SBIR Phase I: Cell-derived vesicles loaded with novel anti-inflammatories for treatment of severe COVID-19

这个小企业创新研究第一阶段项目的更广泛的影响/商业潜力是为患有危及生命的医疗并发症的新冠肺炎患者提供一种新的治疗选择。冠状病毒感染会引起炎症反应，导致急性呼吸窘迫综合征、肺和器官衰竭。该项目建立在产生细胞衍生药物输送载体的新方法上，当与特殊分子结合时，这种载体专门针对炎症组织并改变疾病过程。这种候选药物还可能影响许多疾病的结果，在这些疾病中，失控的炎症是疾病病理的基础，例如新出现的病毒和/或细菌威胁、阿尔茨海默氏症和帕金森氏症、中风和心脏病、包括狼疮和关节炎在内的自身免疫性疾病以及各种癌症。这个小型企业创新研究第一阶段项目使用了一种新技术，利用应用于培养细胞的物理和化学力量来产生细胞衍生的囊泡。与最先进的技术相比，这项技术在产品产量、生成率和均匀性方面都有实质性的改进，并允许控制囊泡的大小。此外，囊泡可以从任何细胞系产生，以优化体内特定组织的囊泡趋向性。当这些囊泡装载了诱导炎症消退的分子，如溶血素，这些囊泡可能会产生一种新的治疗方法。拟议的工作将优化囊泡生产，执行囊泡表征，并开发有效的拆分加载程序。随后将评估肺损伤的细胞和动物模型中的组织特异性递送和功能。体外试验将测量囊泡与同源受体特异性结合的能力，并阻止中性粒细胞迁移和巨噬细胞产生促炎介质。疾病模型将监测携带解决素的囊泡阻断和逆转肺部炎症的能力。这一潜在的三重活动可能会产生另一种治疗模式。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project is to provide a novel treatment option for COVID-19 patients with life-threatening medical complications. Coronavirus infection causes inflammatory reactions leading to acute respiratory distress syndrome, lung and organ failure. This project builds on new methods to generate cell-derived drug delivery vehicles that, when combined with special molecules, specifically target inflamed tissues and modify the disease course. This drug candidate could also impact the outcome of many diseases where runaway inflammation underpins disease pathology, such as emerging viral and/or bacterial threats, neurological conditions such as Alzheimer’s and Parkinson’s disease, stroke and heart attack, autoimmune disease including lupus and arthritis, and various cancers. This Small Business Innovation Research Phase I project uses new technology that harnesses both physical and chemical forces applied to cultured cells to generate cell-derived vesicles. Compared to state-of-the-art techniques, this technology generates vesicles with substantial improvements in product yield, generation rate, and homogeneity, and allows control over vesicle size. Moreover, vesicles can be generated from any cell line to optimize vesicle tropism for specific tissues in the body. When loaded with molecules that induce inflammation-resolution such as resolvins, these vesicles could yield a new treatment. The proposed work will optimize vesicle production, perform vesicle characterization, and develop efficient resolvin-loading procedures. Tissue-specific delivery and functionality in cells and animal models of lung injury will subsequently be assessed. The in vitro assays will measure the ability of vesicles to specifically bind cognate receptors and block neutrophil migration and macrophage production of pro-inflammatory mediators. The disease model will monitor the capacity of resolvin-loaded vesicles to block and reverse inflammation in the lung. This potential triple activity could generate an alternate treatment modality.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.