Antibody-Biocide Fusions to Control Cryptosporidium

描述(申请人提供)：这项研究的目标是开发微小隐孢子虫的治疗产品，这种产品可以按规模和成本生产，可以提供给大量患者或处于危险中的个人，这可能是打击生物恐怖主义或保护战地部署的武装部队所必需的。我们的方法是开发重组中和单抗，以及将单抗与杀寄生虫蛋白(杀生剂)基因连接的融合蛋白，这些蛋白中和微小弧菌的子孢子和裂殖子。我们将使用专有的逆转录载体基因转移技术，将候选单克隆融合产物的多顺反子基因结构插入细胞培养。在鉴定了在体外和小鼠模型中有效的产品后，我们将扩大细胞培养的生产，创造在乳汁中表达单抗和融合蛋白的转基因牛，并在新生小鼠和猪模型中测试抗隐孢子虫的效果。转基因表达将使抗隐孢子虫治疗药物的生产变得经济和大规模。除了生物防御应用外，开发的技术还将在治疗细小弧菌和旅行者腹泻的机会性感染以及减少环境感染的兽医方面具有重要的两用应用。

DESCRIPTION (provided by applicant): The goal of this research is develop therapeutic products for Cryptosporidium parvum which can be made at a scale and cost which are feasible for delivery to large populations of patients or individuals at risk, as may be necessary in countering bioterrorism, or in protecting field-deployed armed forces. Our approach is to develop recombinant neutralizing monoclonal antibodies, and fusion proteins that genetically link monoclonal antibodies to parasiticidal proteins (biocides) which neutralize C. parvum sporozoites and merozoites. We will use a proprietary retrovector gene transfer technology to insert multicistronic gene constructs for the monoclonal fusion product candidates into cell culture. Following identification of products effective in vitro and in mouse models, we will scale up production in cell culture and by creation of transgenic cattle that express the monoclonal antibodies and fusion proteins in their milk and test anti-cryptosporidial efficacy in neonatal mice and pig models. Transgenic expression will enable manufacture of anti-cryptosporidial therapeutics economically and on a large scale. In addition to biodefense applications, the technology developed will also have important dual-use application in treatment of opportunistic infections with C. parvum and traveler's diarrhea, and in veterinary use to reduce the environmental reservoir of infection.