title: Inhibition of influenza virus in vivo by siRNA delivered using ABA triblock copolymer synthesized by reversible addition-fragmentation chain-transfer polymerization.
abstract: OBJECTIVE
  Influenza virus remains a major threat, with outbreaks continuing to occur. Few treatment options are available and drug resistance can emerge rapidly. New drugs that can quickly be adapted to virus mutations are needed. Several highly effective siRNAs targeting influenza that inhibit virus replication are known; however, effective delivery of these siRNAs remains a challenge. The aim of this study was to demonstrate the safety and efficacy of ABA triblock copolymer-delivered siRNA to inhibit influenza virus replication in vivo.
  
  
  METHODS
  We report on the delivery of a siRNA targeting the influenza virus in chicken embryos using an ABA triblock copolymer prepared by reversible addition-fragmentation chain-transfer polymerization, containing a central cationic block and two outer hydrophilic polyethylene glycol blocks.
  
  
  RESULTS
  A significant reduction of virus titer was observed with the polymer/anti-influenza siRNA complexes, whereas the control with polymer/control siRNA complexes showed no effect.
  
  
  CONCLUSIONS
  These data suggest that a reversible addition-fragmentation chain transfer-based siRNA delivery platform may be suitable for combating infectious diseases in vivo.
authors.affiliation: The Commonwealth Scientific & Industrial Research Organisation, Animal, Food & Health Sciences, Australian Animal Health Laboratory, 5 Portarlington Road, Geelong, VIC 3220, Australia.
authors.forename: Tracey M
authors.initials: TM
authors.lastname: Hinton
authors.forename: Arjun
authors.initials: A
authors.lastname: Challagulla
authors.forename: Cameron R
authors.initials: CR
authors.lastname: Stewart
authors.forename: Carlos
authors.initials: C
authors.lastname: Guerrero-Sanchez
authors.forename: Felix A
authors.initials: FA
authors.lastname: Grusche
authors.forename: Shuning
authors.initials: S
authors.lastname: Shi
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Bean
authors.forename: Paul
authors.initials: P
authors.lastname: Monaghan
authors.forename: Pathiraja A
authors.initials: PA
authors.lastname: Gunatillake
authors.forename: San H
authors.initials: SH
authors.lastname: Thang
authors.forename: Mark L
authors.initials: ML
authors.lastname: Tizard
mesh_terms: D000818:Animals; D002460:Cell Line; D002642:Chick Embryo; D015316:Genetic Therapy; D009975:Orthomyxoviridae / Q000235:genetics* / Q000502:physiology; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000628:therapy*; D058105:Polymerization; D011108:Polymers / Q000737:chemistry*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use*; D014779:Virus Replication
chemical_list: D011108:Polymers; D034741:RNA, Small Interfering
keywords: RAFT; influenza; polymerization; reversible addition-fragmentation chain transfer; siRNA