Many diseases that affect the central nervous system are intractable to conventional therapies and therefore require alternative treatments such as gene therapy. Such therapy requires absolute safety since the central nervous system is critical to survival. Choice of non-viral vectors such as naked plasmid DNA may have some merits. However, the transduction efficiencies of these vectors are extremely low. We have investigated the use of ultrasound to enhance the efficiency of naked plasmid DNA transfer. Using ultrasound, we targeted the central nervous system and found that insonation at 5.0W/cm2 for 5 seconds effectively transduced plasmid DNA into cultured slices of mouse brain. Since ultrasound successfully transduced naked plasmid DNA into neural tissue, our approach may hold significant promise for gene transfer to the central nervous system.