A Controlled Study of Adenoviral-Vector–Mediated Gene Transfer in the Nasal Epithelium of Patients with Cystic Fibrosis

Abstract

In patients with cystic fibrosis, adenoviral-vector-mediated transfer of the CFTR gene did not correct functional defects in nasal epithelium, and local inflammatory responses limited the dose of adenovirus that could be administered to overcome the inefficiency of gene transfer.

The extra- and intracellular barriers to lipid and adenovirus-mediated pulmonary gene transfer in native sheep airway epithelium

“…The two most widely used gene transfer systems are cationic lipids and adenoviruses, with both assessed in phase I studies of nasal and pulmonary delivery. [1][2][3][4][5][6][7][8] Results have been encouraging, though only limited correction of the CF bioelectric defect has been observed. With respect to the extent of gene transfer needed, a present best estimate might be approximately 5% of normal cystic fibrosis transmembrane conductance regulator (CFTR) mRNA levels within every cell, 9 complete correction of the chloride defect in approximately 5% of cells within the airway epithelium, 10 or likely some combination of the two.…”

Effects of bronchopulmonary inflammation induced by Pseudomonas aeruginosa on adenovirus-mediated gene transfer to airway epithelial cells in mice

“…Recombinant adenoviruses have been used to transfer the gene encoding CFTR in vitro and in vivo, and clinical trials are in progress at several major CF centers in the USA. [5][6][7][8][9][10] Several potential barriers to successful adenovirus-mediated gene transfer to the airways have been recognized which include the need for repeated delivery to maintain transgene expression, 11 the host inflammatory response to the vector, and specific immune responses to adenovirus vectors. [12][13][14] In vivo models used so far to conduct published studies of adenovirus-mediated gene transfer to the lungs have employed animals with uninfected, uninflamed lungs at the time of vector administration.…”

Genetic engineering: Moral aspects and control of practice

“…In a recent controlled study in patients with cystic fibrosis, adenoviral vector-mediated transfer of the CFTR gene did not correct functional defects in the nasal epithelium. Furthermore, local inflammatory responses limited the dose of adenovirus that could be administered to overcome the inefficiency of gene transfer (37).…”