Nature Biotechnology
15, 167 - 173 (1997)
doi:10.1038/nbt0297-167
Factors influencing the efficiency of cationic liposome-mediated intravenous gene deliveryYong Liu1, 4, Leslie C. Mounkes1, 4, H. Denny Liggitt2, Carolyn S. Brown3, Igor Solodin3, Timothy D. Heath3
& Robert J. Debs1, *
1California Pacific Medical Research Institute, 2330 Clay St., San Francisco, CA 94115;
2Department of Comparative Medicine, University of Washington, Seattle, WA 98195;
3School of Pharmacy, University of Wisconsin-Madison, WI53706.
4Authors contributed equally.
*(e-mail: karin@itsa.ucsf.edu). We have characterized the relationships between the design of cationic liposomes as a gene transfer vehicle, their resulting biodistribution and processing in animals, and the level and sites of gene expression they produce. By redesigning conventional cationic liposomes, incorporating cholesterol (chol) as the neutral lipid and preparing them as multilamellar vesicles (MLV), we increased the efficiency of cationic liposome:DNA complex (CLDC)-mediated gene delivery. Expression of the luciferase gene increased up to 1,740-fold and of the human granulocyte-colony stimulating factor (hG-CSF) gene up to 569-fold due to prolonged circulation time of injected CLDC, and increased uptake and retention in tissues. The level of gene expression per microgram of DMA taken up per tissue was 1,000-fold higher in lung than in liver, indicating that in addition to issues of delivery and retention of injected DNA, tissue-specific host factors also play a central role in determining the efficiency of expression. Vascular endothelial cells, monocytes, and macrophages are the cell types most commonly transfected by intravenous injection of CLDC.
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