title: Small interfering RNAs targeting the rabies virus nucleoprotein gene.
abstract: Rabies virus (RABV) infection continues to be a global threat to human and animal health, yet no curative therapy has been developed. RNA interference (RNAi) therapy, which silences expression of specific target genes, represents a promising approach for treating viral infections in mammalian hosts. We designed six small interfering (si)RNAs (N473, N580, N783, N796, N799 and N1227) that target the conserved region of the RABV challenge virus standard (CVS)-11 strain nucleoprotein (N) gene. Using a plasmid-based transient expression model, we demonstrated that N796, N580 and N799 were capable of significantly inhibiting viral replication in vitro and in vivo. These three siRNAs effectively suppressed RABV expression in infected baby hamster kidney-21 (BHK-21) cells, as evidenced by direct immunofluorescence assay, viral titer measurements, real-time PCR, and Western blotting. In addition, liposome-mediated siRNA expression plasmid delivery to RABV-infected mice significantly increased survival, compared to a non-liposome-mediated delivery method. Collectively, our results showed that the three siRNAs, N796, N580 and N799, targeting the N gene could potently inhibit RABV CVS-11 reproduction. These siRNAs have the potential to be developed into new and effective prophylactic anti-RABV drugs.
authors.affiliation: Agricultural Division, College of Animal Science and Veterinary Medicine, Jilin University, Changchun 130062, Jilin Province, China.
authors.forename: Yu-Jiao
authors.initials: YJ
authors.lastname: Yang
authors.forename: Ping-Sen
authors.initials: PS
authors.lastname: Zhao
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
authors.forename: Hua-Lei
authors.initials: HL
authors.lastname: Wang
authors.forename: Hong-Ru
authors.initials: HR
authors.lastname: Liang
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Zhao
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Wu
authors.forename: Tie-Cheng
authors.initials: TC
authors.lastname: Wang
authors.forename: Song-Tao
authors.initials: ST
authors.lastname: Yang
authors.forename: Xian-Zhu
authors.initials: XZ
authors.lastname: Xia
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology; D001688:Biological Products / Q000008:administration & dosage* / Q000494:pharmacology; D002460:Cell Line; D006224:Cricetinae; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage; D005260:Female; D008081:Liposomes / Q000008:administration & dosage; D051379:Mice; D008807:Mice, Inbred BALB C; D009698:Nucleoproteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000494:pharmacology; D011818:Rabies / Q000188:drug therapy*; D011820:Rabies virus / Q000187:drug effects* / Q000235:genetics; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D001688:Biological Products; D004337:Drug Carriers; D008081:Liposomes; D009698:Nucleoproteins; D034741:RNA, Small Interfering