title: In vivo inhibition of influenza A virus replication by RNA interference targeting the PB2 subunit via intratracheal delivery.
abstract: BACKGROUND
  Influenza virus infection is a major threat to human health. Small interfering RNA (siRNA) is a promising approach for the prevention and treatment of viral infections. In this study, we constructed a series of DNA vector-based short hairpin RNAs (shRNAs) that target various genes of the influenza A virus using the polymerase III U6-RNA promoter to prevent influenza virus infection in vitro and in a mouse model.
  
  
  RESULTS
  Three sets of DNA vector-based shRNA, two targeting genes encoding the polymerase acidic protein (PA) and one targeting polymerase basic protein 2 (PB2), efficiently inhibited the replication of influenza virus A/WSN/33(H1N1) in vitro. We also successfully prevented influenza virus A/WSN/33(H1N1) infection in a C57BL/6 mouse model by intratracheal delivery of anti-PB2 shRNA.
  
  
  CONCLUSIONS
  Our findings suggest that the PB2-targeting shRNA plasmid showed potential for use as an RNAi-based therapeutic for influenza virus infection.
authors.affiliation: Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan.|Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Daniel Tsung-Ning
authors.identifier: http://orcid.org/0000-0001-6940-6701
authors.initials: DT
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Chun-Yi
authors.initials: CY
authors.lastname: Lu
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Pei-Lan
authors.initials: PL
authors.lastname: Shao
authors.affiliation: Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.|Department of Pediatrics, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Luan-Yin
authors.initials: LY
authors.lastname: Chang
authors.affiliation: Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan.
authors.forename: Jin-Yuan
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Yi-Hsuan
authors.initials: YH
authors.lastname: Chang
authors.affiliation: Department of Pediatrics, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Mei-Ju
authors.initials: MJ
authors.lastname: Lai
authors.affiliation: Institute of Biotechnology and Pharmaceutical Research, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Chi
authors.affiliation: Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan.|Department of Pediatrics, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Li-Min
authors.initials: LM
authors.lastname: Huang
mesh_terms: D000818:Animals; D005260:Female; D009980:Influenza A virus / Q000187:drug effects* / Q000502:physiology; D007442:Intubation, Intratracheal; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000517:prevention & control*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology*; D012324:RNA-Dependent RNA Polymerase / Q000187:drug effects*; D000067492:RNAi Therapeutics / Q000379:methods*; D014764:Viral Proteins / Q000187:drug effects*; D014779:Virus Replication / Q000187:drug effects
chemical_list: C057027:PB2 protein, Influenzavirus A; D034741:RNA, Small Interfering; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase