Gene delivery to the lung using protein/polyethylenimine/plasmid complexes.
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.
Orson
F M
FM
Veterans Affairs Medical Center, Baylor College of Medicine, Houston, TX, USA.
Song
L
L
Gautam
A
A
Densmore
C L
CL
Bhogal
B S
BS
Kinsey
B M
BM
D000818:Animals; D005260:Female; D015870:Gene Expression; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage; D006801:Humans; D007275:Injections, Intravenous; D008156:Luciferases / Q000235:genetics; D008171:Lung Diseases / Q000628:therapy*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D011094:Polyethyleneimine; D012709:Serum Albumin / Q000235:genetics*; D013997:Time Factors; D014018:Tissue Distribution; D014162:Transfection / Q000379:methods
D012709:Serum Albumin; D011094:Polyethyleneimine; D008156:Luciferases