1.1 General Background Regarding Cystic Fibrosis 
Cystic fibrosis (CF) is a recessive hereditary disorder caused by mutations 
of the cystic fibrosis transmembrane conductance regulator (CFTR) gene. It 
is the most common lethal hereditary disorder in the USA (Boat et al., 
1989). The disease is confined mostly to the Caucasian and hispanic popu- 
lation, although blacks and asians can be affected (Boat et al . , 1989; Tsui 
and Buchwald, 1991) . Parents of affected individuals have no clinical 
manifestations of CF. Males and females are equally at risk. In Caucasians, 
1 in 20 are heterozygotic carriers and the incidence is 1 in every 3000 
live births. In hispanics, the incidence is 1 in 7000 births. Each year, 
1,300 people are born in the U.S.A. with CF. There are an estimated 25,000 
individuals in the USA with CF, and approximately 50,000 worldwide (Cystic 
Fibrosis Foundation, Bethesda, Md. , personal communication) . 
The clinical manifestations of CF are primarily in the lung, intestinal 
tract, pancreas and liver (Boat et al., 1989; Welsh and Fick, 1987). The 
respiratory manifestations dominate, with thick mucus, chronic airway 
infections and inflammation beginning in early childhood and leading to 
progressive loss of lung function. Intestinal problems are most common in 
infants and include meconium ileus and intussusception. The exocrine glands 
of the pancreas are destroyed causing pancreatic enzyme deficiency and 
malnutrition. Diabetes can occur, as can liver failure. 
There is no cure for CF. The median survival in the USA is 29 years. Cur- 
rent treatments only ameliorate symptoms . Therapies involve administration 
of antibiotics, physical chest manipulations for bronchial drainage, physi- 
cal exercise, oral pancreatic enzymes, vitamins and dietary management. 
Lung transplantation has been carried out in CF individuals, but the effi- 
cacy of this procedure is not proven, and obtaining suitable donor organs 
is a major problem (Starnes et al. , 1992). 
The cost of this disease is significant. Beyond the personal tragedies for 
the affected individuals and their families, there are the associated costs 
of medical care. The average cost of drugs, diet supplements and medical 
equipment is $27,500 annually per patient. One to two hospital admissions 
per year are necessary for 38% of CF individuals. There are significant re- 
sources in the USA directed toward developing therapies for CF. In 1991, 
NIH directed $46.9 million to CF research and the National Cystic Fibrosis 
Foundation directed $24 million (Cystic Fibrosis Foundation, personal 
communication). In addition, approximately $30 million was spent by the 
pharmaceutical industry in trials directed toward therapy for CF (Cystic 
Fibrosis Foundation, 1991 statistics, personal communication). 
1.2 Pulmonary Manifestations of Cystic Fibrosis 
Inherent in the concept that the morbidity and mortality associated with CF 
might be reversed by transferring genes to epithelial cells of the lung is 
the knowledge that the clinical manifestations of CF are dominated by 
abnormalities manifest on the epithelial surface of the airways (Elborn and 
Shale, 1990). In this regard, while CF is also characterized by exor.rins 
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