Incorporation of Antisense Oligonucleotides into Lipophilic Concatemeric Complexes Provides Their Effective Penetration into Cells
- 作者: Gusachenko O.1, Patutina O.1, Gvozdev V.1, Meschaninova M.1, Venyaminova A.1, Vlassov V.1, Zenkova M.1
-
隶属关系:
- Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
- 期: 卷 45, 编号 6 (2019)
- 页面: 739-748
- 栏目: Article
- URL: https://journals.rcsi.science/1068-1620/article/view/229321
- DOI: https://doi.org/10.1134/S1068162019060177
- ID: 229321
如何引用文章
详细
The development of highly effective molecular and biological tools to facilitate the penetration of therapeutic nucleic acids into cells opens a direct way to their successful application as drugs. It has been shown that the incorporation of single-stranded antisense oligonucleotides into concatemeric complexes enhances their binding to the membrane structures of eukaryotic cells, and the use of a cholesterol residue attached to one of the oligonucleotide strands considerably improves the delivery of concatemeric complexes of oligonucleotides to their intracellular target. In the present work, the efficiency of the formation of concatemeric structures from oligonucleotides carrying lipophilic fragments such as lithocholic acid, oleylamide of lithocholic acid, and cholesterol, attached to the 5′-end of the oligonucleotide through oligomethylene linkers of different length has been studied. It has been found that all modified oligonucleotides are capable of effectively “assembling” into concatemeric complexes; however, effective delivery into cells was observed only in the case of concatemeric complexes formed by oligonucleotides carrying a cholesterol residue attached through an aminohexanol linker. It has been shown that antisense oligonucleotides delivered to cells as part of these cholesterol-containing concatemeric complexes effectively inhibit the expression of the target gene.
作者简介
O. Gusachenko
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
Email: marzen@niboch.nsc.ru
俄罗斯联邦, Novosibirsk, 630090
O. Patutina
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
Email: marzen@niboch.nsc.ru
俄罗斯联邦, Novosibirsk, 630090
V. Gvozdev
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
Email: marzen@niboch.nsc.ru
俄罗斯联邦, Novosibirsk, 630090
M. Meschaninova
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
Email: marzen@niboch.nsc.ru
俄罗斯联邦, Novosibirsk, 630090
A. Venyaminova
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
Email: marzen@niboch.nsc.ru
俄罗斯联邦, Novosibirsk, 630090
V. Vlassov
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
Email: marzen@niboch.nsc.ru
俄罗斯联邦, Novosibirsk, 630090
M. Zenkova
Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of Sciences
编辑信件的主要联系方式.
Email: marzen@niboch.nsc.ru
俄罗斯联邦, Novosibirsk, 630090