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In blood vessel stents, innovative materials allow better control, delivery of gene therapy
Date:4/15/2008

e coating releases drugs meant to reduce vessel injury. Bare metal stents produce less inflammation, but without the benefit of drug delivery. Previously, in a proof-of-principle study in animals, Levys group attached to stents an extremely thin layer of protein, one molecule thick, containing adenovirus vectors that delivered genes that successfully inhibited restenosis. However, that method had serious limitations; it operated only within a narrow range of temperatures and acidity levels, and was useable only with adenovirus vectors.

The new formulation, said Levy, is more robust, more controllable and adaptable to any virus used as a gene therapy vector, not just adenoviruses. His team synthesized three components into a complex that tethers viral vectors to stent surfaces. One of the three components is an amplifier that increases the dose of gene vector more than fourfold over the previous formulation.

In addition, by varying another component, the stent can be tuned to release vector at a controlled rate that can theoretically be tailored to a schedule appropriate for the particular treatment. Prior studies have shown that 90 percent of the gene vector is released within 12 to 24 hours, after which vessel blockages regrow, said Levy. In this study, the stents had significant coverage of the vector seven days laterand less restenosis. Our goal is to customize the materials to allow peak release of the vector when it can have the maximum benefit.

The adenovirus vector carries genes that code for inducible nitric oxide synthase (iNOS), a protein that controls cell damage in blood vessels. In the current study, the iNOS reduced restenosis by 56 percent in the carotid arteries of treated rats, as compared with control animals.

Although this particular study used adenovirus vectors, said Levy, the synthetic formulation could tether any other type of viral gene therapy vector to the metal stents. It might also carry other therape
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Contact: John Ascenzi
Ascenzi@email.chop.edu
267-426-6055
Children's Hospital of Philadelphia
Source:Eurekalert

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