SBIR-STTR Award

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 ?-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.

The broader impacts of this Small Business Technology Transfer (STTR) Phase II project could be both substantial and multifaceted, with far-reaching implications across the entire spectrum of healthcare, education, and environmental stewardship. This living pharmacy approach is an innovative and transformative cellular factory method of administering treatments and managing chronic diseases by maintaining steady-state drug levels over long periods of time without the need for frequent dosing. By synthesizing treatments directly within the body and replacing daily, weekly, or monthly dosing with a single dose, the technology has the potential to significantly enhance patient compliance, offering an alternative treatment modality that makes the disease invisible to daily life. Educationally, the proposed technology as a pioneering work may serve as a springboard for fostering innovation and research in the field of immuno-synthetic biology and biotechnology, paving the way for the next generation of scientists, researchers, and entrepreneurs to draw inspiration from nature?s design first. Scientifically, the platform could act as a testament to the exciting possibilities of symbiotic synthetic biology and the living pharmacy concept. This work spans the fields of immunology, microbiology, symbiotic biology, and synthetic biology, with potential dual applications in the defense industry and cancer prevention space. The proposed project aims to demonstrate the safety and tolerability of a novel and potentially harmless universal designer organism as a living pharmacy to treat diabetes and obesity in cats. Specifically, the plan is to demonstrate how a single injection can be effective for 12 weeks or longer to control blood glucose and weight gain for the companion animal market. This will serve as a model first, with the eventual goal of entering the human market. This cellular factory platform could facilitate a new era of cost-effective and patient-friendly treatments with fewer side effects and significantly decreased cascading effects, preventing severe complications and the onset of co-morbidities of many chronic diseases. This advancement holds substantial potential to curb the health crisis staged by an increasing number of obese and prediabetic individuals in the nation, thereby improving public health at a large scale. 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.