Bubbles Oust Viruses in Therapy

May. 28, 2003
By Erik Baard

Dutch researchers say they've demonstrated a way to use sound waves to manipulate microscopic bubbles so that they can deliver DNA and other molecules, such as drugs, into cells.

The goal is to reduce geneticists' reliance on viruses to deliver genes into cells, a method that has led to cancers in some patients, said University of Twente physicist Claus-Dieter Ohl.


While innovative drug and gene therapies have been developed in recent years, researchers are still looking for efficient and safe ways to deliver the therapeutic molecules into cells.

Experiments haven't been performed in human bodies yet. But using Ohl's method, a solution of DNA and microscopic bubbles would be injected into a patient's bloodstream. Ultrasonic waves would then cause the bubbles to compress. The compressed bubbles act like tiny syringes that shoot jets of DNA or drugs past the cell membrane.

Ohl said the process would be much like clapping your hands while they are partly below the water's surface. Strong jets shoot in the direction of the channel made by your hands.

Injecting microbubbles into the bloodstream is nothing new -- it's a common technique in ultrasound imaging now, where the microbubbles are used as tracers. In this process, the bubbles would function as carriers to deliver molecules into the cell.

In experiments, Ohl's jets reach 200 meters per second, enough to blast through a cell membrane. That should increase with perfection of the technique, which will be described in a coming issue of Physical Review Letters, Ohl said. The ultrasound levels needed to compress the bubbles are no greater than those already in use today.

The technique has been tried on laboratory animals. In an experiment performed by Professor Katsuro Tachibana of Fukuoka University School of Medecine, Japan, a gene for extra fingers was injected into a chicken embryo, which later developed an additional digit. The study was published in the May 8 edition of Nature.

The gene delivery involves a temporary rupture of the cell membrane to allow the entry of DNA. At the university of Twente, direct microscopic observation of the a cell membrane rupture by a gently oscillating bubble was performed (see pictures 1 and 2) by physicist Philippe Marmottant and Sascha Hilgenfeldt.

The approach is one of the latest scientists have used in an attempt to replace viruses as a delivery mechanism. Just this week, researchers at Oak Ridge National Laboratory announced a way to ferry genes into cells using carbon nanofibers.

But lessening gene therapy's reliance on viral vectors won't be easy, said Dr. Mark Kay, a professor of pediatrics and genetics at the Stanford University School of Medicine.

"A lot (of) ideas show promise in tissue culture cells, but cause problems in vivo (in living beings)," Kay said. "But anything that can work and get rid some of the disadvantages of current vectors is good."

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