Weighing the Risks of Lentiviral Gene Therapy for Cerebral Adrenoleukodystrophy

More than 30 years ago, the first transplantation with autologous hematopoietic stem cells modified with integrated murine retroviral vectors carrying potentially therapeutic genes was performed in patients with serious human disorders. The past decade has been marked by an acceleration in the publication of data from clinical trials and in regulatory approvals for therapies that use viral gene addition to treat hemoglobinopathies, immunodeficiencies, and metabolic neurologic disorders such as cerebral adrenoleukodystrophy.1 After the induction of numerous hematologic cancers linked to activation or dysregulation of nearby oncogenes by viral promoter–enhancers contained within the retroviral vector among patients enrolled in early clinical . . .