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Title: Stimulating Macropinocytosis for Intracellular Nucleic Acid and Protein Delivery: A Combined Strategy with Membrane-Lytic Peptides to Facilitate Endosomal Escape
Authors: Arafiles, Jan Vincent V.
Hirose, Hisaaki
Akishiba, Misao
Tsuji, Shogo
Imanishi, Miki  kyouindb  KAKEN_id  orcid https://orcid.org/0000-0002-4172-0966 (unconfirmed)
Futaki, Shiroh
Author's alias: 今西, 未来
二木, 史朗
Issue Date: 18-Mar-2020
Publisher: American Chemical Society
Journal title: Bioconjugate Chemistry
Volume: 31
Issue: 3
Start page: 547
End page: 553
Abstract: 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.
Rights: This document is the Accepted Manuscript version of a Published Work that appeared in final form in Bioconjugate Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://doi.org/10.1021/acs.bioconjchem.0c00064.
This is not the published version. Please cite only the published version.
この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
URI: http://hdl.handle.net/2433/261214
DOI(Published Version): 10.1021/acs.bioconjchem.0c00064
PubMed ID: 32017537
Appears in Collections:Journal Articles

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