1. Introduction 
This protocol represents an initial evaluation of the safety and biologic 
efficacy of the administration of replication deficient recombinant adeno- 
virus containing the human CFTR cDNA to the respiratory epithelium of 
adults with cystic fibrosis (CF) . The protocol is divided into seven sec- 
tions and 4 appendices, as follows: 
Section 1: Provides general background regarding CF, with primary 
focus on the pulmonary manifestations and current therapy for the 
disorder, the rationale for gene therapy to treat the respiratory 
manifestations of CF, the CFTR gene and its mutations, the CFTR pro- 
tein and its functions, the molecular pathogenesis of CF, the cell 
targets for gene transfer in CF, CFTR gene expression in the airway 
epithelium, pathogenesis of the respiratory manifestations of CF, and 
the rationale for a recombinant adenovirus as the vector of choice. 
Section 2: Presents an overview of the adenovirus and details of the 
fabrication, production, structure, formulation and quality control 
parameters of the replication deficient recombinant vector containing 
the human CFTR cDNA. 
Section 3: Details the in vitro and in vivo experimental evidence 
supporting the use of a replication deficient recombinant adenovirus 
containing the human CFTR cDNA to treat the respiratory manifestations 
of CF. 
Section 4: Summerizes the safety concerns and presents the in vitro 
and in vivo safety studies in cotton rats and non-human primates 
regarding the use of a replication deficient recombinant adenovirus 
containing the human CFTR cDNA. 
Section 5: Presents the general design of the human protocol, con- 
straints that dictate design of the protocol, relevant baseline safety 
data from individuals with CF, criteria for patient eligibility and 
selection safety parameters to be examined, efficacy parameters to be 
evaluated, details of the clinical protocol, safety issues for health 
care workers and the environment, risk-benefit considerations for the 
patient, plans for doing long term patient follow up, clinical facili- 
ties for the study, privacy and confidentiality, informed consent, re- 
porting of serious adverse affects, and future directions. 
Section 6: Protocol in the NIH Recombinant Advisory Committee "Points 
to Consider" format. 
Section 7: References 
Appendix 1: Copy of Rosenfeld, MA et al Cell 1992; 68:143-155 
Appendix 2: Copy of Mastrangeli, A et al J Clin Invest 1992 (in press) 
Appendix 3: Sequence data 
Appendix 4: Approval documents 
Recombinant DNA Research, Volume 16 
