Optimizing Charge Switching in Membrane Lytic Peptides for Endosomal Release of Biomacromolecules.

DOI DOI HANDLE Web Site Web Site ほか6件をすべて表示 一部だけ表示 被引用文献7件 参考文献30件 オープンアクセス
  • Sakamoto, Kentarou
    Institute for Chemical Research, Kyoto University
  • Akishiba, Misao
    Institute for Chemical Research, Kyoto University
  • Iwata, Takahiro
    Institute for Chemical Research, Kyoto University
  • Murata, Kazuya
    Laboratory Animal Resource Center, Transborder Medical Research Center, Faculty of Medicine, University of Tsukuba
  • Mizuno, Seiya
    Laboratory Animal Resource Center, Transborder Medical Research Center, Faculty of Medicine, University of Tsukuba
  • Kawano, Kenichi
    Institute for Chemical Research, Kyoto University
  • Imanishi, Miki
    Institute for Chemical Research, Kyoto University
  • Sugiyama, Fumihiro
    Laboratory Animal Resource Center, Transborder Medical Research Center, Faculty of Medicine, University of Tsukuba
  • Futaki, Shiroh
    Institute for Chemical Research, Kyoto University

抄録

Endocytic pathways are practical routes for the intracellular delivery of biomacromolecules. Along with this, effective strategies for endosomal cargo release into the cytosol are desired to achieve successful delivery. Focusing on compositional differences between the cell and endosomal membranes and the pH decrease within endosomes, we designed the lipid-sensitive and pH-responsive endosome-lytic peptide HAad. This peptide contains aminoadipic acid (Aad) residues, which serve as a safety catch for preferential permeabilization of endosomal membranes over cell membranes, and His-to-Ala substitutions enhance the endosomolytic activity. The ability of HAad to destabilize endosomal membranes was supported by model studies using large unilamellar vesicles (LUVs) and by increased intracellular delivery of biomacromolecules (including antibodies) into live cells. Cerebral ventricle injection of Cre recombinase with HAad led to Cre/loxP recombination in a mouse model, thus demonstrating potential applicability of HAad in vivo.

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