Study shows receptor molecule facilitates introduction of corrected genes ...( Medical researchers trying to perfect...)

Medical researchers trying to perfect gene therapy face a major obstacle in inserting corrected genes into cell nuclei where they can direct production of healthy proteins that the defective cellular machinery cannot make.

In the past, scientists have used weakened viruses as vectors to carry working genes into cells, but so far the body's sophisticated natural defenses against invaders -- especially in the lung -- have limited their effectiveness.

Now, University of North Carolina at Chapel Hill School of Medicine scientists have found what they think could be a big improvement. For the first time, they have targeted a special class of receptor molecules on the surfaces of airway cells. Their experiments show that when activated, a G-protein-coupled receptor can work like a revolving door allowing weakened viruses into cells, along with their attached therapeutic payload.

A report on the research appears in the June issue of Nature Biotechnology. Authors are Drs. Silvia M. Kreda, Raymond J. Pickles and Eduardo R. Lazarowski, all research associates in medicine, and Dr. Richard C. Boucher, Kenan professor of medicine.

"We linked an adenovirus vector to a small signaling molecule known as UTP that interacts with the receptor, and we obtained specific gene transfer in human airway cells," Kreda said. "This strategy is flexible and conceptually could allow us to successfully correct other cell types or use different gene therapy vectors."

Boucher, director of UNC-CH's Cystic Fibrosis Center, likened vectors to mail delivery trucks moving valuable cargo. He also called the strategy "the classic Trojan Horse approach" because it tricks the mostly impenetrable cell surfaces. Their success sets the stage for developing a system with clinical applications.

"You have to make the virus look like something else that can attach to airway cells and have the capacity to penetrate inside," he said. "Dr. Kreda's paper shows there actually are these rec
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Contact: David Williamson
david_williamson@unc.edu
919-962-8596
University of North Carolina at Chapel Hill
28-May-2000