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Treatment of neurological disorders by introducing mRNA in vivo using polyplex nanomicelles
http://hdl.handle.net/2261/56528
http://hdl.handle.net/2261/565281c7ebb38-0c3d-4ccc-abf7-576c7913cc21
名前 / ファイル | ライセンス | アクション |
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JCR-D-14-01314R1_author_manuscript.pdf (1.4 MB)
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Item type | 学術雑誌論文 / Journal Article(1) | |||||
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公開日 | 2015-03-03 | |||||
タイトル | ||||||
タイトル | Treatment of neurological disorders by introducing mRNA in vivo using polyplex nanomicelles | |||||
言語 | ||||||
言語 | eng | |||||
キーワード | ||||||
主題 | Messenger RNA (mRNA) administration | |||||
主題Scheme | Other | |||||
キーワード | ||||||
主題 | Neurological disorders | |||||
主題Scheme | Other | |||||
キーワード | ||||||
主題 | Olfactory dysfunction | |||||
主題Scheme | Other | |||||
キーワード | ||||||
主題 | Brain-derived neurotrophic factor (BDNF) | |||||
主題Scheme | Other | |||||
キーワード | ||||||
主題 | mRNA-based therapy | |||||
主題Scheme | Other | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_6501 | |||||
タイプ | journal article | |||||
著者 |
Baba, Miyuki
× Baba, Miyuki× Itaka, Keiji× Kondo, Kenji× Yamasoba, Tatsuya× Kataoka, Kazunori |
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著者所属 | ||||||
著者所属 | Laboratory of Clinical Biotechnology, Center for Disease Biology and Integrative Medicine, Graduate School of Medicine, The University of Tokyo | |||||
著者所属 | ||||||
著者所属 | Department of Otolaryngology, Head and Neck Surgery, Faculty of Medicine, The University of Tokyo | |||||
著者所属 | ||||||
著者所属 | Department of Materials Engineering, Graduate School of Engineering, The University of Tokyo | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Sensory nerve disorders are difficult to cure completely considering poor nerve regeneration capacity and difficulties in accurately targeting neural tissues. Administering mRNA is a promising approach for treating neurological disorders because mRNA can provide proteins and peptides in their native forms for mature non-dividing neural cells, without the need of entering their nuclei. However, direct mRNA administration into neural tissues in vivo has been challenging due to too unstable manner of mRNA and its strong immunogenicity. Thus, using a suitable carrier is essential for effective mRNA administration. For this purpose, we established a novel carrier based on the self-assembly of polyethylene glycol (PEG)–polyamino acid block copolymer, i.e. polyplex nanomicelles. To investigate the feasibility and efficacy of mRNA administration for the treatment of sensory nerve disorders, we used a mouse model of experimentally induced olfactory dysfunction. Intranasal administration of mRNA-loaded nanomicelles provided an efficient and sustained protein expression for nearly two days in nasal tissues, particularly in the lamina propria which contains olfactory nerve fibers, with effectively regulating the immunogenicity of mRNA. Consequently, once-daily intranasal administration of brain-derived neurotrophic factor (BDNF)-expressing mRNA using polyplex nanomicelles remarkably enhanced the neurological recovery of olfactory function along with repairing the olfactory epithelium to a nearly normal architecture. To the best of our knowledge, this is the first study to show the therapeutic potential of introducing exogenous mRNA for the treatment of neurological disorders. These results indicate the feasibility and safety of using mRNA, and provide a novel strategy of mRNA-based therapy. | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | UTokyo Research掲載「メッセンジャーRNAを用いた新しい遺伝子治療」 URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/a-new-system-of-gene-therapy-using-messenger-rna-mrna.html | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | UTokyo Research "A new system of gene therapy using messenger RNA (mRNA)" URI: http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/a-new-system-of-gene-therapy-using-messenger-rna-mrna.html | |||||
書誌情報 |
Journal of controlled release 巻 201, p. 41-48, 発行日 2015 |
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ISSN | ||||||
収録物識別子タイプ | ISSN | |||||
収録物識別子 | 0168-3659 | |||||
書誌レコードID | ||||||
収録物識別子タイプ | NCID | |||||
収録物識別子 | AA10458678 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | info:doi/10.1016/j.jconrel.2015.01.017 | |||||
権利 | ||||||
権利情報 | Copyright (C) 2015 Elsevier B.V. All rights reserved. | |||||
著者版フラグ | ||||||
値 | author | |||||
出版者 | ||||||
出版者 | Elsevier | |||||
関係URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/a-new-system-of-gene-therapy-using-messenger-rna-mrna.html | |||||
関係URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/a-new-system-of-gene-therapy-using-messenger-rna-mrna.html | |||||
関係URI | ||||||
識別子タイプ | URI | |||||
関連識別子 | http://www.sciencedirect.com/science/article/pii/S0168365915000577 |