Successful targeted delivery of an AAV reporter via MRI-guided surgery to Göttingen Minipig® putamen; feasibility and tolerability

ASGCT 2026 -- Recent advances in MRI-guided clinical techniques for targeted gene and cell therapy delivery to the brain have necessitated nonclinical in vivo safety studies that emulate clinical procedures to support first-in-human investigation. Neurodegeneration of disease specific brain regions, including the putamen in Parkinson’s and Huntington’s diseases, underscores the need for precise, localized delivery strategies for gene replacement or disease modifying therapies. While administration into the cerebrospinal fluid can achieve central nervous system (CNS) exposure, it often results in broad parenchymal and systemic distribution. In contrast, using clinically established surgical approaches to target disease relevant parenchymal structures enables focused delivery to the intended anatomical site. Nonclinical in vivo studies employing these clinically relevant targeting strategies provide a critical translational bridge, supporting safety assessment and procedural alignment for first-in-human application. The Göttingen minipig has emerged as a human-relevant alternative for first-in-human translational bridging.