STTR Phase I: Fibroblast-Derived Engineered Extracellular Vesicles (eEVs) as New Nucleic Acid Therapeutic Delivery Systems for Peripheral Nervous System (PNS) Genetic Disorders

The broader impact/commercial potential of this Small Business Technology Transfer (STTR) Phase I project lies in its ability to advance gene therapy for neurological disorders by developing a scalable and cost-effective manufacturing process for extracellular vesicle (EV)-based therapeutics. This innovation has the potential to improve treatment safety, precision, and accessibility for patients with conditions such as neurofibromatosis type 1 (NF1), addressing a critical unmet medical need. By streamlining production methods, this project aims to lower the cost of EV-based therapies, making them more widely available. Additionally, the technology is expected to drive growth in the U.S. biotechnology sector, fostering job creation and reinforcing the nation's leadership in gene therapy innovation. The commercial potential is significant, as this approach may enable the development of novel, non-viral gene therapies with broad applications in precision medicine. This Small Business Technology Transfer (STTR) Phase I project seeks to address key technical challenges in the scalable manufacturing of EV-based gene therapies. The research focuses on improving methods for EV isolation, purification, and cargo loading to enhance therapeutic efficacy. Specific objectives include optimizing culture conditions, refining chemical transfection protocols, and developing standardized procedures for loading exogenous DNA into EVs. The project will also evaluate biodistribution, dosing, and therapeutic outcomes in preclinical models to support future clinical translation. Anticipated technical results include the establishment of reproducible, scalable manufacturing protocols and the demonstration of in vitro efficacy. This work will contribute to the broader field of precision medicine by providing an alternative to viral vectors for gene delivery, addressing current limitations in safety, scalability, and immune response. 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.