title: Inhibition of full length hepatitis C virus particles of 1a genotype through small interference RNA.
abstract: BACKGROUND
  Hepatitis C virus (HCV), a member of the Flaviviridae family of viruses, is a major cause of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Currently, the only treatment available consists of a combination of Pegylated interferon alpha (INF-α) and ribavirin, but only half of the patients treated show a sufficient antiviral response. Thus there is a great need for the development of new treatments for HCV infections. RNA interference (RNAi) represents a new promising approach to develop effective antiviral drugs and has been extremely effective against HCV infection.
  
  
  RESULTS
  This study was design to assess or explore the silencing effect of small interference RNAs (siRNAs) against full length HCV particles of genotype 1a. In the present study six 21-bp siRNAs were designed against different regions of HCV structural genes (Core, E1 and E2). Selected siRNAs were labeled as Csi 301, Csi 29, E1si 52, E1si 192, E2si 86 and E2si 493. Our results demonstrated that siRNAs directed against HCV core gene showed 70% reduction in viral titer in HCV infected liver cells. Moreover, siRNAs against E1 and E2 envelop genes showed a dramatic reduction in HCV viral RNA, E2si 86 exhibited 93% inhibition, while E1si 192, E2si 493 and E1si 52 showed 87%, 80%, and 66% inhibition respectively. No significant inhibition was detected in cells transfected with the negative control siRNA.
  
  
  CONCLUSIONS
  Our results suggested that siRNAs targeted against HCV structural genes efficiently silence full length HCV particles and provide an effective therapeutic option against HCV infection.
authors.affiliation: Division of Molecular Medicine, National Centre of Excellence in Molecular Biology, University of the Punjab, Lahore, Pakistan. usmancemb@gmail.com.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ansar
authors.forename: Usman Ali
authors.initials: UA
authors.lastname: Ashfaq
authors.forename: Imran
authors.initials: I
authors.lastname: Shahid
authors.forename: Muhammad Tahir
authors.initials: MT
authors.lastname: Sarwar
authors.forename: Tariq
authors.initials: T
authors.lastname: Javed
authors.forename: Sidra
authors.initials: S
authors.lastname: Rehman
authors.forename: Sajida
authors.initials: S
authors.lastname: Hassan
authors.forename: Sheikh
authors.initials: S
authors.lastname: Riazuddin
mesh_terms: D002460:Cell Line; D015536:Down-Regulation; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics* / Q000502:physiology; D006526:Hepatitis C / Q000188:drug therapy / Q000821:virology*; D006801:Humans; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics* / Q000627:therapeutic use; D014764:Viral Proteins / Q000235:genetics; D014779:Virus Replication
chemical_list: D034741:RNA, Small Interfering; D014764:Viral Proteins