The role of dioleoyl phosphatidylethanolamine in cationic liposome mediated gene transfer. 1995

H Farhood, and N Serbina, and L Huang
Department of Pharmacology, University of Pittsburgh School of Medicine, PA 15261, USA.

In a reported gene assay, cationic liposomes containing the cationic lipid 3 beta-(N-(N',N'-dimethylaminoethane)carbamoyl)cholesterol (DC-Chol) and a neural phospholipid dioleoylphosphatidylethanolamine (DOPE) showed high transfection activity. DNA/liposome complex which contained low amount of liposomes could bind to the cell surface but failed to transfect the cells. We have designed a two-step protocol to examine this phenomenon in more detail. A431 human cells were incubated on ice (pulse) with DNA complexed to a low level of cationic liposomes. The cells were washed and incubated at 37 degrees C (chase) with or without free cationic liposomes of various composition (helper liposomes). Only liposomes enriched with DOPE showed helper activity; liposomes containing dioleoylphosphatidylcholine (DOPC), a structural analog of DOPE, had no helper activity. The delivery was inhibited by the lysosomotropic agent chloroquine and was optimal if the helper liposome chase was initiated immediately after the pulse. An endocytosis model of DNA delivery by cationic liposomes is proposed in which the principal function of the chase liposomes is to destabilize the endosome membrane and allow the release of DNA into the cytosol. This model is consistent with the known activity of DOPE to assume non-bilayer structures, hence destabilizing the endosome membrane.

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D008081 Liposomes Artificial, single or multilaminar vesicles (made from lecithins or other lipids) that are used for the delivery of a variety of biological molecules or molecular complexes to cells, for example, drug delivery and gene transfer. They are also used to study membranes and membrane proteins. Niosomes,Transferosomes,Ultradeformable Liposomes,Liposomes, Ultra-deformable,Liposome,Liposome, Ultra-deformable,Liposome, Ultradeformable,Liposomes, Ultra deformable,Liposomes, Ultradeformable,Niosome,Transferosome,Ultra-deformable Liposome,Ultra-deformable Liposomes,Ultradeformable Liposome
D010714 Phosphatidylethanolamines Derivatives of phosphatidic acids in which the phosphoric acid is bound in ester linkage to an ethanolamine moiety. Complete hydrolysis yields 1 mole of glycerol, phosphoric acid and ethanolamine and 2 moles of fatty acids. Cephalin,Cephalins,Ethanolamine Phosphoglyceride,Ethanolamine Phosphoglycerides,Ethanolamineglycerophospholipids,Phosphoglyceride, Ethanolamine,Phosphoglycerides, Ethanolamine
D010743 Phospholipids Lipids containing one or more phosphate groups, particularly those derived from either glycerol (phosphoglycerides see GLYCEROPHOSPHOLIPIDS) or sphingosine (SPHINGOLIPIDS). They are polar lipids that are of great importance for the structure and function of cell membranes and are the most abundant of membrane lipids, although not stored in large amounts in the system. Phosphatides,Phospholipid
D002412 Cations Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis. Cation
D002462 Cell Membrane The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells. Plasma Membrane,Cytoplasmic Membrane,Cell Membranes,Cytoplasmic Membranes,Membrane, Cell,Membrane, Cytoplasmic,Membrane, Plasma,Membranes, Cell,Membranes, Cytoplasmic,Membranes, Plasma,Plasma Membranes
D002738 Chloroquine The prototypical antimalarial agent with a mechanism that is not well understood. It has also been used to treat rheumatoid arthritis, systemic lupus erythematosus, and in the systemic therapy of amebic liver abscesses. Aralen,Arechine,Arequin,Chingamin,Chlorochin,Chloroquine Sulfate,Chloroquine Sulphate,Khingamin,Nivaquine,Sulfate, Chloroquine,Sulphate, Chloroquine
D004247 DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA, Double-Stranded,Deoxyribonucleic Acid,ds-DNA,DNA, Double Stranded,Double-Stranded DNA,ds DNA
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D014162 Transfection The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES. Transfections

Related Publications

H Farhood, and N Serbina, and L Huang
December 1995, Gene therapy,
H Farhood, and N Serbina, and L Huang
August 1996, Biophysical journal,
H Farhood, and N Serbina, and L Huang
May 1997, Human gene therapy,
H Farhood, and N Serbina, and L Huang
January 2000, Methods in molecular medicine,
H Farhood, and N Serbina, and L Huang
February 1995, Biochemical and biophysical research communications,
H Farhood, and N Serbina, and L Huang
November 1997, Biochimica et biophysica acta,
H Farhood, and N Serbina, and L Huang
April 1997, Sheng li ke xue jin zhan [Progress in physiology],
H Farhood, and N Serbina, and L Huang
September 2002, Journal of neurotrauma,
H Farhood, and N Serbina, and L Huang
September 1997, Human gene therapy,
Copied contents to your clipboard!