Work

AAV-PHP.eB achieves superior neuronal transduction over AAV9 in pigtail macaques following intracerebroventricular administration

Year: 2025

Type: article

Abstract: . Employing a neuron-specific promoter and nuclear-localized reporter, we systematically quantified transduction across cortical, subcortical, and spinal regions. AAV-PHP.eB demonstrated significantly higher transduction rates in cortical and spinal regions compared to AAV9, despite similar expression patterns. Both vectors exhibited limited subcortical penetration and significant peripheral leakage, highlighting key challenges in CNS targeting. This is the first study to quantitatively compare AAV-PHP.eB and AAV9 in NHPs, providing valuable insights into the advantages and limitations of engineered AAV capsids for CNS gene therapy. These findings lay a critical foundation for optimizing vector designs and delivery strategies to improve outcomes in clinical applications for neurodegenerative and neurodevelopmental disorders.

Source: Molecular Therapy — Methods & Clinical Development

DOI: 10.1016/j.omtm.2025.101636