title: Inhibition of hepatitis C virus genotype 3a by siRNAs targeting envelope genes.
abstract: Hepatitis C virus (HCV) genotype 3a is considered a significant risk factor for the development of liver diseases and hepatocellular carcinoma for most of the cases in Pakistan. Because of the limited efficiency of the current therapy, RNA interference (RNAi), which results in sequence-specific degradation of HCV RNA, has potential as a powerful alternative molecular therapeutic approach. The envelope genes (E1 and E2) of HCV come in immediate contact with cells during infection and therefore might be a relevant target for new drug development. In the present study, the expression of E1 and E2 genes of HCV genotype 3a was dramatically reduced at both the mRNA and protein level using gene-specific small interfering RNAs (siRNA) when compared to mock-transfected and cells treated with control siRNAs. The potential of siRNAs to inhibit HCV-3a replication in serum-infected Huh-7 cells was also demonstrated by combined treatment of siRNAs against the E1 and E2 genes, which resulted in a significant decrease in HCV viral copy number. This clearly demonstrates that the RNAi-mediated silencing of HCV E1 and E2 is among the first of its type for the development of an effective siRNA-based therapeutic option against HCV-3a.
authors.affiliation: Applied and Functional Genomics Laboratory, National Centre of Excellence in Molecular Biology, University of Punjab, Lahore 53700, Pakistan.
authors.forename: Saba
authors.initials: S
authors.lastname: Khaliq
authors.forename: Shah
authors.initials: S
authors.lastname: Jahan
authors.forename: Bushra
authors.initials: B
authors.lastname: Ijaz
authors.forename: Waqar
authors.initials: W
authors.lastname: Ahmad
authors.forename: Sultan
authors.initials: S
authors.lastname: Asad
authors.forename: Sajida
authors.initials: S
authors.lastname: Hassan
mesh_terms: D002460:Cell Line; D015870:Gene Expression; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics / Q000254:growth & development*; D006801:Humans; D008969:Molecular Sequence Data; D010154:Pakistan; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D012367:RNA, Viral / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics; D017422:Sequence Analysis, DNA; D014759:Viral Envelope Proteins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics
chemical_list: C087035:E1 protein, Hepatitis C virus; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012367:RNA, Viral; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus