Clinical discovery and validation of delivery vectors to empower cures for CNS diseases

& Abstract Developing efficient gene therapies and biologics can unlock new cures for neurological diseases, but is hindered by inefficient delivery, especially to the central nervous system (CNS). Traditional delivery vehicle discovery and validation pipelines rely on cellular and animal models that often fail to predict CNS delivery in patients. What is needed is to assess delivery efficacy in humans at the beginning of the discovery process. We propose to revolutionize the field by discovering and validating vectors in physiologically maintained deceased (PMD) human cadavers. Delivery vector performance in a PMD cadaver will provide confidence in their efficacy in humans and greatly reduce the reliance on preclinical animal discovery research, ultimately increasing the success of clinical trials. Our ethics-informed PMD platform will provide a blueprint for the safe, ethical, and just use of human donors in discovery research. Our discovery platform will help future researchers and clinicians find the most effective vectors to enable gene and biologic therapies that could be used to treat millions of patients with CNS indications. Project Number: 1RM1NS143853-01 | Fiscal Year: 2026 | NIH Institute/Center: National Institute of Neurological Disorders and Stroke (NINDS) | Principal Investigator: Claire Clelland (+1 co-PI) | Institution: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO, SAN FRANCISCO, CA | Award Amount: $2,656,684 | Activity Code: RM1 | Study Section: Special Emphasis Panel[ZRG1 BN-K (54)] View on NIH RePORTER: https://reporter.nih.gov/project-details/11211072