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磷脂酶D在抗蛇毒血清开发中的生物技术潜力。

Biotechnological potential of Phospholipase D for antivenom development.

作者信息

Fingermann Matías, de Roodt Adolfo Rafael, Cascone Osvaldo, Miranda María Victoria

机构信息

Instituto Nacional de Producción de Biológicos (INPB), ANLIS "Dr. Carlos G. Malbrán", Vélez Sársfield 563, (1282) Buenos Aires, Argentina.

Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Godoy Cruz, 2290, (1425) Buenos Aires, Argentina.

出版信息

Toxicon X. 2020 Apr 18;6:100036. doi: 10.1016/j.toxcx.2020.100036. eCollection 2020 Jun.

Abstract

Loxoscelism is one of the most important forms of araneism in South America. The Health Authorities from countries with the highest incidence and longer history in registering loxoscelism cases indicate that specific antivenom should be administered during the first hours after the accident, especially in the presence or at risk of the most severe clinical outcome. Current antivenoms are based on immunoglobulins or their fragments, obtained from plasma of hyperimmunized horses. Antivenom has been produced using the same traditional techniques for more than 120 years. Although the whole composition of the spider venom remains unknown, the discovery and biotechnological production of the phospholipase D enzymes represented a milestone for the knowledge of the physiopathology of envenomation and for the introduction of new innovative tools in antivenom production. The fact that this protein is a principal toxin of the venom opens the possibility of replacing the use of whole venom as an immunogen, an attractive alternative considering the laborious techniques and low yields associated with venom extraction. This challenge warrants technological innovation to facilitate production and obtain more effective antidotes. In this review, we compile the reported studies, examining the advances in the expression and application of phospholipase D as a new immunogen and how the new biotechnological tools have introduced some degree of innovation in this field.

摘要

美洲毒蛛中毒是南美洲最重要的蜘蛛中毒形式之一。在美洲毒蛛中毒病例登记方面发病率最高且历史较长的国家的卫生当局指出,应在事故发生后的最初几个小时内注射特效抗蛇毒血清,尤其是在出现最严重临床后果或有此风险的情况下。目前的抗蛇毒血清基于从超免疫马的血浆中获得的免疫球蛋白或其片段。抗蛇毒血清采用相同的传统技术生产已有120多年。尽管蜘蛛毒液的完整成分仍不清楚,但磷脂酶D酶的发现和生物技术生产是了解中毒生理病理学以及在抗蛇毒血清生产中引入新创新工具的一个里程碑。这种蛋白质是毒液的主要毒素这一事实为替代使用全毒液作为免疫原提供了可能性,考虑到与毒液提取相关的繁琐技术和低产量,这是一个有吸引力的选择。这一挑战需要技术创新来促进生产并获得更有效的解毒剂。在这篇综述中,我们汇总了已报道的研究,审视了磷脂酶D作为一种新免疫原在表达和应用方面的进展,以及新的生物技术工具如何在该领域引入了一定程度的创新。

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