Novel Gene Therapy Technique Improves Targeted Drug Delivery

Gene therapy administered through ultrasound could potentially create targeted approaches to fight common diseases, such as heart disease and cancer, a recent study found.

The researchers used a novel method called sonoporation, which combines ultrasound and microbubbles to poke holes in cells, according to a study published by the Proceedings of the National Academy of Sciences.

“We can use ultrasound energy in combination with small, gas-filled bubbles to selectively open up cells to allow the delivery of therapeutic agents," said lead study author Brandon Helfield, PhD. “With a focused ultrasound beam, this approach lets us tune this delivery to the precise location of disease while sparing healthy tissue. Our study looks at some of the biophysics at play and helps us get closer to refining this technique as a clinical tool.”

The current method for gene therapy consists of using viruses to access the inside of cells. This method can cause side-effects, such as immune system reactions. Researchers created gene-loaded intravascular microbubbles that can be targeted to release their contents through focused ultrasound energy, according to the study.

Researchers also created an ultrafast imaging camera to examine the biophysics of sonoporation. Through the use of the camera, researchers were able to determine that the oscillating bubbles need to generate a minimum amount of localized shear stress to allow the entry of a targeted drug, according to the study.

“By allowing us to actually see the microbubbles vibrating at millions of times per second, our unique camera enabled us to determine that microbubble-induced shear stress is the critical factor for sonoporation,” said researcher Xucai Chen, PhD. “This new information, in turn, will facilitate the intelligent design of treatment protocols and microbubble fabrication to preferentially cause the desired effect of opening nearby cells. It also gives us a starting point to investigate how cells cope with this treatment.”

Researchers believe that their findings will lead to a more tailored approach that can be used in a clinical setting.

“It's critical for us to understand the biophysical mechanisms of sonoporation in order to translate this approach into an effective gene or drug delivery tool for patients,” said senior author of the study Flordeliza Villanueva, MD. "Building on the PNAS study, we are continuing to investigate how sonoporation affects the function of treated cells and to develop strategies to maximize its therapeutic effects."