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Delivery of therapeutic oligonucleotides targeting Dectin-1 using quantized complexes

Polymer Journal volume 54, pages 591–601 (2022)Cite this article

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Abstract

Finding an appropriate carrier for antisense oligonucleotides (AS-ODNs) and improving the efficiency of their delivery to cells and organs has been critical for the translation of antisense therapy into practice for more than 30 years. We have used a β-glucan, schizophyllan (SPG), as a delivery tool to solve this issue. SPG forms a complex with AS-ODNs that can be taken up by cells expressing the β-glucan receptor Dectin-1. We used SPG/AS-DNA complexes containing four to ten ODNs with a relatively large distribution of molecular weights. We recently discovered a complex in which the number of AS-ODNs can be accurately controlled and denoted it as a quantized complex. Building on our previous work, this paper presents the biological properties of this new quantized complex, including its efficacy for cells expressing Dectin-1 and the mechanism behind its cellular uptake of gene-silenced AS-ODNs and immunostimulatory CpG-ODNs. We found that this new complex is also recognized by Dectin-1, and interestingly, is more effective than the conventional complexes, owing to its easier escape from the endocytotic pathway.

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Acknowledgements

We gratefully thank Mr. Shogo Sasaki for technical assistance. This work was financially supported by JST CREST and by JSPS KAKENHI: Grant-in-Aid for Scientific Research A (20H00668) and Grant-in-Aid for Challenging Exploratory Research (20K20449).

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Authors and Affiliations

  1. Department of Chemistry and Biochemistry, University of Kitakyushu, Kitakyushu, Fukuoka, Japan

    Kazuki Sumiya, Takuya Matsunaga, Motoko Tanaka & Kazuo Sakurai

  2. Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu, Fukuoka, Japan

    Hiroto Izumi

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  1. Kazuki Sumiya
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Correspondence to Hiroto Izumi or Kazuo Sakurai.

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Sumiya, K., Izumi, H., Matsunaga, T. et al. Delivery of therapeutic oligonucleotides targeting Dectin-1 using quantized complexes. Polym J 54, 591–601 (2022). https://doi.org/10.1038/s41428-021-00595-8

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