¹Inex Pharmaceuticals Corporation, Burnaby, Canada

²Institute for Molekularbiologie und Tumorforschung, Marburg, Germany

³Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, Canada

Correspondence to: P Tam, Inex Pharmaceuticals Corporation, 100 - 8900 Glenlyon Parkway, Burnaby, BC V5J 5J8, Canada

^aThese authors contributed equally to this work.

the structure of 'stabilized plasmid-lipid particles' (splp) and their properties as systemic gene therapy vectors has been investigated. we show that splp can be visualized employing cryo-electron microscopy to be homogeneous particles of diameter 72 ± 5 nm consisting of a lipid bilayer surrounding a core of plasmid dna. it is also shown that splp exhibit long circulation lifetimes (circulation half-life >6 h) following intravenous (i.v.) injection in a murine tumor model resulting in accumulation of up to 3% of the total injected dose and concomitant reporter gene expression at a distal (hind flank) tumor site. In contrast, i.v. injection of naked plasmid DNA or plasmid DNA-cationic liposome complexes did not result in significant plasmid delivery to the tumor site or gene expression at that site. Furthermore, it is shown that high doses of SPLP corresponding to 175 g plasmid per mouse are nontoxic as assayed by monitoring serum enzyme levels, whereas i.v. injection of complexes give rise to significant toxicity at dose levels above 20 g plasmid per mouse. It is concluded that SPLP exhibit properties consistent with potential utility as a nontoxic systemic gene therapy vector. Gene Therapy (2000) 7, 1867-1874.

liposomes; cancer gene therapy; intravenous gene therapy; tumour transfection