Formation and intracellular trafficking of lipoplexes and polyplexes

Cationic lipid/DNA lipoplexes and cationic polymer/DNA polyplexes represent an attractive alternative to viral vectors for cell transfection in vitro and in vivo but still suffer from a relatively low efficiency. Optimization of their transfection efficiency may be attempted by using a trial and error approach consisting of synthesizing and testing a large number of derivatives. On the other hand, rational design of highly efficient cationic lipids and polymers requires a deeper understanding of the interactions between the vector and the DNA as well as the cellular pathways and mechanisms involved in DNA entry into the cell and ultimately the nucleus. in the present review, the pathways and mechanisms involved in lipoplex- and polyplex-mediated transfection are comparatively addressed and unresolved questions are highlighted.