Cationic lipids for gene delivery: many players, one goal.

Lipid-based carriers represent the most widely used alternative to viral vectors for gene expression and gene silencing purposes. This class of non-viral vectors is particularly attractive for their ease of synthesis and chemical modifications to endow them with desirable properties. Despite combinatorial approaches have led to the generation of a large number of cationic lipids displaying different supramolecular structures and improved behavior, additional effort is needed towards the development of more and more effective cationic lipids for transfection purposes. With this review, we seek to highlight the great progress made in the design of each and every constituent domain of cationic lipids, that is, the chemical structure of the headgroup, linker and hydrophobic moieties, and on the specific effect on the assembly with nucleic acids. Since the complexity of such systems is known to affect their performances, the role of formulation, stability and phase behavior on the transfection efficiency of such assemblies will be thoroughly discussed. Our objective is to provide a conceptual framework for the development of ever more performing lipid gene delivery vectors.