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UIC News Tips
University of Illinois at Chicago Office of Public Affairs (MC 288)
601 S. Morgan St., Chicago, IL 60607-7113, (312) 996-3456, www.uic.edu/depts/paff

September 20, 2001 Contact: Sharon Butler (312) 355-2522; sbutler@uic.edu

A vector that targets blood vessels in the lung

Gene therapy — replacing ailing genes with healthy ones — holds great promise as a cure for diseases ranging from pulmonary hypertension to Alzheimer's.

The problem is finding a carrier that, like the homing pigeon, knows exactly where to deliver its genetic message. Researchers believe that viruses might work as carriers, or vectors, because, by nature's design, viruses can wiggle their way into the nuclei of our cells, inserting their own cargo of DNA. But viruses attack the whole body, not just specific tissues.

"It's a problem of addressing," said Sergei Danilov, assistant professor in the department of anesthesiology at the University of Illinois at Chicago College of Medicine.

Now, Danilov's UIC team and collaborating scientists at the Gene Therapy Center at the University of Alabama have found an effective way to deliver genes specifically to the lung. The research findings are reported in the September issue of Nature Biotechnology.

"Of course, much more research remains to be done," said Danilov. "But our results demonstrate for the first time an effective and selective gene delivery system that may one day be useful in gene therapy for the treatment of lung diseases."

The virus that Danilov and his colleagues modified, called an adenovirus, has long been recognized as a potential vector because it is efficient at making its way into cell nuclei. But studies in rodents and primates showed that adenoviruses do not land up in the lung when injected into blood vessels. Instead, they have a natural affinity for the liver, whose cells have the required receptors.

Danilov's team created a monoclonal antibody to angiotensin-converting enzyme, which regulates blood vessel tone and localizes largely in the lung's blood vessels. By coating the virus with this antibody, they were able to make the virus accumulate in the lungs of experimental rats. Moreover, by blocking certain receptors on the surface of the adenovirus, the researchers could prevent large numbers from ending up in the liver.

"This technique enabled us to get high concentrations of the gene into the lungs while simultaneously decreasing concentrations in other parts of the body," said Danilov.

In subsequent work, the researchers also added a promoter, a piece of DNA that activates gene expression —- in this case, the gene that lights the firefly, which was inserted in the virus for measurement purposes. The promoter works specifically in lung tissue.

With the addition of the lung-specific promoter, the scientists were able to achieve a 300,000-fold increase in the relative concentrations of the firefly gene in the lung as opposed to the liver. In gene therapy, a therapeutic gene would replace the firefly gene.

- UIC -

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