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Plant Biotechnol J:在植物中实现反复高效生产抗蛇毒血清

已有 2976 次阅读 2017-9-25 09:17 |个人分类:每日摘要|系统分类:论文交流|关键词:学者

A synthetic biology approach for consistent production of plant-made recombinant polyclonal antibodies against snake venom toxins


First author:Jose Manuel Julve Parreño; Affiliations: Universidad Politécnica de Valencia (瓦伦西亚理工大学): Valencia, Spain

Corresponding author: Diego Orzáez


Antivenoms (抗蛇毒血清) developed from the plasma (血浆) of hyperimmunized (超免疫) animals are the only effective treatment available against snakebite (蛇咬伤) envenomation (毒液螫入) but shortage of supply contributes to the high morbidity (发病率) and mortality toll of this tropical disease (热带病). We describe a synthetic biology approach to affordable and cost-effective (性价比高) antivenom production based on plant-made recombinant polyclonal antibodies (termed pluribodies 多克隆抗体). The strategy takes advantage of virus superinfection (病毒感染) exclusion to induce the formation of somatic expression mosaics in agroinfiltrated plants (农杆菌渗入植株), which enables the expression of complex antibody repertoires (抗体谱) in a highly reproducible (可再生的) manner. Pluribodies developed using toxin-binding (毒素结合) genetic information captured from peripheral blood lymphocytes (外周血淋巴细胞) of hyperimmunized camels (骆驼) recapitulated the overall binding activity of the immune response. Furthermore, an improved plant-made antivenom (plantivenom) was formulated using an in vitro selected pluribody against Bothrops asper (三色矛头蝮) snake venom toxins (蛇毒毒素) and has been shown to neutralize (中和) a wide range of toxin activities and provide protection against lethal venom doses (致命的毒液剂量) in mice.


从超免疫动物血浆中提取的抗蛇毒血清是唯一对蛇毒液螫入有效的治疗,但由于供应短缺,这个热带疾病的发病率高居不下。本文作者基于植物重组多克隆抗体构建了一套可行且性价比较高的生物合成方法用以生产抗蛇毒血清。这个方法利用了病毒感染排除在农杆菌渗入植株中诱导镶嵌体的体内表达,这可以使复杂抗体谱的表达重复实现。多克隆抗体使用从高免疫骆驼外周血淋巴细胞获取的毒素结合遗传信息获取免疫响应的所有结合活性。此外,作者还利用离体选择的三色矛头蝮蛇毒毒素选择的多克隆抗体构建了升级版的植物制造的抗蛇毒血清,该血清在小鼠中可中和多种毒素活性,并对摄入致命毒液剂量下的小鼠提供保护。


通讯:Diego Orzáez (http://www.ibmcp.upv.es/FGB/people/diego.html)


个人简介:在Granell实验室完成博士学业,方向是植物程序性细胞死亡;在瓦赫宁根E. Woltering的实验室完成博士后,方向是植物培养细胞的程序性细胞死亡;然后到荷兰瓦赫宁根大学A. Schot的LMA实验室,开始将植物作为生物工厂制造抗体;2004年回到瓦伦西亚,并在2008年获得终身教职。


研究方向:基因工程与合成生物学。


doi: 10.1111/pbi.12823


Journal: Plant Biotechnology Journal
First Published data: September 22, 2017.


P.S. 欢迎关注微信公众号:微信号Plant_Frontiers


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