Malonic acid based cationic lipids - The way to highly efficient DNA-carriers

Cationic lipids play an important role as non-viral nucleic acid carriers in gene therapy since 3 decades. This review will introduce malonic acid derived cationic lipids as nucleic acid carriers which appeared in the literature dealing with lipofection 10years ago. The family of amino-functionalized branched fatty acid amides will be presented as well as different generations of malonic acid diamides. Both groups of cationic lipids yield lipid mixtures with highly efficient nucleic acid transfer activities in in-vitro cell culture models. The DNA transfer screening of lipid libraries with directed structural variations in the lipophilic as well as in the hydrophilic part of the amphiphiles yields structure/activity relationships. Furthermore, the detailed characterizations of selected lipid composites at the air/water interface and in bulk systems are summarized with regard to transfection determining physical-chemical properties. The findings are also discussed in comparison to results obtained with other families of cationic lipids.