Sonoporation: mechanical DNA delivery by ultrasonic cavitation

Development of nonviral gene transfer methods would be a valuable addition to the gene-therapy armamentarium, particularly for localized targeting of specific tissue volumes. Ultrasound can produce a variety of nonthermal bioeffects via acoustic cavitation including DNA delivery. Cavitation bubbles may induce cell death or transient membrane permeabilization (sonoporation) on a single cell level, as well as microvascular hemorrhage and disruption of tissue structure. Application of sonoporation for gene delivery to cells requires control of cavitation activity. Many studies have been performed using in vitro exposure systems, for which cavitation is virtually ubiquitous. In vivo, cavitation initiation and control is more difficult, but can be enhanced by cavitation nucleation agents, such as an ultrasound contrast agent. Sonoporation and ultrasonically enhanced gene delivery has been reported for a wide range of conditions including low frequency sonication (kilohertz frequencies), lithotripter shockwaves, HIFU, and even diagnostic ultrasound (megahertz frequencies). In vitro, a variety of cell lines has been successfully transfected, with concomitant cell killing. In vivo, initial applications have been to cancer gene therapy, for which cell killing can be a useful simultaneous treatment, and to cardiovascular disease. The use of ultrasound for nonviral gene delivery has been demonstrated for a robust array of in vitro and mammalian systems, which provides a fundamental basis and strong promise for development of new gene therapy methods for clinical medicine.