Bioengineering a Novel Therapeutic Transporter that Crosses the Blood Brain Barrier to Treat Brain Disorders

While the brain blood barrier (BBB) is an important physiological barrier that protects the brain, it is also represents a formable barrier to therapeutic delivery. Therefore, there is a critical need for therapeutic transporters that can be injected intravenously (i.v.), and effectively traverse the BBB and deliver therapeutic agents to the brain [1-8]. Cytonus Therapeutics has pioneered the development of a new bioinspired delivery agent (CargocytesTM) with potential to meet this critical need. Cargocytes are bioengineered enucleated mesenchymal stromal cells (MSCs) that specifically home to diseased tissues such as the brain and deliver therapeutic payloads following i.v. administration. Substantial work in our laboratory indicates that Cargocytes have potential to treat brain disorders as they readily extravasate through vascular barriers, invade endothelial basement membranes, and chemotax though complex extracellular matrices to target tissues deep within disease foci. Cargocytes can also be engineered to produce, secrete, and/or deliver a range of powerful therapeutics within the brain milieu including cytokines, neurotrophic factors, antibodies, nanobodies, RNAs, and even small molecule drugs. Overall, our findings demonstrate that Cargocytes are a new breakthrough technology platform for maximum local bioprotein delivery and production while minimizing systemic distribution. Cargocyte technology improves efficacy and reduces off-target toxicity, the “holy grail” of therapeutic delivery. The primary objective of this phase I application is to develop brain homing Cargocytes that cross the BBB using an established model of ischemic brain injury.There is a critical unmet need for cell-based therapeutics that can be administered intravenously (IV), and effectively home to and deliver therapeutic agents across the blood-brain barrier to patients after ischemic stroke, while maintaining patient safety. The objective of this Phase I application is to develop enucleated mesenchymal stem cells as therapeutics (Cargocyte) that home to the brain and demonstrate their ability to cross the blood-brain barrier in an established, clinically relevant mouse model of stroke.