Self-Degradable Lipid-Like Materials Based on “Hydrolysis accelerated by the intra-Particle Enrichment of Reactant (HyPER)” for Messenger RNA Delivery

Hiroki Tanaka, Tatsunari Takahashi, Manami Konishi, Nae Takata, Masaki Gomi, Daiki Shirane, Ryo Miyama, Shinya Hagiwara, Yuki Yamasaki, Yu Sakurai, Keisuke Ueda, Kenjirou Higashi, Kunikazu Moribe, Eiji Shinsho, Ruka Nishida, Kaori Fukuzawa, Etsuo Yonemochi, Koji Okuwaki, Yuji Mochizuki, Yuta NakaiKota Tange, Hiroki Yoshioka, Shinya Tamagawa, Hidetaka Akita

研究成果: Article査読

47 被引用数 (Scopus)

抄録

RNA-based therapeutics is a promising approach for curing intractable diseases by manipulating various cellular functions. For eliciting RNA (i.e., mRNA and siRNA) functions successfully, the RNA in the extracellular space must be protected and it must be delivered to the cytoplasm. In this study, the development of a self-degradable lipid-like material that functions to accelerate the collapse of lipid nanoparticles (LNPs) and the release of RNA into cytoplasm is reported. The self-degradability is based on a unique reaction “Hydrolysis accelerated by intra-Particle Enrichment of Reactant (HyPER).” In this reaction, a disulfide bond and a phenyl ester are essential structural components: concentrated hydrophobic thiols that are produced by the cleavage of the disulfide bonds in the LNPs drive an intraparticle nucleophilic attack to the phenyl ester linker, which results in further degradation. An oleic acid-scaffold lipid-like material that mounts all of these units (ssPalmO-Phe) shows superior transfection efficiency to nondegradable or conventional materials. The insertion of the aromatic ring is unexpectedly revealed to contribute to the enhancement of endosomal escape. Since the intracellular trafficking is a sequential process that includes cellular uptake, endosomal escape, the release of mRNA, and translation, the improvement in each process synergistically enhances the gene expression.

本文言語English
論文番号1910575
ジャーナルAdvanced Functional Materials
30
34
DOI
出版ステータスPublished - 2020 8月 1
外部発表はい

ASJC Scopus subject areas

  • 化学 (全般)
  • 材料科学(全般)
  • 凝縮系物理学

フィンガープリント

「Self-Degradable Lipid-Like Materials Based on “Hydrolysis accelerated by the intra-Particle Enrichment of Reactant (HyPER)” for Messenger RNA Delivery」の研究トピックを掘り下げます。これらがまとまってユニークなフィンガープリントを構成します。

引用スタイル