Instituto de Biología Molecular y Celular de Plantas (IBMCP), Agencia Estatal Consejo Superior de Investigaciones Científicas, Universidad Politécnica de Valencia, Valencia, Spain.
Instituto Clodomiro Picado, Facultad de Microbiología, Universidad de Costa Rica, San José, Costa Rica.
Plant Biotechnol J. 2018 Mar;16(3):727-736. doi: 10.1111/pbi.12823. Epub 2017 Sep 22.
Antivenoms developed from the plasma of hyperimmunized animals are the only effective treatment available against snakebite envenomation but shortage of supply contributes to the high morbidity and mortality toll of this tropical disease. We describe a synthetic biology approach to affordable and cost-effective antivenom production based on plant-made recombinant polyclonal antibodies (termed pluribodies). The strategy takes advantage of virus superinfection exclusion to induce the formation of somatic expression mosaics in agroinfiltrated plants, which enables the expression of complex antibody repertoires in a highly reproducible manner. Pluribodies developed using toxin-binding genetic information captured from peripheral blood lymphocytes of hyperimmunized camels 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 snake venom toxins and has been shown to neutralize a wide range of toxin activities and provide protection against lethal venom doses in mice.
从高度免疫动物的血浆中开发的抗蛇毒血清是治疗蛇咬伤的唯一有效方法，但供应短缺导致这种热带疾病的发病率和死亡率居高不下。我们描述了一种基于植物制造的重组多克隆抗体（称为 pluribodies）的经济实惠且具有成本效益的抗蛇毒血清生产的合成生物学方法。该策略利用病毒超感染排除来诱导农杆菌浸润植物中体细胞表达嵌合体的形成，从而以高度可重复的方式表达复杂的抗体库。使用从高度免疫的骆驼外周血淋巴细胞中捕获的毒素结合遗传信息开发的 pluribodies重现了免疫反应的整体结合活性。此外，使用针对 Bothrops asper 蛇毒毒素的体外选择的 pluribody 配制了改良的植物抗蛇毒血清（plantivenom），并已证明它能中和广泛的毒素活性，并为小鼠提供针对致命毒液剂量的保护。
