Department of Chemistry and Biological Science, College of Science and Engineering, Aoyama Gakuin University, 5-10-1 Fuchinobe, Chuo-ku, Sagamihara, 252-5258, Japan.
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba, 278-8510, Japan.
Chembiochem. 2024 Feb 1;25(3):e202300645. doi: 10.1002/cbic.202300645. Epub 2023 Dec 4.
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.
已经开发出了各种有助于基因调控的人工寡脱氧核苷酸（ODN），并证明了它们的多样性和多功能性。然而，尽管基因调控也发生在细胞核和细胞质中，很少有人工 ODN 能够主动转运到细胞核中。在这项研究中，为了制备具有积累在细胞核能力的 ODN，我们将 Hoechst 分子引入到作为功能性分子载体到细胞核的 ODN 中（Hoe-ODN）。我们合成了 Hoe-ODN，并证实它们与 DNA 双链紧密结合。当将单链 Hoe-ODN 或由 Hoe-ODN 及其互补链组成的双链 ODN 施用于活细胞时，两种 ODN 都有效地积累在细胞核中。此外，与 Hoechst 单元连接的反义 ODN 被递送到细胞核中，并有效地抑制了其靶 RNA 的表达。因此，我们构建了一种能够将 ODN 转运到细胞核的输送系统。
