Antibody-Biocide Fusions to Control Cryptosporidium

描述（由申请人提供）：本研究的目标是开发小隐孢子虫的治疗产品，这种产品可以在规模和成本上可行，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野外部署的武装部队所必需的。我们的方法是开发重组中和单克隆抗体和融合蛋白，将单克隆抗体与中和小孢子虫孢子子和分裂子的寄生蛋白（杀菌剂）遗传联系起来。我们将使用专有的逆转录载体基因转移技术将用于单克隆融合产物候选的多顺反子基因构建物插入细胞培养中。在体外和小鼠模型中鉴定出有效的产品后，我们将扩大细胞培养的生产规模，并通过创建转基因牛，在其乳汁中表达单克隆抗体和融合蛋白，并在新生小鼠和猪模型中测试抗隐孢子虫的功效。转基因表达将使抗隐孢子虫治疗药物的经济和大规模生产成为可能。除了生物防御应用外，开发的技术还将在治疗小梭菌和旅行者腹泻的机会性感染以及兽医使用中减少环境感染库方面具有重要的双重用途。

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.