Cationic Liposomes for Gene Delivery: Novel Cationic Lipids and Enhancement by Proteins and Peptides

Abstract

Cationic liposome-DNA complexes, also called "lipoplexes", constitute a potentially viable alternative to viral vectors for the delivery of therapeutic genes. Here we review the mechanisms of lipoplex-mediated gene delivery, the barriers to efficient gene expression, and novel cationic lipids used for transfection. We also describe methods for enhancing gene transfer via the use of proteins, including transferrin, albumin and asialofetuin, and synthetic peptides, including GALA and nuclear localization signal peptides. We underscore the importance of understanding the mechanisms of cytoplasmic and nuclear entry of DNA and its dissociation from lipoplexes. We emphasize that the in vitro transfection activity of new lipoplex constructs should be tested in the presence of high serum concentrations to emulate in vivo conditions.

TAT-LHRH conjugated low molecular weight chitosan as a gene carrier specific for hepatocellular carcinoma cells

“…43 Therefore, it is crucial to ascertain that the gene-delivery systems should be able to effectively deliver genes into the cells in the presence of serum proteins. High transfection efficiency of chitosan in the presence of serum has been proved by several reports, which is a key advantage over other nonviral vectors such as polyethylenimine 29 and liposomes.…”

Recent advances in rational gene transfer vector design based on poly(ethylene imine) and its derivatives

“…Also, the limited loading capacity and difficulties in large-scale production of viral vectors have stimulated research into safe and effective non-viral vectors. Several strategies can be distinguished, among which the use of cationic lipids ('lipofection') or cationic polymers ('polyfection') has achieved some prominence [1,11,12].…”

Intracellular trafficking of nonviral vectors

“…Lipoplexes are comprised of DNA bound to cationic liposomes, which contain hydrophobic moieties thought to enable interaction with the plasma membrane. 2 Polyplexes contain hydrophilic polymers that are either linear, such as polylysine or spermine, or branched, such as polyethyleneimine (PEI) combined with DNA. [3][4][5] Combinations of cationic liposomes and polymers with DNA have been called lipopolyplexes.…”