Gene Therapy for CF

Article excerpt

New research on gene replacement therapy offers the hope of a cure for cystic fibrosis (CF). This fatal disease, symptomized by coughing, wheezing, lung infections, very salty sweat, and excessive appetite with inability to gain weight, affects about 30,000 Americans.

CF manifests when a person receives a mutated copy of the CFTR gene from both parents. More than 10 million people carry one copy of the defective gene. Most CF patients die in childhood, but some live into their 30s or 40s. Advances in drug therapies and other treatments such as lung transplants have improved the quality of life of CF patients in recent years, but still do not offer a cure.

Because lung infections are responsible for most CF fatalities, research into gene therapy for treating the disease has initially focused on replacing the mutant genes in the epithelial cells lining the lungs and nasal passages. But the human body has evolved a complex system to prevent invasion of foreign DNA, and the lungs have a particularly strong defense system. So scientists need to find a way to "trick" the cells into accepting replacement genes. In a report in the June 2000 issue of Nature Biotechnology, Silvia M. Kreda, a clinical research associate of medicine at the University of North Carolina at Chapel Hill, and colleagues describe research with a particular type of airway receptor molecule that may offer a reliable pathway into cells.

Instead of producing the normal protein that forms channels in cell membranes for the passage of salt out of cells, people with CF produce a faulty protein, which causes a thick mucus that impairs function of the lungs, intestines, and other organs. If healthy genes can be transferred into the CF patient's cells, theoretically they should produce the protein product necessary to form the channels for proper electrolyte transport out of the airway cells.

Kreda and colleagues identified the P2[Y.sub.2] molecule receptor on the membrane surface of the lungs as a potential target for shuttling healthy genes into the airway passages. Their research strategy was to combine the nucleotide UTP, which binds to certain receptor molecules on the outside of the epithelial cells, with a commonly used vector known as an adenovirus. …