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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/7817214d56e61-3500-41e1-a198-2dc4ff1cf5bf
Item type | 学術雑誌論文 / Journal Article(1) | |||||
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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× Foo, Wanling× Dirisala, Anjaneyulu× Chen, Qixian× Uchida, Satoshi× Osawa, Shigehito× Mochida, Yuki× Liu, Xueying× Kinoh, Hiroaki× Cabral, Horacio× Osada, Kensuke× Kataoka, Kazunori× Kensuke, Osada |
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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 |
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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 |