ADENOVIRUS-MEDIATED TRANSFER OF THE CFTR GENE TO LUNG OF NONHUMAN-PRIMATES - BIOLOGICAL EFFICACY STUDY

We have evaluated the biological efficacy of E1-deleted adenoviruses i n baboons for lung-directed gene therapy of cystic fibrosis (CF). The experimental design attempted to simulate a phase I clinical trial wit h animals receiving a single dose of virus to an isolated pulmonary se gment. A total of 14 animals divided into four groups, each of which r eceived escalating doses of virus, were used. Individual animals were necropsied 4 and 21 days after gene transfer and tissues were carefull y surveyed for gene expression. Expression of the transgene was locali zed primarily to the area into which it was infused; the efficiency of recombinant gene expression and the abundance of transgene sequences were proportional to dose and both diminished with time. Transgene exp ression was found predominantly in alveolar cells with patches of expr ession in the proximal and distal airway. Analysis of adenoviral prote in expression within transgene-expressing cells revealed infrequent ex pression of the E2a gene and no detectable expression of late genes (i .e., fiber protein). These results suggest that recombinant adenovirus can be used to transfer genes efficiently to the lung of nonhuman pri mates and that therapeutic strategies of cystic fibrosis may require r epetitive administration with current vectors.