Sunday, May 24, 2009

Gene-laden Bubbles Grow New Blood Vessels

Progress in human gene therapy -- the insertion of therapeutic DNA into tissues and cells in the human body -- has been slower than expected since the first clinical trials in 1990. One of the biggest challenges for this technology is finding ways to safely and effectively deliver genes only to the specific parts of the body that they are meant to treat.

Cardiologist Jonathan Lindner of Oregon Health and Science University will discuss his latest experiments in gene therapy, which use microscopic bubbles chemically modified to stick to the cells that line blood vessels.

This technique, ultrasound-mediated gene delivery (UMGD), exploits the properties of contrast agents, microparticles that are normally injected into the body to improve the quality of ultrasound images. In UMGD, the tiny particles are microbubbles composed of pockets of gas encapsulated by thin membranes that are coated with DNA before injection. A targeted pulse of ultrasound energy "rings" the bubbles like a bell, popping them in a specific location and releasing the DNA into the surrounding tissue.

To improve the specificity of this targeting, Lindner grafts long arm-like molecules to the outside of the bubbles. These arms, which do not interfere with the DNA attached to surface, are designed to recognize and bind to molecules on the outside of specific cells in the body, allowing the bubbles to attach to a tissue before being popped. In theory, this should improve both the specificity and efficiency of the gene therapy.

Lindner created an arm designed to attach to endothelial cells lining blood vessels. He will present data evaluating the behavior of these "targeted" bubbles in living tissue. The ability to stick these gene-laden microbubbles to the lining of blood vessels increased the amount of gene transfection. This strategy may be particularly important for delivering therapeutic DNA to the walls of blood vessels. For example, Dr. Lindner and collaborators have successfully stimulated the growth of new blood vessels using UMGD with microbubbles carrying a gene for vascular endothelial growth factor. This therapeutic use could be important for treating ischemia in patients who have had a heart attack, peripheral artery disease, or stroke.

The team is also investigating using the bubbles to transport small doses of drugs. "If you're trying to deliver a nasty drug to part of the body, this may be a way to improve safety," says Lindner.

The talk "Targeted microbubble technology and ultrasound-mediated gene delivery" by Jonathan Lindner will be presented at the 157th  Acoustical Society of America Meeting to be held May 18-22 in Portland, Ore.

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