Synthesis, structure, and biological activity of dumbbell-shaped nanocircular RNAs for RNA interference

Naoko Abe, Hiroshi Abe, Chisato Nagai, Mitsuru Harada, Hiroto Hatakeyama, Hideyoshi Harashima, Takahito Ohshiro, Mizuki Nishihara, Kazuhiro Furukawa, Mizuo Maeda, Satoshi Tsuneda, Yoshihiro Ito

    Research output: Contribution to journalArticle

    26 Citations (Scopus)

    Abstract

    RNA interference (RNAi) is one of the most promising new approaches for disease therapy. The design of a dumbbell-shaped nanocircular RNA allows it to act as a short interfering RNA (siRNA) precursor. To optimize the design, we studied the relationship between the nanostructure and RNAi activity by synthesizing various RNA dumbbells. An RNA dumbbell with a 23-bp stem and 9-nt loops was the most potent. Sequence analysis by mass spectrometry showed that Dicer could edit RNA dumbbells to siRNA species. The reaction offered the slow release of siRNA species, which conferred prolonged RNAi activity. Introduction of DNA into the loop position significantly stabilized the dumbbell in biological fluid without any loss of RNAi activity. In-depth pharmacological evaluation was performed by introducing dumbbells into HeLa cells that stably express the target luciferase gene. The dumbbells provided a rapid silencing effect and retained this effect for a longer time even at a lower concentration than that at which standard siRNA completely lost RNAi activity. We conclude that an RNA dumbbell with DNA loops is the most promising design for in vivo applications for RNA medicine.

    Original languageEnglish
    Pages (from-to)2082-2092
    Number of pages11
    JournalBioconjugate Chemistry
    Volume22
    Issue number10
    DOIs
    Publication statusPublished - 2011 Oct 19

    Fingerprint

    RNA Interference
    Bioactivity
    RNA
    Small Interfering RNA
    Nanostructures
    DNA
    RNA Precursors
    Luciferases
    HeLa Cells
    Sequence Analysis
    Mass Spectrometry
    Medicine
    Pharmacology
    Mass spectrometry
    Genes
    Fluids

    ASJC Scopus subject areas

    • Biotechnology
    • Bioengineering
    • Organic Chemistry
    • Pharmaceutical Science
    • Biomedical Engineering
    • Pharmacology

    Cite this

    Abe, N., Abe, H., Nagai, C., Harada, M., Hatakeyama, H., Harashima, H., ... Ito, Y. (2011). Synthesis, structure, and biological activity of dumbbell-shaped nanocircular RNAs for RNA interference. Bioconjugate Chemistry, 22(10), 2082-2092. https://doi.org/10.1021/bc2003154

    Synthesis, structure, and biological activity of dumbbell-shaped nanocircular RNAs for RNA interference. / Abe, Naoko; Abe, Hiroshi; Nagai, Chisato; Harada, Mitsuru; Hatakeyama, Hiroto; Harashima, Hideyoshi; Ohshiro, Takahito; Nishihara, Mizuki; Furukawa, Kazuhiro; Maeda, Mizuo; Tsuneda, Satoshi; Ito, Yoshihiro.

    In: Bioconjugate Chemistry, Vol. 22, No. 10, 19.10.2011, p. 2082-2092.

    Research output: Contribution to journalArticle

    Abe, N, Abe, H, Nagai, C, Harada, M, Hatakeyama, H, Harashima, H, Ohshiro, T, Nishihara, M, Furukawa, K, Maeda, M, Tsuneda, S & Ito, Y 2011, 'Synthesis, structure, and biological activity of dumbbell-shaped nanocircular RNAs for RNA interference', Bioconjugate Chemistry, vol. 22, no. 10, pp. 2082-2092. https://doi.org/10.1021/bc2003154
    Abe, Naoko ; Abe, Hiroshi ; Nagai, Chisato ; Harada, Mitsuru ; Hatakeyama, Hiroto ; Harashima, Hideyoshi ; Ohshiro, Takahito ; Nishihara, Mizuki ; Furukawa, Kazuhiro ; Maeda, Mizuo ; Tsuneda, Satoshi ; Ito, Yoshihiro. / Synthesis, structure, and biological activity of dumbbell-shaped nanocircular RNAs for RNA interference. In: Bioconjugate Chemistry. 2011 ; Vol. 22, No. 10. pp. 2082-2092.
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