title: Protection against lethal vaccinia virus infection in mice using an siRNA targeting the A5R gene.
abstract: Although the World Health Organization has declared the eradication of smallpox in 1980, the fear of its potential use in bioterrorism has become a reality. Since the effectiveness of current vaccines and antiviral drugs is limited, development of new therapeutic strategies is needed. In this study, we investigated small interfering RNA (siRNA) as a therapeutic approach for preventing and treating smallpox infection.
  
  
  
  Eight siRNA sequences were designed and evaluated for antiviral activity against vaccinia virus (VACV) in vitro and in vivo.
  
  
  
  Of eight siRNAs, A5R1 siRNA targeted the A5R gene and reduced VACV replication in cell culture by up to 85% at 100 nM concentration without inducing cytotoxicity. A prolonged prophylactic as well as therapeutic effect of siRNA was observed. In addition, real-time PCR analysis showed that A5R1 siRNA can especially reduce the target mRNA. Finally, intraperitoneal delivery of A5R1 siRNA in Balb/c mice significantly protected these animals from lethal challenge with VACV.
  
  
  
  This study suggests the potential of A5R1 siRNA as a therapeutic antiviral agent against smallpox.
authors.affiliation: Department of Life Science, Sogang University, Seoul, Republic of Korea.
authors.forename: Dongjoon
authors.initials: D
authors.lastname: Seo
authors.forename: Na Young
authors.initials: NY
authors.lastname: Kim
authors.forename: Jin Ah
authors.initials: JA
authors.lastname: Lee
authors.forename: Kang Rok
authors.initials: KR
authors.lastname: Han
authors.forename: Gyeung Haeng
authors.initials: GH
authors.lastname: Hur
authors.forename: Jai Myung
authors.initials: JM
authors.lastname: Yang
authors.forename: Sungho
authors.initials: S
authors.lastname: Shin
mesh_terms: D000072283:A549 Cells; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002460:Cell Line; D004195:Disease Models, Animal; D015870:Gene Expression; D005814:Genes, Viral; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics* / Q000494:pharmacology / Q000627:therapeutic use*; D014615:Vaccinia / Q000517:prevention & control* / Q000821:virology; D014616:Vaccinia virus / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology; D010948:Viral Plaque Assay; D014779:Virus Replication / Q000187:drug effects / Q000235:genetics
chemical_list: D000998:Antiviral Agents; D034741:RNA, Small Interfering