Focused ultrasound (FUS) is a targeted and noninvasive technique that can be used to activate gas-filled microbubbles (MBs) to oscillate within the bloodstream. This technique has been used previously to open the blood-brain barrier (BBB) to facilitate the delivery of therapeutics to the surrounding brain tissue. However, disruption of the BBB may be contraindicated in certain disease contexts. Here, we utilize low pressure FUS to oscillate the MBs just enough to transfect endothelial cells, without opening the BBB. The low pressure FUS regimen results in enhanced gene delivery to endothelial cells, with none of the inflammatory or immune pathway upregulation observed at higher FUS pressures.