PHILADELPHIA Coating DNA with a topical steroid might make for more effective therapeutic gene delivery, according to bioengineers at the University of Pennsylvania. The researchers have shown that a common anti-inflammatory steroid, wrapped around a strand of DNA, can prevent the immune responses commonly associated with gene-transfer techniques.

Studies of the technique, performed in animal models, are presented in the Feb. 15 issue of the journal Gene Therapy, available online now.

"The steroid coating not only allows the gene to be taken up into a cell more easily, but the steroid itself also prevents the sort of inflammatory immune response seen in gene transfer therapy," said Scott Diamond, senior author and professor of bioengineering at Penn and associate director of Penn's Institute for Medicine and Engineering. "The concept paves the way to coupling therapeutic gene delivery with a pharamacological agent, an approach that mitigates some of the drawbacks to the gene-delivery techniques in use now."

Currently there are two basic approaches to delivering therapeutic genes: nonviral and viral. Injecting a subject with pure DNA is possible, but a DNA molecule, by itself, has inherent trouble in entering cells. Viral carriers can serve as delivery vehicles for DNA, literally infecting cells with new genes. Both methods, however, are associated with the creation of inflammatory immune responses that reduces the action of the therapeutic gene.

DNA is a large and negatively charged molecule, which is the source of the stumbling point in getting cells to take up DNA. To counter the negative charge of DNA, Diamond and his colleagues took a common steroid, dexamethasone, and made it "sticky" by adding a nitrogen-rich, postively charged tail. This tail provides the glue that attaches the steroid to the naked DNA.

"The steroid is a fatty lipid so, in essense, we have greased up DNA for cellular uptake," Diamond said,
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Contact: Greg Lester
glester@pobox.upenn.edu
215-573-6604
University of Pennsylvania
11-Feb-2004

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