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タイトル: Treatment of neurological disorders by introducing mRNA in vivo using polyplex nanomicelles
著者: Baba, Miyuki
Itaka, Keiji
Kondo, Kenji
Yamasoba, Tatsuya
Kataoka, Kazunori
キーワード: Messenger RNA (mRNA) administration
Neurological disorders
Olfactory dysfunction
Brain-derived neurotrophic factor (BDNF)
mRNA-based therapy
発行日: 2015年
出版者: Elsevier
掲載誌情報: Journal of Controlled Release 201: 41-48 (2015). doi:10.1016/j.jconrel.2015.01.017
関連URI: http://www.u-tokyo.ac.jp/ja/utokyo-research/research-news/a-new-system-of-gene-therapy-using-messenger-rna-mrna.html
http://www.u-tokyo.ac.jp/en/utokyo-research/research-news/a-new-system-of-gene-therapy-using-messenger-rna-mrna.html
http://www.sciencedirect.com/science/article/pii/S0168365915000577
抄録: 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: 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
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
URI: http://hdl.handle.net/2261/56528
ISSN: 0168-3659
出現カテゴリ:014 自然科学
1125010 学術雑誌論文

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