論文

査読有り 国際誌
2020年3月18日

Stimulating Macropinocytosis for Intracellular Nucleic Acid and Protein Delivery: A Combined Strategy with Membrane-Lytic Peptides To Facilitate Endosomal Escape.

Bioconjugate chemistry
  • Jan Vincent V Arafiles
  • ,
  • Hisaaki Hirose
  • ,
  • Misao Akishiba
  • ,
  • Shogo Tsuji
  • ,
  • Miki Imanishi
  • ,
  • Shiroh Futaki

31
3
開始ページ
547
終了ページ
553
記述言語
英語
掲載種別
DOI
10.1021/acs.bioconjchem.0c00064

Delivery of biomacromolecules via endocytic pathways requires the efficient accumulation of cargo molecules into endosomes, followed by their release to the cytosol. We propose a unique intracellular delivery strategy for bioactive molecules using a new potent macropinocytosis-inducing peptide derived from stromal-derived factor 1α (SN21). This peptide allowed extracellular materials to enter cells through the activation of macropinocytosis. To provide the ability to release internalized cargoes from endosomes, we conjugated SN21 with membrane-lytic peptides. The combination of a macropinocytosis-inducing peptide and a membrane-lytic peptide successfully delivered functional siRNA and proteins, which include antibodies, Cre recombinase, and an artificial transcription regulator protein having a transcription activator-like effector (TALE) motif. This study shows the feasibility of combining the physiological stimulation of macropinocytosis with the physicochemical disruption of endosomes as a strategy for intracellular delivery.

リンク情報
DOI
https://doi.org/10.1021/acs.bioconjchem.0c00064
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32017537

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