The blood-brain barrier (BBB) is an imposing foe for gene therapy. Formed of cells wedged tightly together, the BBB keeps toxins and pathogens that may be present in the blood from entering brain tissue, but it also keeps out potential treatment for diseases that affect the central nervous system (CNS). Researchers have discovered some delivery vehicles — known as adeno-associated viruses (AAV) — that can cross the barrier under certain circumstances, but most of the time, AAVs are inefficient at ferrying gene therapies across. Investigators are now working to optimize AAVs as gene delivery vehicles, improving their efficiency and their potential to deliver drugs to treat brain cancers such as glioblastoma and genetic diseases that affect the central nervous system.