Abstract
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.
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References
Subbarao, N. K., Parente, R. A., Szoka, F. C. Jr., Nadasdi, L., Pongracz, K. (1987) pH-dependent bilayer destabilization by an amphipathic peptide. Biochemistry 26, 2964–2972.
Li, W., Nicol, F., Szoka, F. C. Jr. (2004) GALA: a designed synthetic pH-responsive amphipathic peptide with applications in drug and gene delivery. Adv. Drug Deliv. Rev. 56, 967–985.
Futaki, S., Masui, Y., Nakase, I., Sugiura, Y., Nakamura, T., Kogure, K., Harashima, H. (2005) Unique features of a pH-sensitive fusogenic peptide that improves the transfection efficiency of cationic liposomes. J. Gene Med. 7, 1450–1458.
Simões, S., Slepushkin, V., Gaspar, R., de Lima, M. C., Düzgüneş, N. (1998) Gene delivery by negatively charged ternary complexes of DNA, cationic liposomes and transferrin or fusigenic peptides. Gene Ther. 5, 955–964.
Simões, S., Slepushkin, V., Pretzer, E., Dazin, P., Gaspar, R., Pedroso de Lima M. C., Düzgüneş, N. (1999) Transfection of human macrophages by lipoplexes via the combined use of transferrin and pH-sensitive peptides. J. Leukoc. Biol. 65, 270–279.
Sasaki, K., Kogure, K., Chaki, S., Nakamura, Y., Moriguchi, R., Hamada, H., Danev, R., Nagayama, K., Futaki, S., Harashima, H. (2008) An artificial virus-like nano carrier system: enhanced endosomal escape of nanoparticles via synergistic action of pH-sensitive fusogenic peptide derivatives. Anal. Bioanal. Chem. 391, 2717–2727.
Kobayashi, S., Nakase, I., Kawabata, N., Yu, H. H., Pujals, S., Imanishi, M., Giralt, E., Futaki, S. (2009) Cytosolic targeting of macromolecules using a pH-dependent fusogenic peptide in combination with cationic liposomes. Bioconjug. Chem. 20, 953–959.
Futaki, S., Niwa, M., Nakase, I., Tadokoro, A., Zhang, Y., Nagaoka, M., Wakako, N., Sugiura, Y. (2004) Arginine carrier peptide bearing Ni(II) chelator to promote cellular uptake of histidine-tagged proteins. Bioconjug. Chem. 15, 475–481.
Acknowledgment
This work was supported in part by Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.
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Nakase, I., Kogure, K., Harashima, H., Futaki, S. (2011). Application of a Fusiogenic Peptide GALA for Intracellular Delivery. In: Langel, Ü. (eds) Cell-Penetrating Peptides. Methods in Molecular Biology, vol 683. Humana Press. https://doi.org/10.1007/978-1-60761-919-2_37
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DOI: https://doi.org/10.1007/978-1-60761-919-2_37
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