Synthesis and silencing properties of siRNAs possessing lipophilic groups at their 3′-termini

Yoshihito Ueno, Koshi Kawada, Tomoharu Naito, Aya Shibata, Kayo Yoshikawa, Hye Sook Kim, Yusuke Wataya, Yukio Kitade

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)7698-7704
Number of pages7
JournalBioorganic and Medicinal Chemistry
Volume16
Issue number16
DOIs
Publication statusPublished - Aug 15 2008

Keywords

  • Cholesterol
  • Oleic acid
  • Palmitic acid
  • RNAi
  • siRNA

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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