methods for storage of griffithsin in leafy plants by ensiling kilogram quantities of griffithsin. The ensiling process allows year-round biomanufacturing, minimal environmental-controlled storage, and reduces the industry need for multiple growth areas to maintain multi-product manufacturing of plant-based pharmaceuticals. This study shows that griffithsin can be expressed in and is stable, recoverable, and active from ensiled tissue. These studies can pave the way for future plant-based pharmaceuticals to be expressed and stored in this manner.

摘要

格里菲斯素是一种源自藻类的凝集素,对HIV具有强大的抗病毒活性,且安全性良好。多项临床研究正在探究格里菲斯素作为局部HIV杀微生物剂的效用。HIV杀微生物剂市场对成本极为敏感,基于植物的格里菲斯素蛋白表达有潜力满足这些需求。临床使用的格里菲斯素产品已通过基于烟草花叶病毒(TMV)的病毒载体系统Geneware®在[具体生物]中表达和纯化。生物制药的户外种植将进一步减轻生物技术公司的启动成本,并可能使产品更容易获得。因此,本研究评估了在一种对基于TMV的病毒载体敏感且可在户外种植的杂交烟草品系[具体品系]中的表达情况。除了使用这种杂交品系外,我们还通过青贮数千克的格里菲斯素,扩展了在叶类植物中储存格里菲斯素的方法。青贮过程允许全年进行生物制造,减少环境控制储存,并降低了该行业对多个种植区域以维持基于植物的药物多产品生产的需求。本研究表明,格里菲斯素可以在[具体品系]中表达,并且在青贮组织中是稳定的、可回收的且具有活性。这些研究可为未来以这种方式表达和储存基于植物的药物铺平道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2de8/7093594/a5c68e285d4f/fbioe-08-00199-g0001.jpg

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