Cationic liposome-DNA complexes: from liquid crystal science to gene delivery applications.
At present, there is an unprecedented level of interest in the properties and structures of complexes consisting of DNA mixed with oppositely charged cationic liposomes (CLs). The interest arises because the complexes mimic natural viruses as chemical carriers of DNA into cells in worldwide human gene therapy clinical trials. However, since our understanding of the mechanisms of action of CL-DNA complexes interacting with cells remains poor, significant additional insights and discoveries will be required before the development of efficient chemical carriers suitable for long-term therapeutic applications. Recent studies describe synchrotron X-ray diffraction, which has revealed the liquid crystalline nature of CL-DNA complexes, and three-dimensional laser-scanning confocal microscopy, which reveals CL-DNA pathways and interactions with cells. The importance of the liquid crystalline structures in biological function is revealed in the application of these modern techniques in combination with functional transfection efficiency measurements, which shows that the mechanism of gene release from complexes in the cell cytoplasm is dependent on their precise liquid crystalline nature and the physical and chemical parameters (for example, the membrane charge density) of the complexes. In [section sign] 5, we describe some recent new results aimed at developing bionanotube vectors for gene delivery.
Safinya
Cyrus R
CR
Department of Materials, Biomolecular Science and Engineering Programme, University of California, Santa Barbara, CA 93106, USA. safinya@mrl.ucsb.edu
Ewert
Kai
K
Ahmad
Ayesha
A
Evans
Heather M
HM
Raviv
Uri
U
Needleman
Daniel J
DJ
Lin
Alison J
AJ
Slack
Nelle L
NL
George
Cyril
C
Samuel
Charles E
CE
D002412:Cations; D004247:DNA / Q000008:administration & dosage / Q000737:chemistry* / Q000235:genetics; D016503:Drug Delivery Systems; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D066298:In Vitro Techniques; D008081:Liposomes; D050866:Liquid Crystals; D046911:Macromolecular Substances; D018613:Microscopy, Confocal; D008954:Models, Biological; D008958:Models, Molecular; D043942:Nanotubes; D017356:Synchrotrons; D014162:Transfection; D014961:X-Ray Diffraction
D002412:Cations; D008081:Liposomes; D046911:Macromolecular Substances; D004247:DNA