Another concept makes use of photosensitive substances, which induce the release of macromolecules from vesicles by light exposure. This so-called photochemical internalization (PCI) has, in the past, been used for intracellular delivery of a large variety of macromolecules (reviewed in [185] ) and, more recently, for the endosomal release of nucleic acids after delivery mediated by liposomes [186, 187] , polyplexes [188] or CPPs [138, 189] . Shiraishi et al. [138] investigated the biological activity of PNAs conjugated either to Tat, R7 or KLA-peptide in combination with a PCI treatment. Depending on the peptide, nuclear as well as cytosolic antisense effects could be enhanced by up to two orders of magnitude. Similar results were presented by Folini et al. [189] for a PNA targeting human telomerase reverse transcriptase conjugated to Tat. In both studies, lower nucleic acid doses were sufficient, thereby reducing the probability of off-target effects. In light of encouraging data from ongoing anticancer clinical trials employing photodynamic therapy [190, 191] , an in vivo application of PCI seems feasible and will be discussed in more detail by Oliveira et al. [192] in this issue. Furthermore, target specificity could be increased by local illumination of cells or tissue. Viral fusion proteins drive the fusion process between the viral membrane and the endosomal host cell membrane in a pH-dependent manner, which is required to translocate the viral genome into the cytoplasm after receptor-mediated endocytosis. Fusogenic peptides, usually hydrophobic, rich in glycine residues and found at the amino terminus of these proteins, were shown to have membrane perturbing and lipid mixing activities [193] . Many well studied representatives of this group are derived from the fusion sequence of influenza virus HA or HIV-1 gp41 [194] and have been used to improve the transfection efficiency of non-viral delivery systems [195] .