Based on the constraints inherent in the disease and the vector system, and 
the need to maximize safety and gain access to biologic specimens to demon- 
strate biologic efficacy, the following are the inclusion and exclusion 
criteria for the study population. Patients with cystic fibrosis meeting these 
criteria will be chosen from among patients participating in ongoing Pulmonary 
Branch, NHLBI studies and those referred to the Pulmonary Branch. 
5.4.1 Inclusion criteria 
Males or females 21 years or older 
Cystic fibrosis defined by routine clinical criteria, a positive sweat 
chloride test, a genotype of the "delta F508" mutation on both CFTR alleles or 
a compound heterozygote of the type "delta F508-null", with the null mutation 
of a type known not to produce CFTR mRNA (see below) . 
Documented sterility in males (semen analysis) and females (documentation of 
absence of uterus and/or ovaries) 
Lung disease typical of CF, with FEV1 > 1.2 L/sec 
Shwachman score 40-70 (mild to moderate disease) (Shwachman and Kulczycki, 
1958). If there is gastrointestinal or liver disease present, it must be mild 
and stable with appropriate therapy 
If diabetes mellitus is present, it must be stable, with no history of 
diabetic ketoacidosis, hyperosmolar coma or hypoglycemia requiring 
hospitalization within the previous three years 
Demonstrated ability in the baseline period to undergo nasal brushing once 
weekly without complications 
Demonstrated ability in the baseline period to undergo fiberoptic bronchoscopy 
with brushing of the large airways and bronchoalveolar lavage once monthly 
without complications 
Reproducible respiratory epithelial potential difference (to subcutaneous 
tissues) of > -40 mV and/or airway epithelium unable to secrete Cl - in a 
normal fashion in response to cAMP 
Airway epithelial CFTR mRNA demonstration of CFTR mutations of the type "delta 
F508 homozygote" or a compound heterozygote "delta F508-null" 
No detectable CFTR protein in airway epithelium (using methods described in 
Section 3.1.2) 
Not taking experimental medications relevant to lung disease of CF for at 
least 4 weeks prior to entry into study, including recombinant human DNase, 
anti-proteases such as alpha 1-antitrypsin or recombinant secretory 
leukoprotease inhibitor, or amiloride 
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