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Identification and Evaluation of the Minimum Unit of a KALA Peptide Required for Gene Delivery and Immune Activation

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Title: Identification and Evaluation of the Minimum Unit of a KALA Peptide Required for Gene Delivery and Immune Activation
Authors: Miura, Naoya Browse this author
Tange, Kota Browse this author
Nakai, Yuta Browse this author
Yoshioka, Hiroki Browse this author
Harashima, Hideyoshi Browse this author →KAKEN DB
Akita, Hidetaka Browse this author
Keywords: non-viral gene delivery
peptides
circular dichroism
liposomes
vaccine delivery
vaccine adjuvants
gene vectors
Issue Date: Oct-2017
Publisher: Elsevier
Journal Title: Journal of Pharmaceutical Sciences
Volume: 106
Issue: 10
Start Page: 3113
End Page: 3119
Publisher DOI: 10.1016/j.xphs.2017.05.014
PMID: 28535977
Abstract: The KALA peptide (WEAKLAKALAKALAKHLAKALAKALKA) is an amphiphilic peptide that forms an a-helical structure at physiological pH. We previously reported that, when a plasmid DNA-encapsulating liposomal membrane is modified with the KALA peptide, transgene expression and immune activation are facilitated in bone marrow-derived dendritic cells (BMDCs). However, the minimum unit of the KALA peptide and the importance of its secondary structure for these activities are not completely known at this time. We herein report on the identification of the minimum unit of the KALA peptide (short-KALA) required for activity, as determined by the stepwise removal of "K-A-L-A" units. We evaluated the activities of 4 types of short-KALAs by modifying plasmid DNA-encapsulating multi-functional envelop-type nano devices. Among the peptides tested, a short-KALA3 (WEAKLAKALAKALA) was the shortest KALA peptide that could form an alpha-helical structure, as well as to elicit transgene expression and immune activation in BMDCs. Furthermore, the function of the short-KALA3 as an inducer of cellular uptake was retained, while uptake was completely lost in more shortened versions of KALA (short KALA4), in that transgene expression and immunological activation were both completely lost. These collective data show that the KALA peptide must form an alpha-helical structure to induce cellular uptake in BMDCs. (C) 2017 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.
Rights: © 2017. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/
http://creativecommons.org/licenses/by-nc-nd/4.0/
Type: article (author version)
URI: http://hdl.handle.net/2115/71765
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 原島 秀吉

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