Targeted delivery of siRNA against hepatitis C virus by apolipoprotein A-I-bound cationic liposomes

Soo In Kim, Duckhyang Shin, Hyeon Lee, Byung Yoon Ahn, Yeup Yoon, Meehyein Kim

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Background/Aims: Hepatitis C virus (HCV) is one of the major human hepatic RNA viruses. Recently, we developed a liver-specific siRNA delivery technology using DTC-Apo composed of cationic liposomes (DTC) and apolipoprotein A-I (apo A-I). Here, we investigated whether DTC-Apo nanoparticles can systemically deliver siRNA into mouse hepatocytes expressing HCV proteins and inhibit their expression efficiently. Methods: A transient HCV model was constructed by hydrodynamic injection of plasmid DNA expressing viral structural proteins under hepatic control region and alpha1-antitrypsin promoter elements. Using this model, DTC-Apo containing HCV-core-specific siRNA was intravenously injected to assess antiviral activity as well as the duration of silencing. Results: Post-administration of DTC-Apo/HCV-specific siRNA at a dose of 2 mg siRNA/kg inhibited viral gene expression by 65-75% in the liver on day 2. Improved activity (95% knockdown on day 2) without immunotoxicity was obtained by 2′-OMe-modification at two U sequences on its sense strand. Notably, the gene silencing effect of the modified siRNA was still maintained at day 6, while the unmodified one lost RNAi activity after day 4. Conclusions: Our results suggest that DTC-Apo liposome is a highly potential delivery vehicle to transfer therapeutic siRNA especially targeting HCV to the liver.

Original languageEnglish
Pages (from-to)479-488
Number of pages10
JournalJournal of Hepatology
Volume50
Issue number3
DOIs
Publication statusPublished - 2009 Mar

Keywords

  • Apolipoprotein A-I
  • Hepatitis C virus
  • SR-BI
  • Systemic delivery
  • Tissue microarray
  • siRNA

ASJC Scopus subject areas

  • Hepatology

Fingerprint Dive into the research topics of 'Targeted delivery of siRNA against hepatitis C virus by apolipoprotein A-I-bound cationic liposomes'. Together they form a unique fingerprint.

  • Cite this