title: Targeted delivery of siRNA against hepatitis C virus by apolipoprotein A-I-bound cationic liposomes.
abstract: OBJECTIVE
  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 2mg 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.
authors.affiliation: Virus Research Laboratory, Mogam Biotechnology Research Institute, Giheung-Gu, Gyeonggi-Do, South Korea.
authors.forename: Soo In
authors.initials: SI
authors.lastname: Kim
authors.forename: Duckhyang
authors.initials: D
authors.lastname: Shin
authors.forename: Hyeon
authors.initials: H
authors.lastname: Lee
authors.forename: Byung-Yoon
authors.initials: BY
authors.lastname: Ahn
authors.forename: Yeup
authors.initials: Y
authors.lastname: Yoon
authors.forename: Meehyein
authors.initials: M
authors.lastname: Kim
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000494:pharmacology*; D002460:Cell Line; D016503:Drug Delivery Systems; D004355:Drug Stability; D005260:Female; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D008081:Liposomes / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis / Q000379:methods; D010957:Plasmids; D034741:RNA, Small Interfering / Q000737:chemistry / Q000494:pharmacology*; D014162:Transfection
chemical_list: D016632:Apolipoprotein A-I; D008081:Liposomes; D034741:RNA, Small Interfering