The continued search for effective delivery methods for DNA-based gene therapies and vaccines has led some scientists to explore the idea of ultrasound. Scientists who have evaluated this technique have found that it possesses many attributes of an “ideal” transfer system for gene therapy. It is non-invasive, well-tolerated, and has a nearly flawless safety record over a wide range of frequencies and intensities. Not to mention, the original technology was invented in 1826 and the notion of ultrasound as a medical device has been around since the 1940’s; therefore, ultrasound is widely understood and accepted by the public. Last month, the NIH awarded researchers at Allegheny General Hospital (AGH) a $1.7 million grant to progress development of a nonviral gene therapy approach that uses ultrasound to deliver DNA directly to target cells. This approach to DNA delivery uses ultrasonic frequency sound waves to temporarily modify the permeability of the target cell’s membrane and allow DNA to enter the cell. First, a solution consisting of the gene construct and microbubbles are infused directly into the treatment site and are followed by the application of a low-frequency ultrasound beam to the same area. The bubbles vibrate and eventually implode. The resulting shockwave opens the cell’s membrane to allow the gene construct to enter. The therapy being evaluated by the AGH targets xerostomia – the irreparable damage to salivary glands causing dry mouth; as well as speech, chewing, and swallowing problems. These problems are often side effects caused by radiation therapies for head and neck cancer. The researchers will inject healthy gene constructs of the aquaporin-1 (AQP-1) fluid transporter gene into the saliva glands of pigs. They plan to move to human testing if the animal trials prove successful. Other potential candidates that have been identified for this type of delivery technique are Canavan disease, Hemophilia, and Celiac disease. If AGH sees positive outcome in their study over the next four years, ultrasound may be the next rising star in gene therapy delivery.