Abstract: Methods, systems, and devices for promoting ultrasound-mediated gene transfection in vivo are disclosed. The methods and devices of the invention administer a gene formulation to the subject; and apply ultrasound energy to the subject, such that cell transfection is promoted. The ultrasound energy can be provided by an external source or an ultrasound source disposed inside the subject's body. For example, the source of ultrasound energy can be disposed on a catheter. The compositions suitable for ultrasound-mediated transfection can include genes (and plasmids containing such genes) in a pharmaceutically acceptable carrier and/or liposomes suitable for injection into a target site, as well as implantable degradable matrix carriers.