Ultrasound-based gene therapy uses 'microbubbles' to fight heart disease, cancer

By Mike Miliard
04:58 PM
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Pitt researchers say the new technique, which can introduce genetic material to cells without the side-effects that are now common, could soon be refined for use in clinical settings.

Researchers from University of Pittsburgh and UPMC say they're encouraged by what may one day be a new tool to help battle cancer and heart disease: an ultrasound-enabled genetic therapy called sonoporation.

A new report on this strategy, which involves using "microbubbles" to poke holes in cells to administer genes on a near molecular level, was published August 22 in the National Academy of Sciences.

Gene therapy often use viruses to gain cellular access – often causing severe side effects. Pitt and UMPC researchers are working instead to create these intravascular bubbles, which can be targeted to release their genetic "payloads" via focused ultrasound energy.

"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 Brandon Helfield, lead author of the study and a postdoctoral fellow at the Center for Ultrasound Molecular Imaging and Therapeutics at UPMC, in a statement.

"With a focused ultrasound beam, this approach lets us tune this delivery to the precise location of disease while sparing healthy tissue," he added. "Our study looks at some of the biophysics at play and helps us get closer to refining this technique as a clinical tool."

[Also: Big data, genomics, genetic engineering can combat rising healthcare costs, Ernst and Young says]

The Pitt researchers were able to do the work thanks to  a uniquely fast camera they developed that can reach speeds up to 25 million frames per second. With it, they were able to study the biophysics of sonoporation and determine that oscillating bubbles need to generate a minimum amount of localized shear stress – at which point cellular membranes perforate and allow the injection of a targeted therapeutic agent.

"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 Xucai Chen, research associate professor of medicine, Pitt Division of Cardiology, and Pittsburgh Heart, Lung and Blood Vascular Medicine Institute, who co-developed the camera system.

Helfield and Chen say their work, which was partly funded by the National Institutes of Health, will enable better understanding of how sonoporation works, and offer insights into how it can be tailored – whether through ultrasound amplitude levels or microbubble design – toward eventual clinical use.

New research will help "facilitate the intelligent design of treatment protocols and microbubble fabrication to preferentially cause the desired effect of opening nearby cells," Chen added. "It also gives us a starting point to investigate how cells cope with this treatment."

Flordeliza Villanueva, MD, director of the Center for Ultrasound Molecular Imaging and Therapeutics at Pitt and the senior author of the investigation, emphasized that it's essential to "understand the biophysical mechanisms of sonoporation in order to translate this approach into an effective gene or drug delivery tool for patients. 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."

Twitter: @MikeMiliardHITN
Email the writer: mike.miliard@himssmedia.com


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