Gene Delivery Using Ultrasound Contrast Agents

Abstract

With the human genome product and continuing advances in molecular biology many therapeutic genes have been discovered. In the cardiovascular system, gene therapy has the potential to improve myocardial vascularization and ameliorate congestive heart failure. For successful development of clinical gene therapy, however, effective gene delivery vectors are needed. Ultrasound contrast agents can be used to develop new, more effective vectors for gene delivery. Ultrasound contrast agents lower the threshold for cavitation by ultrasound energy. Using physical properties of microbubbles and coating materials, genetic drugs have been incorporated into ultrasound contrast agents. Genebearing microbubbles can be injected IV and ultrasound energy applied to the target region. As the microbubbles enter the region of insonation, the microbubbles cavitate, locally releasing DNA. Cavitation also likely causes a local shockwave that improves cellular uptake of DNA. With transthoracic ultrasound, using commercially available diagnostic ultrasound system and an IV injection of gene‐bearing microbubbles, high levels of transgene expression are observed in the insonated region of the myocardium. This new technology using microbubbles and ultrasound for gene delivery merits further study and development.

Development of efficient plasmid DNA transfer into adult rat central nervous system using microbubble-enhanced ultrasound

“…However, extremely low transfection efficiency has limited its utility. 10,12 To overcome this problem, we focused on the application of ultrasound, as enhancement of transfection efficiency using ultrasound has been reported in various tissues such as cardiac muscle, 18 skeletal muscle, 19 carotid artery, 12 and the fetus. 13 Ultrasound-mediated plasmid DNA transfection enhances transfection efficiency, since ultrasound induces porosity of the cell membrane.…”

Gene Therapy Progress and Prospects: Nonviral vectors

“…It was modified with plasmid DNA before injection, followed by irradiation of ultrasound. At present, this technique is used for gene delivery to vascular cells, [22][23][24][25][26] muscle 26,27 and fetal mouse. 28 Hydrodynamic injection, a rapid injection of a large volume of naked DNA solution (eg 5 mg plasmid DNA injected in 5-8 s in 1.6 ml saline solution for a 20 g mouse) via the tail vein, can induce potent gene transfer in internal organs, especially the liver.…”

Ultrasound-contrast agent mediated naked gene delivery in the peritoneal cavity of adult rat

“…11,12 Ultrasonic exposure reversibly increases the cell membrane permeability by inducing transient acoustic cavitation to facilitate intracellular uptake of molecules. 13,14 Moreover, ultrasound can be focused specifically on a location where the target gene is to be delivered. Microbubbles, as the ultrasonic contrast agent, improve the efficiency of ultrasound-mediated gene transfection by lowering the threshold for cavitation initiated by ultrasound energy, 15 inducing transient pores in the cell membrane 16 and releasing genetic material such as plasmid DNA that has been pre-incorporated into microbubbles locally.…”