Table of Contents 
Page 
I. Abstract 3 
I I . Background 
A. Cystic Fibrosis 3 - 5 
B. Preclinical studies 
1. Distribution of CFTR in Human Airway 6-7 
2. Production of recombinant CFTR adenoviruses 7 
3. Complementation of CF defect in vitro 7 - 8 
4. Xenograft model of human airway 8 - 9 
5. Safety and efficacy studies in human non-CF xenografts 9-11 
6. Complementation in human CF xenografts 11-12 
7. Safety studies in transgenic mice 1 2 
8. Safety and feasibility studies in nonhuman primates 12-13 
III. Experimental Design 
A. Patient selection 13-15 
B. Patient evaluation and selection 15-16 
C Clinical protocol 16-18 
D. Evaluation of therapy 18-19 
IV. Isolation and Production of CFTR Adenoviruses 
A. Vector construction 19-20 
B. Generation of recombinant Ad.CB-CFTR virus 2 1 
C Sequence analysis of recombinant virus 2 1 
D. Production of virus 2 2-23 
1 . Strategy and standard operating procedures 2 3 
2. Quality assurance and quality control 24-27 
V. Overall Assessment of Risks versus Benefits 
A. Risks to human subjects 2 7-2 9 
B. Risks to others 2 9-30 
C Potential Benefits 30-31 
VI . References 3 2-35 
VII. Informed Consent 3 6-42 
VIII. Responses to "Points to Consider" 43-59 
IX. Submission to IRB 6 0-70 
X. Appendix 7 1 
[808] Recombinant DNA Research, Volume 16 
