Direct transfer of the normal cystic fibrosis (CF) transmembrane conductance regulator (CFTR) gene to airway epitheiium was evaluated using a replicationdeficient recombinant adenovirus (Ad) vector containing normal human CFTR cDNA (Ad-CFTR). In vitro Ad-CFTR-infected CFPAC1 CF epitheiiai ceils expressed human CFTR mRNA and protein and demonstrated correction of defective CAMP-mediated CI-permeability. Two days after in vivo intratracheal introduction of Ad-CFTR in cotton rats, in situ analysis demonstrated human CFTR gene expression in lung epithelium. PCR amplification of reverse transcribed lung RNA demonstrated human CFTR transcripts derived from Ad-CFTR, and Northern analysis of lung RNA revealed human CFTR transcripts for up to 6 weeks. Human CFTR protefn was detected in epitheiial ceils using anti-human CFTR antibody 11-14 days after infection. While the safety and effectiveness remain to be demonstrated, these observations suggest the feasibility of in vivo CFTR gene transfer as therapy for the pulmonary manifestations of CF. introduction

The clinical manifestations of cystic fibrosis (CF), a common lethal recessive hereditary disorder, are dominated by abnormalities of the airway epitheiiai surface, including chronic mucus production, infection, and inflammation (Boat et al., 1989). The gene responsible for CF, termed the cystic fibrosis transmembrane conductance regulator (CFTR) gene, is localized on chromosome 7 at q31 (Rom-