A team at Children’s Hospital of Philadelphia (CHOP) reported a rare case of a neuroepithelial tumor associated with adeno-associated virus (AAV) integration following intracisternal magna vector delivery. The work, described by CHOP researchers at ASGCT and published in the New England Journal of Medicine, documents a fusion event linking AAV9 vector cassette sequences to the PLAG1 oncogene. The case involved a 5-year-old boy with severe MPS I deficiency (Hurler subtype) who received enzyme replacement therapy as an infant, underwent cord blood stem cell transplant, and then received gene therapy at 13 months using an AAV9 vector. At age five, routine imaging identified an intraventricular mass that was later surgically removed. Genetic analysis showed PLAG1 expression approximately 300 times higher than in other studied CNS tumors, and RNA sequencing identified the vector cassette fragment fused to exon 5 of PLAG1. Investigators reported no tumor growth at follow-up. The report adds to ongoing safety discussions in AAV gene therapy, emphasizing that while integration events have been seen in preclinical models, rare clinical events may require more attention to long-term monitoring and risk mitigation strategies.