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Ultrastructural Morphology of Cationic Liposome/Dna Complexes for Gene Therapy: Correlation to Transfection Activity

Published online by Cambridge University Press:  02 July 2020

Brigitte Sternberg ,
Keelung Hong ,
Weiwen Zheng  and
Demetrios Papahadjopoulos
Brigitte Sternberg
Affiliation:
California Pacific Medical Center, Research Institute, San Francisco, California, 94115, USA.
Keelung Hong
Affiliation:
California Pacific Medical Center, Research Institute, San Francisco, California, 94115, USA.
Weiwen Zheng
Affiliation:
California Pacific Medical Center, Research Institute, San Francisco, California, 94115, USA.
Demetrios Papahadjopoulos
Affiliation:
California Pacific Medical Center, Research Institute, San Francisco, California, 94115, USA.
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Extract

Complexes formed during interaction of cationic liposomes with poly-nucleotides such as DNA (CLDC) display a variety of polymorphic and metastable structures. These include multilamellar structures of alternating lipid bilayers and DNA monolayers; fibrillar structures, among them spaghetti-liketubules (Figure 1), and map-pin-structures(Figure 2), and, finally, non-bilayer lipid arrangements, such as hexagonal (HII) (Figure 3) and cubic phases.

In order to find out the “active” structure(s) in terms of transfection, we investigated the transfection activity both in vivoand in vitroof CLDC composed of the lipid DDAB (dimethyl-dioctadecylammonium bromide) and Choi (cholesterol) or DOPE (l,2-dioleoyl-sn-glycerol-3- phosphoethanolamine) as helper lipids. In parallel we studied their morphology by freeze-fracture electron microscopy.The in vivostudies were carried out in mice following i.v. injection and therefore the morphology of the CLDC was investigated in mouse serum.

Type
Biomedical Applications
Information
Microscopy and Microanalysis , Volume 5 , Issue S2: Proceedings: Microscopy & Microanalysis '99, Microscopy Society of America 57th Annual Meeting, Microbeam Analysis Society 33rd Annual Meeting, Portland, Oregon August 1-5, 1999 , August 1999 , pp. 1108 - 1109
Copyright
Copyright © Microscopy Society of America

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