Researchers at Children’s Hospital of Philadelphia (CHOP) described a rare brain-tumor case linked to adeno-associated virus (AAV) integration after intracisternal magna vector delivery. The work, presented by Lindsey George, MD, at ASGCT and published in the New England Journal of Medicine, details a 5-year-old boy treated for severe MPS1 deficiency who later developed an intraventricular mass. Molecular analysis showed the tumor was PLAG1-driven, with AAV9 vector cassette sequence fused to exon 5 of the PLAG1 gene. CHOP reported successful surgery with no tumor growth at follow-up and noted the patient’s advanced neurocognitive function. While AAV integration events have been reported in animal models, the clinical case adds pressure for the field to strengthen long-term monitoring and to better characterize when and how integration might occur after CNS-directed AAV delivery.