A research team from the University of Rochester Medicine and the University of Copenhagen reported an in vivo AAV approach designed to reach brain targets by harnessing the glymphatic system and improving specificity for human glial progenitor cells. Published in Nature Biotechnology, the work uses engineered AAV5 capsids, screened in mouse brains engrafted with human glial progenitors. The platform aims to tackle two recurring barriers in brain gene therapy: crossing the blood-brain barrier and avoiding off-target transduction. Investigators tracked vector performance in vivo to identify variants that preferentially infect human glial progenitor cells and their descendants, including astrocytes and oligodendrocytes. If replicated in disease settings, the glymphatic-targeting strategy could become a delivery template for neurological programs where glial dysfunction is central, potentially influencing next-generation selection of AAV capsids and delivery routes.