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  1. 原著論文

Precise tuning of disulphide crosslinking in mRNA polyplex micelles for optimising extracellular and intracellular nuclease tolerability.

https://repo.qst.go.jp/records/75752
https://repo.qst.go.jp/records/75752
face248c-84f1-495e-af05-8269ff10ea36
Item type 学術雑誌論文 / Journal Article(1)
公開日 2019-05-07
タイトル
タイトル Precise tuning of disulphide crosslinking in mRNA polyplex micelles for optimising extracellular and intracellular nuclease tolerability.
言語
言語 eng
資源タイプ
資源タイプ識別子 http://purl.org/coar/resource_type/c_6501
資源タイプ journal article
アクセス権
アクセス権 metadata only access
アクセス権URI http://purl.org/coar/access_right/c_14cb
著者 Dirisala, Anjaneyulu

× Dirisala, Anjaneyulu

WEKO 1001673

Dirisala, Anjaneyulu

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Uchida, Satoshi

× Uchida, Satoshi

WEKO 1001674

Uchida, Satoshi

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A Tockary, Theofilus

× A Tockary, Theofilus

WEKO 1001675

A Tockary, Theofilus

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Yoshinaga, Naoto

× Yoshinaga, Naoto

WEKO 1001676

Yoshinaga, Naoto

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Li, Junjie

× Li, Junjie

WEKO 1001677

Li, Junjie

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Osawa, Shigehito

× Osawa, Shigehito

WEKO 1001678

Osawa, Shigehito

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Gorantla, Lahari

× Gorantla, Lahari

WEKO 1001679

Gorantla, Lahari

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Fukushima, Shigeto

× Fukushima, Shigeto

WEKO 1001680

Fukushima, Shigeto

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Osada, Kensuke

× Osada, Kensuke

WEKO 1001681

Osada, Kensuke

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Kataoka, Kazunori

× Kataoka, Kazunori

WEKO 1001682

Kataoka, Kazunori

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Kensuke, Osada

× Kensuke, Osada

WEKO 1001683

en Kensuke, Osada

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抄録
内容記述タイプ Abstract
内容記述 The major issues in messenger (m)RNA delivery are rapid mRNA degradation in the extracellular and intracellular spaces, which decreases the efficiency and duration for protein expression from mRNA. Stabilization of mRNA carriers using environment-responsive crosslinkings has promises to overcome these issues. Herein, we fine-tuned the structure of disulphide crosslinkings, which are selectively cleaved in the intracellular reductive environment, using the mRNA-loaded polyplex micelles (PMs) prepared from poly(ethylene glycol)-poly(L-lysine) (PEG-PLys) block copolymers, particularly by focussing on cationic charge density after the crosslinking. Primary amino groups in PLys segment were partially thiolated in two ways: One is to introduce 3-mercaptopropionyl (MP) groups via amide linkage, resulting in the decreased cationic charge density [PEG-PLys(MP)], and the other is the conversion of amino groups to 1-amidine-3-mercaptopropyl (AMP) groups with preserving cationic charge density [PEG-PLys(AMP)]. Compared to non-crosslinked and PEG-PLys(MP) PMs, PEG-PLys(AMP) PM attained tighter mRNA packaging in the PM core, thereby improving mRNA nuclease tolerability in serum and intracellular spaces, and providing enhanced protein expression in cultured cells at the optimal crosslinking density. These findings highlight the importance of cationic charge preservation in installing crosslinking moieties, providing a rationale for mRNA carrier design in the molecular level.
書誌情報 Journal of drug targeting

巻 27, 号 5-6, p. 670-680, 発行日 2019-04
出版者
出版者 Informa Healthcare
ISSN
収録物識別子タイプ ISSN
収録物識別子 1061-186X
PubMed番号
識別子タイプ PMID
関連識別子 30499743
DOI
識別子タイプ DOI
関連識別子 10.1080/1061186X.2018.1550646
関連サイト
識別子タイプ URI
関連識別子 https://www.tandfonline.com/doi/full/10.1080/1061186X.2018.1550646
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