Lipids and nucleic acids (NAs) can hierarchically self-organize into a variety of nanostructures of increasingly complex geometries such as the 1D lamellar, 2D hexagonal, and 3D bicontinuous cubic phases. The diversity and complexity of those lipid-NA assemblies are interesting from a fundamental perspective as well as being relevant to the performance in gene delivery and gene silencing applications. The finding that not only the chemical make of the lipid-NA constructs, but their actual supramolecular organization, affects their gene transfection and silencing efficiencies has inspired physicists, chemists, and engineers to this field of research. At the moment it remains an open question how exactly the different lipid-NA structures interact with cells and organelles in order to output an optimal response. This article reviews our current understanding of the structures of different lipid-NA complexes and the corresponding cellular interaction mechanisms. The recent advances in designing optimal lipid-based NA carriers will be introduced with an emphasis on the structure-function relations.
Keywords: gene delivery; lipid-DNA; lipid-siRNA; self-assembly.