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

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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.