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mRNA loading into ATP-responsive polyplex micelles with optimal density of phenylboronate ester crosslinking to balance robustness in the biological milieu and intracellular translational efficiency.
https://repo.qst.go.jp/records/81675
https://repo.qst.go.jp/records/81675217ff59c-6076-43c5-bac6-3275acb7c9c0
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2021-01-15 | |||||
| タイトル | ||||||
| タイトル | mRNA loading into ATP-responsive polyplex micelles with optimal density of phenylboronate ester crosslinking to balance robustness in the biological milieu and intracellular translational efficiency. | |||||
| 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 |
Yoshinaga, Naoto
× Yoshinaga, Naoto× Uchida, Satoshi× Dirisala, Anjaneyulu× Naito, Mitsuru× Osada, Kensuke× Cabral, Horacio× Kataoka, Kazunori× Kensuke, Osada |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Carriers for messenger RNA (mRNA) delivery require propensities to protect the mRNA from enzymatic degradation and to selectively release mRNA in the cytosol for smooth mRNA translation. To meet these requirements, we designed mRNA-loaded polyplex micelles (PMs) with ATP-responsive crosslinking in the inner core by complexing mRNA with poly(ethylene glycol)-polycation block copolymers derivatized with phenylboronic acid and polyol groups, which form crosslinking structures via spontaneous phenylboronate ester formation. PMs thus prepared are tolerable against enzymatic attack and, in turn, disintegrate in the cytosol to release mRNA when triggered by the cleavage of phenylboronate ester linkages in response to elevated ATP concentration. Two structural factors of the PM, including (i) the introduction ratios of phenylboronate ester crosslinkers and (ii) the structure and protonation degree of amino groups in the polycation segment, are critical for maximizing protein expression in cultured cells due to the optimized balance between the robustness in the biological milieu and the ATP-responsive mRNA release in the cytosol. The optimal PM formulation was further stabilized by installing cholesterol moieties into both the mRNA and ω-end of the block copolymer to elicit longevity in blood circulation after intravenous injection. | |||||
| 書誌情報 |
Journal of Controlled Release 巻 330, p. 317-328, 発行日 2021-01 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0168-3659 | |||||
| PubMed番号 | ||||||
| 識別子タイプ | PMID | |||||
| 関連識別子 | 33359053 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1016/j.jconrel.2020.12.033 | |||||
| 関連サイト | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.sciencedirect.com/science/article/abs/pii/S0168365920307574 | |||||
