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  1. 原著論文

Single-Stranded DNA-Packaged Polyplex Micelle as Adeno-Associated-Virus-Inspired Compact Vector to Systemically Target Stroma-Rich Pancreatic Cancer

https://repo.qst.go.jp/records/78172
https://repo.qst.go.jp/records/78172
14d56e61-3500-41e1-a198-2dc4ff1cf5bf
Item type 学術雑誌論文 / Journal Article(1)
公開日 2019-12-20
タイトル
タイトル Single-Stranded DNA-Packaged Polyplex Micelle as Adeno-Associated-Virus-Inspired Compact Vector to Systemically Target Stroma-Rich Pancreatic Cancer
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 A Tockary, Theofilus

× A Tockary, Theofilus

WEKO 998626

A Tockary, Theofilus

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Foo, Wanling

× Foo, Wanling

WEKO 998627

Foo, Wanling

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Dirisala, Anjaneyulu

× Dirisala, Anjaneyulu

WEKO 998628

Dirisala, Anjaneyulu

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Chen, Qixian

× Chen, Qixian

WEKO 998629

Chen, Qixian

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Uchida, Satoshi

× Uchida, Satoshi

WEKO 998630

Uchida, Satoshi

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Osawa, Shigehito

× Osawa, Shigehito

WEKO 998631

Osawa, Shigehito

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Mochida, Yuki

× Mochida, Yuki

WEKO 998632

Mochida, Yuki

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Liu, Xueying

× Liu, Xueying

WEKO 998633

Liu, Xueying

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Kinoh, Hiroaki

× Kinoh, Hiroaki

WEKO 998634

Kinoh, Hiroaki

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Cabral, Horacio

× Cabral, Horacio

WEKO 998635

Cabral, Horacio

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Osada, Kensuke

× Osada, Kensuke

WEKO 998636

Osada, Kensuke

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Kataoka, Kazunori

× Kataoka, Kazunori

WEKO 998637

Kataoka, Kazunori

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Kensuke, Osada

× Kensuke, Osada

WEKO 998638

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抄録
内容記述タイプ Abstract
内容記述 Despite the rigidity of double-stranded DNA (dsDNA), its packaging is used to construct nonviral gene carriers due to its availability and the importance of its double-helix to elicit transcription. However, there is an increasing demand for more compact-sized carriers to facilitate tissue penetration, which may be easily fulfilled by using the more flexible single-stranded DNA (ssDNA) as an alternative template. Inspired by the adeno-associated virus (AAV) as a prime example of a transcriptionally active ssDNA system, we considered a methodology that can capture unpaired ssDNA within the polyplex micelle system (PM), an assembly of DNA and poly(ethylene glycol)--poly(l-lysine) (PEG-PLys). A micellar assembly retaining unpaired ssDNA was prepared by unpairing linearized pDNA with heat and performing polyion complexation on site with PEG-PLys. The PM thus formed had a compact and spherical shape, which was distinguishable from the rod-shaped PM formed from dsDNA, and still retained its ability to activate gene expression. Furthermore, we demonstrated that its capacity to encapsulate DNA was much higher than AAV, thereby potentially allowing the delivery of a larger variety of protein-encoding DNA. These features permit the ssDNA-loaded PM to easily penetrate the size-restricting stromal barrier after systemic application. Further, they can elicit gene expression in tumor cell nests of an intractable pancreatic cancer mouse model to achieve antitumor effects through suicide gene therapy. Thus, single-stranded DNA-packaged PM is appealing as a potential gene vector to tackle intractable diseases, particularly those with target delivery issues due to size-restriction barriers.
書誌情報 ACS Nano

巻 13, 号 11, p. 12732-12742, 発行日 2019-11
出版者
出版者 ACS
ISSN
収録物識別子タイプ ISSN
収録物識別子 1936-0851
PubMed番号
識別子タイプ PMID
関連識別子 31647640
DOI
識別子タイプ DOI
関連識別子 10.1021/acsnano.9b04676
関連サイト
識別子タイプ URI
関連識別子 https://pubs.acs.org/doi/10.1021/acsnano.9b04676
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