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(Received for publication, July 31, 1996, and in revised form, October 31, 1996)
From the Howard Hughes Medical Institute, Departments of Internal
Medicine and Physiology and Biophysics, University of Iowa College
of Medicine, Iowa City, Iowa 52242
Improving the efficiency of gene transfer remains
an important goal in developing new treatments for cystic fibrosis and
other diseases. Adenovirus vectors and nonviral vectors each have
specific advantages, but they also have limitations. Adenovirus vectors efficiently escape from the endosome and enter the nucleus, but the
virus shows limited binding to airway epithelia. Nonviral cationic
vectors bind efficiently to the negatively charged cell surface, but
they do not catalyze subsequent steps in gene transfer. To take
advantage of the unique features of the two different vector systems,
we noncovalently complexed cationic molecules with recombinant
adenovirus encoding a transgene. Complexes of cationic polymers and
cationic lipids with adenovirus increased adenovirus uptake and
transgene expression in cells that were inefficiently infected by
adenovirus alone. Infection by both complexes was independent of
adenovirus fiber and its receptor and occurred via a different cellular
pathway than adenovirus alone. Complexes of cationic molecules and
adenovirus also enhanced gene transfer to differentiated human airway
epithelia in vitro and to the nasal epithelium of cystic
fibrosis mice in vivo. These data show that complexes of
adenovirus and cationic molecules increase the efficiency of gene
transfer, which may enhance the development of gene therapy.
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