Strategies to enhance the eff ectiveness of the lipoplexes used to deliver plasmids and other DNA/RNA oligonucleotides involve manipulation of the lipoplex lipid content and the use of targeting peptides. Th e choice of lipid infl uences expression effi ciency by enhancing release of the genetic material within the target cell [73, 74] . Targeting peptides increases transfection effi ciency by directing the lipid to a particular cell membrane or cell type [31] . Physical methods of plasmid delivery such as electroporation [60] and ultrasound can enhance gene transfer by bringing the plasmid DNA into closer proximity with the cell membrane and/or causing temporary disruption of the cell membrane. Other physical methods can also be used to increase in vivo gene transfer, including pressurized vascular delivery, laser, magnetic fi elds and gene gun delivery. Th ese systems enable plasmid-based gene delivery to reach effi ciencies close to that achieved with viral vectors.