Lung-specific direct in-vivo gene transfer with recombinant plasmid
dna.
Tsan, Min-Fu, Julie E. White, and Barbara Shepard.
Research Service, Samuel S. Stratton Department of Veterans Affairs
Medical Center, and Departments of Physiology and Medicine, Albany
Medical College, Albany, NY 12208; and Wadsworth Center for
Laboratory and Research, New York State Department of Health, Albany,
NY 12201
APStracts 2:0038L, 1995.
A number of gene delivery methods have been developed to facilitate
gene transfer into mammalian somatic cells in-vivo. In this study, we
demonstrated that tracheal insufflation of 2 recombinant plasmids
containing a bacterial gene, chloramphenicol acetyltransferase (CAT),
driven by the cytomegalovirus (CMV) immediate early
promoter/enhancer, either alone or complexed to cationic liposomes,
resulted in efficient and selective transfection of the lungs in
rats. When the Simian virus 40 (SV40) promoter/enhancer was used,
there was no detectable transfection. Insufflation of plasmid DNA was
as efficient as plasmid/liposome complexes in transfecting the lungs.
Expression of CAT gene in the lungs was noted as early as 1 day after
insufflation of plasmid DNA alone or plasmid/liposome complexes, and
lasted for >21 days. In contrast, intravenous injection of plasmid
alone or plasmid/liposome complexes did not result in transfection of
the lungs. Because of its simplicity without the potential adverse
effect of any gene delivery systems, intratracheal delivery of
recombinant plasmid DNA may have potential implication for lung
-specific gene therapy.
Received 20 October 1994; accepted in final form 24 March 1995.
APS Manuscript Number L302-4.
Article publication pending Am. J. Physiol. (Lung Cell. Mol.
Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 21 March 1995