Intracellular Delivery of Antisense DNA and siRNA with Amino Groups Masked with Disulfide Units
| Autor: | Naoko Abe, Zhaoma Shu, Hiroshi Abe, Yuri Katsurada, Fumiaki Tomoike, Yukiya Takayama, Azumi Ota, Kosuke Kusamori, Makiya Nishikawa, Yoshihiro Ito, Seiichi Tada, Yasuaki Kimura, Kosuke Nakamoto |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Small interfering RNA Endosome Cell Transfection 010402 general chemistry 01 natural sciences DNA Antisense Cations Drug Discovery medicine Animals Humans Disulfides Gene Silencing Amines RNA Small Interfering Cytotoxicity Mice Inbred ICR 010405 organic chemistry Chemistry Oligonucleotide Cationic polymerization General Chemistry General Medicine 0104 chemical sciences medicine.anatomical_structure Drug delivery Biophysics Intracellular HeLa Cells |
| Zdroj: | Chemical and Pharmaceutical Bulletin. 68:129-132 |
| ISSN: | 1347-5223 0009-2363 |
| DOI: | 10.1248/cpb.c19-00811 |
| Popis: | Efficient methods for delivery of antisense DNA or small interfering RNA (siRNA) are highly needed. Cationic materials, which are conventionally used for anionic oligonucleotide delivery, have several drawbacks, including aggregate formation, cytotoxicity and a low endosome escape efficiency. In this report a bio-reactive mask (i.e., disulfide unit) for cationic amino groups was introduced, and the mask was designed such that it was removed at the target cell surface. Insolubility and severe cellular toxicity caused by exposed cationic groups are avoided when using the mask. Moreover, the disulfide unit used to mask the cationic group enabled direct delivery of oligonucleotides to the cell cytosol. The molecular design reported is a promising approach for therapeutic applications. |
| Databáze: | OpenAIRE |
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