SBIR Phase II: Bacteriophage-Based Microbial Gene Therapy Platform for In Situ Engineering of Microbiomes

SBIR II 期：基于噬菌体的微生物基因治疗平台，用于微生物组的原位工程

• 批准号: 2126838
• 负责人: Michael Koeris
• 金额: $ 98.99万
• 依托单位: Vulcan Biologics, Inc.
• 依托单位国家: 美国
• 项目类别: Cooperative Agreement
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-15 至 2023-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2126838&HistoricalAwards=false
• 关键词: SBIR; Phase; II; Bacteriophage; Based

The broader impact of this Small Business Innovation Research (SBIR) Phase II project is to improve the health and quality of life for the 15-30 million Americans suffering from celiac disease (CD) and other gluten-related disorders, especially those with poor management of symptoms. Gluten-related disorders have a combined global prevalence of 5–10% and have been increasing over the past decade. Currently, the only effective treatment for these patients is adherence to a strict gluten-free diet, which fails to relieve symptoms in all patients and cannot prevent the severe gastrointestinal distress that follows accidental exposure. This project will advance a therapeutic solution to prevent persistent symptoms related to low-level or accidental gluten exposure. This will provide protection for people with CD and non-celiac gluten sensitivity when traveling, new patients adapting to a gluten-free diet, and individuals whose symptoms are poorly controlled despite adherence to a gluten-free diet. The proposed project will leverage a novel bacteriophage-based microbiome engineering platform to advance the development of a product to provide protection from gastrointestinal distress stemming from gluten exposure. To develop this therapeutic phage product, phages capable of infecting common gut bacteria like E. coli will be identified and engineered for efficient lysogenization. The phage or phage cocktail will be further engineered to express therapeutic modalities/proteins and tested in both human organoids derived from patients with CD and mouse models to demonstrate efficacy. The proposed work will provide a foundation for future extension of the platform to a wide range of microbiome-based applications.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

这项小型企业创新研究（SBIR）第二阶段项目的更广泛影响是改善患有乳糜泻（CD）和其他与麸质有关的疾病的15-300万美国人的健康和生活质量，尤其是那些症状管理不力的疾病。与麸质有关的疾病的总体流行率为5-10％，在过去十年中一直在增加。目前，这些患者的唯一有效治疗方法是遵守严格的无麸质饮食，该饮食无法缓解所有患者的症状，并且无法防止意外暴露后的严重胃肠道痛。该项目将推进一种治疗解决方案，以防止与低水平或意外面筋暴露有关的持续症状。这将为有CD和非素麸质敏感性的人提供保护，新患者适应无麸质饮食，以及其符号无法控制的目的地遵守无麸质饮食的人。拟议的项目将利用一种新型的基于细菌的微生物组工程平台来促进产品的开发，以提供防止因面筋暴露而产生的胃肠道遇险。为了开发这种治疗性噬菌体，将鉴定并设计能够感染常见肠道细菌（如大肠杆菌）的噬菌体，以有效地溶解液化。将进一步设计噬菌体或噬菌体鸡尾酒，以表达治疗方式/蛋白质，并在源自CD和小鼠模型的患者中衍生出的两个人体类器官，以证明有效性。拟议的工作将为将将平台的未来扩展到广泛的基于微生物组的应用程序提供基础。该奖项反映了NSF的法定任务，并使用基金会的知识分子优点和更广泛的影响评估标准，被认为是通过评估而被视为珍贵的支持。