SBIR Phase I: Development of Brain-penetrant Non-viral Genome-editing Therapies for Central Nervous System Disorders

The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase I project addresses a significant unmet medical need for effective treatments of severe neurological disorders that currently have no cure. Neurological diseases such as Huntington's disease, Alzheimer's disease, and Parkinson's disease impact millions of people each year and could be effectively treated by genome editing therapeutics. This project will develop a non-viral genome editing delivery system that can safely and efficiently modify brain tissue, potentially halting disease progression rather than merely managing symptoms. By enabling a non-viral approach to deliver gene editing components to the brain, the technology has potential to reduce manufacturing complexity, avoid immune risks associated with viral vectors, and lower overall therapy costs. The resulting treatments could reach broader patient populations, improve quality of life, and reduce long-term healthcare burden. The approach is adaptable to multiple neurological disorders, representing a market of more than one million patients with genetically driven conditions. The technology will strengthen United States leadership in genome editing, support high-skill biotechnology employment, and enhance national capacity for translational research. This Small Business Innovation Research (SBIR) Phase I project aims to develop a non-viral genome editing delivery platform that can efficiently edit brain tissue. Current delivery methods for gene editing in the brain face significant challenges, including limited distribution, potential immune responses, and manufacturing complexity. This project will develop a system that combines a pre-formed genome editing enzyme with peptides that allow it to cross the blood brain barrier and selectively target neurons. The research will incorporate molecules that facilitate transport across the blood-brain barrier into the delivery platform and test them in laboratory models and animal studies. The project will also evaluate an alternative delivery method through the cerebrospinal fluid. The goal is to achieve at least 50% editing efficiency in brain neurons without direct injection into the brain tissue. If successful, this approach would enable treatment of a wide range of neurological disorders through less invasive administration methods, dramatically expanding the potential impact of genome editing therapies. The resulting platform would provide precise, durable genetic modification while minimizing risks associated with other delivery approaches. 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.