Stents Deliver Gene Therapy to Heart Vessels

Stents coated with a compound that binds in an extremely thin layer to bare metal surfaces could be used to deliver therapeutic genes to target cells in heart arteries.

Researchers at the children's hospital of Philadelphia (Philadelphia, PA, USA;) have developed a novel technique to attach therapeutic genes to a stent's bare metal surface. This technique could allow the genes to help heal the arteries surrounding the heart while avoiding the inflammation caused by polymer coatings. The study results were published in the December 2005 early edition of the Proceedings of the [U.S.] National Academy of Sciences.

The unique water-soluble compound, polyallylamine biphosphonate, binds to the stent's metal alloy surface in a layer with the thickness of only a single molecule. The biphosphonate holds and gradually releases adenovirus particles of the type used to deliver therapeutic genes. The researchers used a therapeutic gene that encodes inducible nitric oxide synthase (iNOS), a protein in the carotid artery, because of iNOS's ability to control cell damage in blood vessels.

In cell cultures, the adenovirus successfully delivered genes from alloy samples to animal arterial smooth muscle cells. In a second experiment using rodents, the researchers detected gene expression with significantly lower restenosis in the carotid arteries of animals with the experimental stents, compared to control animals with conventional, polymer-coated stents.

"This is the first study to demonstrate successful delivery of a gene vector from a bare metal surface,” said senior author Dr. Robert J. Levy, the William J. Rashkind chair of pediatric cardiology at the children's hospital of Philadelphia. "However, in further studies, one might use a combination of therapeutic genes or different gene vectors, for even better results.”