Nakase Ikuhiko, Kogure Kentaro, Harashima Hideyoshi, Futaki Shiroh
Institute for Chemical Research, Kyoto University, Uji, Kyoto, Japan.
Methods Mol Biol. 2011;683:525-33. doi: 10.1007/978-1-60761-919-2_37.
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.
为提高治疗性药物和基因的胞质递送效率，pH敏感且具有膜融合性的肽已被用作添加剂，以促进它们从内体中逃逸。GALA就是这样一种由Glu-Ala-Leu-Ala重复序列组成的肽，其设计目的是模拟病毒融合蛋白序列的功能，介导病毒基因从酸性内体逃逸到细胞质中。最近，这种肽不仅被用于提高使用阳离子脂质体的质粒DNA转染效率，还被用作多功能包膜型纳米装置（MEND）的功能分子。在阳离子脂质复合物存在的情况下，通过GALA-货物缀合物的有效内体逃逸实现蛋白质的胞质递送，也例证了使用这种肽的优势。本章提供了使用GALA肽有效进行货物分子胞质递送的方案。
