Hoechst-Modification on Oligodeoxynucleotides for Efficient Transport to the Cell Nucleus and Gene Regulation.

Various artificial oligodeoxynucleotides (ODNs) that contribute to gene regulation have been developed and their diversity and multifunctionality have been demonstrated. However, few artificial ODNs are actively transported to the cell nucleus, despite the fact that gene regulation also takes place in both the cell nucleus and the cytoplasm. In this study, to prepare ODNs with the ability to accumulate in the cell nucleus, we introduced Hoechst molecules into ODNs that act as carriers of functional molecules to the cell nucleus (Hoe-ODNs). We synthesized Hoe-ODNs and confirmed that they bound strongly to DNA duplexes. When single-stranded Hoe-ODNs or double-stranded ODNs consisting of Hoe-ODNs and its complementary strand were administered into living cells, both ODNs were efficiently accumulated in the cell nucleus. In addition, antisense ODNs, which were tethered with Hoechst unit, were delivered into the cell nucleus and efficiently suppressed the expression of their target RNA. Thus, we constructed a delivery system that enables the transport of ODNs into cell nucleus. © 2023 Wiley-VCH GmbH.

Citation

Hiroki Makanai, Tatsuya Nishihara, Makiya Nishikawa, Kazuhito Tanabe. Hoechst-Modification on Oligodeoxynucleotides for Efficient Transport to the Cell Nucleus and Gene Regulation. Chembiochem : a European journal of chemical biology. 2024 Feb 01;25(3):e202300645

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PMID: 37984902

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