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以大米为基础的口服抗体片段预防和治疗轮状病毒感染。

Rice-based oral antibody fragment prophylaxis and therapy against rotavirus infection.

机构信息

Division of Mucosal Immunology, Department of Microbiology and Immunology, The Institute of Medical Science, University of Tokyo, Tokyo, Japan.

出版信息

J Clin Invest. 2013 Sep;123(9):3829-38. doi: 10.1172/JCI70266. Epub 2013 Aug 8.

Abstract

Rotavirus-induced diarrhea is a life-threatening disease in immunocompromised individuals and in children in developing countries. We have developed a system for prophylaxis and therapy against rotavirus disease using transgenic rice expressing the neutralizing variable domain of a rotavirus-specific llama heavy-chain antibody fragment (MucoRice-ARP1). MucoRice-ARP1 was produced at high levels in rice seeds using an overexpression system and RNAi technology to suppress the production of major rice endogenous storage proteins. Orally administered MucoRice-ARP1 markedly decreased the viral load in immunocompetent and immunodeficient mice. The antibody retained in vitro neutralizing activity after long-term storage (>1 yr) and boiling and conferred protection in mice even after heat treatment at 94°C for 30 minutes. High-yield, water-soluble, and purification-free MucoRice-ARP1 thus forms the basis for orally administered prophylaxis and therapy against rotavirus infections.

摘要

轮状病毒引起的腹泻是免疫功能低下个体和发展中国家儿童的一种危及生命的疾病。我们已经开发出一种使用表达轮状病毒特异性 llama 重链抗体片段(MucoRice-ARP1)的中和可变结构域的转基因水稻来预防和治疗轮状病毒病的系统。MucoRice-ARP1 在水稻种子中使用过表达系统和 RNAi 技术以抑制主要水稻内源储存蛋白的产生而高水平生产。口服给予 MucoRice-ARP1 可显著降低免疫功能正常和免疫缺陷小鼠的病毒载量。该抗体在长期储存(>1 年)和煮沸后保留体外中和活性,并在小鼠中提供保护,即使在 94°C 下加热 30 分钟后也是如此。高产量、水溶性且无需纯化的 MucoRice-ARP1 因此为口服预防和治疗轮状病毒感染奠定了基础。

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