Efficient gene transfer to airway epithelium using recombinant Sendai virus

Clinical studies of gene therapy for cystic fibrosis (CF) suggest that the key problem is the efficiency of gene transfer to the airway epithelium. Th e availability of relevant vector receptors, the transient contact time bet ween vector and epithelium, and the barrier function of airway mucus contri bute significantly to this problem. We have recently developed recombinant Sendai Virus (SeV) as a new gene transfer agent. Here we show that SeV prod uces efficient transfection throughout the respiratory tract of both mice a nd ferrets in vivo, as well as in freshly obtained human nasal epithelial c ells in vitro. Gene transfer efficiency was several log orders greater than with cationic liposomes or adenovirus. Even very brief contact time was su fficient to produce this effect, and levels of expression were not signific antly reduced by airway mucus. Our investigations suggest that SeV may prov ide a useful new vector for airway gene transfer.