STTR Phase I: Development of a novel system to manufacture therapies inside the human body

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The broader impact of this Small Business Technology Transfer (STTR) Phase I project is to improve drug delivery by developing a system to synthesize much needed drug therapies directly in patients. This advancement, if successful, would reduce the need for complex and expensive manufacturing, eliminate the reliance on refrigerated drug shipment and storage, and remove need for repeated injections. Development of such a system would be adaptable for different applications across human health and disease, would be resistant to supply chain disruptions caused by pandemics or natural disasters, and would result in the equitable delivery of medications to diverse patient populations across the globe. The proposed project seeks to develop a dynamic living medicine capable of supporting the delivery of biological drugs directly in vivo. Over the last decade, many attempts have been made to deliver biologics safely and efficiently to humans using engineered bacteria and viruses as living medicines. The current system is fraught with problems, mostly stemming from the immunogenicity of these vectors. This critical technological and innovation gap - the manufacture biologics directly in vivo safely for extended periods of time - may be achieved through the genetic engineering of avirulent organism symbionts to express proteins of interest. In this study, blood symbionts will be genetically engineered to expresses either β-glucocerebrosidase or insulin, with the goal of generating living medicines to treat Gaucher’s disease and diabetes, respectively. The secretion, activity, and durability of the engineered compounds will be assessed in vitro and in vivo. The safety and efficacy of this therapeutic approach will be assessed in pre-clinical models.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.