SBIR Phase II: A Platform for Anthelmintic Drug Discovery using Genome-modified C. elegans

这个小企业创新研究（SBIR）第二阶段项目的更广泛的影响/商业潜力是开发一个发现新的驱虫（抗寄生虫）药物的平台。 目前市场上的所有驱虫药都存在耐药性。 目前的药物开发只是将新分子引入现有的药物靶点。 因此，耐药性迅速转移到这些新药上，使其在上市后不久就失效。 如果没有足够的有效驱虫药来源，牲畜产量、作物损失和人力资本开始受到影响。社会负担正在全世界造成总计数千亿美元的经济损失。 通过专注于控制进入感染性生命形式的新型药物靶标，该提案旨在产生一类新的驱虫药来解决这一日益严重的问题。将这类潜在的新型驱虫药商业化的制药公司每年将获得15 B美元或更多的市场潜力。SBIR第二阶段项目建议开发一个平台，用于使用基因工程药物发现新的驱虫药（C。elegans）。 所使用的方法将插入寄生虫基因的一段来替换天然基因的一段。 由此产生的嵌合体基因将C.将线虫转化为更好地模仿寄生虫状态的形式。 然后通过测试针对寄生虫感染模型的功效将发现对表达嵌合体的线虫有活性的药物命中物精制成先导物。 该提案的嵌合体平台适用于各种寄生虫基因。 由此产生的多样化平台有望为发现和最终引入一类具有广谱活性的新型抗寄生虫药物提供快速途径。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project is the development of a platform for the discovery of new anthelmintic (anti-parasite) drugs. Drug resistance is occurring with all anthelmintics currently on the market. Current drug development only introduces new molecules to the existing drug targets. As a result, drug resistance quickly jumps to these new drugs, which makes them ineffective shortly after market introduction. Without an adequate source of effective anthelmintics, livestock yields, crop damage, and human capital are starting to suffer. The social burden is creating economic losses totaling hundreds of billions of dollars worldwide. By focusing on a novel drug target that controls entry into infective life forms, this proposal aims to generate a new class of anthelmintics to combat this growing problem. The drug companies that commercialize this potential new class of anthelmintics will access a market potential of $1.5 B per year or more.The SBIR Phase II project proposes to develop a platform for the discovery of new anthelmintic drugs using genetically engineered nematods (C. elegans). The approach used will insert a segment of a parasite gene in replacement of a segment of a native gene. The resulting chimera gene converts the C. elegans nematode into a form that better mimics the parasite state. Drug hits found active on the chimera-expressing nematode are then refined into leads by testing for efficacy against parasite infection model. The proposal's chimera platform is adapted to a diverse set of parasite genes. The resulting diverse platform is expected to provide a rapid path to discovery and eventual introduction of a novel class of anti-parasite drugs with broad-spectrum activity.