Gene delivery to the lung using protein/ polyethylenimine/plasmid complexes

• Published in: Gene therapy Vol. 9; no. 7; pp. 463 - 471
• Main Authors: ORSON, F. M, SONG, L, GAUTAM, A, DENSMORE, C. L, BHOGAL, B. S, KINSEY, B. M
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01.04.2002
• Subjects: Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Applied cell therapy and gene therapy; Biological and medical sciences; Biotechnology; Deoxyribonucleic acid; DNA; Female; Fundamental and applied biological sciences. Psychology; Gene Expression; Gene therapy; Gene transfer; Genetic Therapy - methods; Genetic Vectors - administration & dosage; Health. Pharmaceutical industry; Humans; Industrial applications and implications. Economical aspects; Injections, Intravenous; Intravenous administration; Luciferases - genetics; Lung cancer; Lung Diseases - therapy; Male; Medical sciences; Mice; Mice, Inbred BALB C; Plasmids; Polyethyleneimine; Reporter gene; Serum Albumin - genetics; Time Factors; Tissue Distribution; Transfection - methods; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Plasmid; Vertebrata; Mammalia; Intravenous administration; Mouse; Lung; Rodentia; Albumin; Gene therapy; Vector; Polyethylene imine; Genetic transfer
• ISSN: 0969-7128; 1476-5462
• DOI: 10.1038/sj.gt.3301666

Delivery of genes to the lung has enormous potential in a wide variety of illnesses, from lung cancer to genetic deficiency diseases. Many delivery systems have been utilized, each with its own advantages and limitations. Polyethylenimine is a polycation capable of binding and compacting DNA, enabling intravascular plasmid delivery to normal tissues in such a way that the plasmid can be expressed in a proportion of the exposed cells. We have developed a novel intravenous method to deliver small amounts of plasmid to lung tissue, using nontoxic quantities of polyethylenimine in combination with albumin (or other soluble proteins). Injection of 1 microg or less of plasmid resulted in highly efficient gene expression in lung interstitial and endothelial tissues (0.5 to 1 ng luciferase per microg plasmid DNA), while larger quantities of plasmid reduced relative gene expression. Using luciferase as a reporter gene, single injections had maximal gene expression between 24 and 48 h, with a rapid decline thereafter. In contrast to some other delivery systems, however, no inhibition of gene expression occurred during multiple rounds of plasmid administration through 20 days. As a result, this method may have useful applications in diseases that could benefit from recurrent therapeutic gene delivery.