Antibody-Biocide Fusions to Control Cryptosporidium

抗体-杀菌剂融合来控制隐孢子虫

• 批准号: 7115180
• 负责人: MICHAEL IMBODEN
• 金额: $ 114.12万
• 依托单位: IOGENETICS, LLC
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-08-01 至 2008-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7115180
• 关键词: Cryptosporidium; biotechnology; cell line; chimeric proteins; cow; cryptosporidiosis; cyclic GMP; disease /disorder prevention /control; genetically modified animals; hybridomas; immunologic substance development /preparation; laboratory mouse; monoclonal antibody; neutralizing antibody; newborn animals; protozoal toxin; recombinant proteins; swine; tissue /cell culture; transfection; transfection /expression vector

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.

描述（由申请人提供）：这项研究的目的是开发用于隐孢子虫的治疗产品，该产品可以按比例和成本制定，这些产品对于应对生物恐怖主义或保护野外部署的大量患者或有危险的患者或有危险的人来说是可行的，这是必要的。 我们的方法是开发中和中和单克隆抗体的重组和融合蛋白，这些抗体将单克隆抗体与寄生虫蛋白（杀菌剂）（中和孢子虫孢子虫和蛋白酶）联系起来。我们将使用专有的逆转录子基因转移技术来插入单克隆融合产物候选物的多发性基因构建体中，并将​​其插入细胞培养中。在鉴定出有效的体外和小鼠模型中的产品后，我们将通过在牛奶中表达单克隆抗体和融合蛋白的转基因牛来扩展生产，并在其牛奶中测试抗晶体小鼠和猪模型中的抗晶体孢子效应。转基因表达将使经济和大规模地生产抗晶状体治疗剂。除了生物化的应用外，开发的技术还将在用于治疗parvum和Traveler腹泻的机会性感染方面以及兽医用途，以减少感染的环境储层。