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.