SBIR Phase I: A Platform for Anthelmintic Drug Discovery using DAF-12 as a Novel Target

SBIR 第一阶段：使用 DAF-12 作为新靶点的驱虫药物发现平台

• 批准号: 1315836
• 负责人: Christopher Hopkins
• 金额: $ 15万
• 依托单位: Knudra Diagnostics
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1315836&HistoricalAwards=false
• 关键词: SBIR; Phase; Platform; Anthelmintic; Drug

This Small Business Innovation Research (SBIR) Phase I project creates a drug-screening platform for discovery of new antiparasitic drugs. Resistance to current drug treatments is on the rise. New antiparasitic drugs under development are mostly focused on neurotransmission targets, yet a new target has recently emerged, the daf-12 gene. Knudra uses a core expertise in nematode bioengineering to insert parasite genes into the C. elegans roundworm. Drug candidates are found against the parasite gene by the use of biosensor backgrounds, which use fluorescent gene-expression reporters that turn red upon detection of antiparasitic activity. Phase I feasibility is demonstrated when known agonist and antagonist of DAF-12 elicit expected activity on the parasite gene. The platform may then be used to screen compound libraries to find candidates for anthelmintic use.The broader impact/commercial potential of this project, if successful, will be the creation of a screening platform for finding antiparasitics to help in the battle against important diseases such as elephantiasis, river blindness, trichinosis, Enterobiasis (pinworm), and parasitic infections in livestock and crops. Parasitic infection in livestock and humans currently are treated with more than 20 drugs on the market, but some are toxic and carry black box warnings. Food and health security throughout the world would be enhanced with the development of new antiparasites that are safer and more effective. In addition, the technology will help to bring clarity of understanding to the biology of infective-state formation in parasite lifecycle.

这个小企业创新研究（SBIR）第一阶段项目创建了一个药物筛选平台，用于发现新的抗寄生虫药物。对目前药物治疗的耐药性正在上升。正在开发的新型抗寄生虫药物大多集中在神经传递靶点上，然而最近出现了一个新的靶点daf-12基因。Knudra利用线虫生物工程的核心专业知识，将寄生虫基因插入C。秀丽线虫通过使用生物传感器背景来发现针对寄生虫基因的候选药物，所述生物传感器背景使用在检测到抗寄生虫活性时变红的荧光基因表达报告物。当已知的DAF-12激动剂和拮抗剂引发寄生虫基因的预期活性时，第一阶段的可行性得到了证明。该平台可用于筛选化合物库，以寻找驱虫药的候选药物。如果成功，该项目更广泛的影响/商业潜力将是创建一个筛选平台，用于寻找抗寄生虫药，以帮助对抗重要疾病，如象皮病，河盲症，旋毛虫病，蛲虫病（蛲虫），以及牲畜和作物的寄生虫感染。目前，市场上有20多种药物可以治疗牲畜和人类的寄生虫感染，但有些药物有毒，并带有黑盒警告。 随着更安全、更有效的新型抗寄生虫药的开发，全世界的粮食和健康安全将得到加强。 此外，该技术将有助于澄清寄生虫生命周期中感染状态形成的生物学。