Sites of Uptake and Expression of Cationic Liposome/DNA Complexes Injected Intravenously

Publisher Summary This chapter presents an overview of the molecular mechanisms regulating the uptake and expression of DNA delivered by cationic liposomes. Although cationic-liposome-based DNA delivery systems are being used in clinical and preclinical gene-therapy protocols, little is known about the distribution and cellular uptake of cationic liposomes in vivo. The research described in this chapter focuses on the fate of systemically administered cationic liposomes and liposome/DNA complexes in mice. This chapter emphasizes on determining which cells within an animal are able to internalize liposomes and complexes after intravenous administration and to what extent uptake correlates with expression of plasmid reporter genes delivered by liposome complexes. Several strategies have been used to pursue the objectives of this research. Primarily fluorescent microscopy, both conventional and confocal, has been used. It is used to track the fate of fluorescently labeled liposomes and DNA after intravenous delivery in mice. Also, electron microscopy is used to examine the intracellular fate of gold-labeled liposomes. In addition, several different reporter genes have been used to measure expression from plasmid DNA delivered to various cellular sites. Yet, it is just the beginning stage of understanding the molecular mechanisms regulating the uptake and expression of DNA delivered by cationic liposomes.