Evaluation of AAV transduction efficiency via multiple delivery routes: Insights from peripheral and central nervous system analysis

This study evaluates the biodistribution and transduction efficiency of adeno-associated virus serotype 9 (AAV9) vectors administered via intracerebroventricular (ICV), intra-arterial (IA), and intravenous (IV) routes in a murine model. Quantitative assessments of green fluorescent protein (GFP) expression were conducted to compare transduction efficacy across central nervous system (CNS) and peripheral tissues. The results demonstrate that high-dose ICV administration resulted in robust GFP expressions in the hippocampus and fimbria, indicating effective CNS targeting. Conversely, when administered intravenously (IV), the distribution of the drug was more widespread, affecting peripheral organs such as the liver and lungs, with limited penetration of the CNS. IA delivery achieved a balanced distribution, facilitating moderate transduction in both CNS and peripheral tissues. These findings underscore the significance of selecting appropriate administration routes to optimize AAV-mediated gene delivery for specific therapeutic targets. The study also underscores the necessity for quantitative analyses to accurately assess transduction efficiencies, informing the development of targeted gene therapies for neurological disorders.