Synthesis and silencing properties of siRNAs possessing lipophilic groups at their 3'-termini.
Short-interfering RNAs (siRNAs) conjugated with lipophilic groups at their 3'-termini were synthesized. The properties of the synthesized siRNAs were examined in detail, and it was found that at low concentrations, their silencing abilities were dependent on the positions of the modifications and the types of organic molecules attached. Although the modification of siRNAs with palmitic acid or oleic acid at the 3'-end slightly reduced their silencing activities, siRNAs had enough abilities to induce RNAi at 10 nM concentrations. On the other hand, the modification of siRNAs with cholesterol at the 3'-end of the passenger strand was tolerated; however, the modification at the guide strand significantly reduces its silencing activity. The siRNAs modified with the lipophilic groups did not possess ability to penetrate the plasma membranes of HT-1080 cells without the transfection reagent. However, the results described in this report will aid in designing novel siRNAs with cell membrane-permeable molecules.
Ueno
Yoshihito
Y
Department of Biomolecular Science, Faculty of Engineering, Gifu University, Medical Information Sciences, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan. uenoy@gifu-u.ac.jp
Kawada
Koshi
K
Naito
Tomoharu
T
Shibata
Aya
A
Yoshikawa
Kayo
K
Kim
Hye-Sook
HS
Wataya
Yusuke
Y
Kitade
Yukio
Y
D015153:Blotting, Western; D002784:Cholesterol / Q000737:chemistry / Q000494:pharmacology; D004722:Endoribonucleases / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008055:Lipids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D009829:Oleic Acids / Q000737:chemistry / Q000494:pharmacology; D010169:Palmitic Acids / Q000737:chemistry / Q000494:pharmacology; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000138:chemical synthesis* / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D014162:Transfection
D008055:Lipids; D009829:Oleic Acids; D010169:Palmitic Acids; D034741:RNA, Small Interfering; D002784:Cholesterol; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease