Journal of Applied Physiology, Vol 77, Issue 1 415-419, Copyright © 1994 by American Physiological Society

ARTICLES

No lung toxicity after repeated aerosol or intravenous delivery of plasmid-cationic liposome complexes

A. E. Canonico, J. D. Plitman, J. T. Conary, B. O. Meyrick and K. L. Brigham
Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.

The safety aspects of human gene therapy are of paramount importance in developing an ideal system for gene transfer. Lipofection using DNA in the form of a plasmid has been shown to successfully transfect the lungs when administered either intravenously or by aerosol. We have shown that repeated intravenous or aerosol administration of a plasmid containing the recombinant human alpha 1-antitrypsin gene and a cytomegalovirus promoter complexed to cationic liposomes results in no adverse effects on pulmonary histology, lung compliance, lung resistance, or alveolar-arterial oxygen gradient. Immunohistochemistry and Western blot analysis confirm successful gene transfer using this delivery system. We conclude that plasmids complexed to cationic liposomes may be a safe and efficacious delivery system for in vivo gene transfer to the lungs. Using this delivery system, in vivo gene therapy to the lungs can be achieved by either intravenous or aerosol administration of the transgene.

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