Application of a fusiogenic peptide GALA for intracellular delivery

To enhance the cytosolic delivery of therapeutic drugs and genes, pH-sensitive and membrane fusiogenic peptides have been employed as additives for facilitating their endosomal escape. GALA is such a peptide composed of repeating sequences of Glu-Ala-Leu-Ala, which are designed to mimic the function of viral fusion protein sequences that mediate escape of virus genes from acidic endosomes to the cytosol. Recently, the peptide has been applied not only for improving the transfection efficiency of plasmid DNAs using cationic liposomes, but also as functional molecules of multifunctional envelope-type nanodevice (MEND). The advantage of employing this peptide was also exemplified by the cytosolic delivery of proteins via efficient endosomal escape of the GALA-cargo conjugates in the presence of cationic lipid complexes. This chapter provides protocols for the efficient cytosolic delivery of cargo molecules using the GALA peptide.