Delivery of therapeutic oligonucleotides targeting Dectin-1 using quantized complexes View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2022-02-22

AUTHORS

Kazuki Sumiya, Hiroto Izumi, Takuya Matsunaga, Motoko Tanaka, Kazuo Sakurai

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. More... »

PAGES

591-601

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41428-021-00595-8

DOI

http://dx.doi.org/10.1038/s41428-021-00595-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1145741467


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