title: Antisense oligonucleotides directed against the viral RNA polymerase gene enhance survival of mice infected with influenza A.
abstract: We have investigated the ability of antisense phosphorothioate oligonucleotides to enhance the survival of mice infected with influenza A virus. The oligonucleotides were complementary to sequences surrounding the translation initiation codons of the viral PB2 or PA genes (PB2-as or PA-as, respectively) of the influenza A virus RNA polymerases. Intravenous administration of PB2-as in a complex with a cationic liposome, Tfx-10, significantly prolonged the mean survival time in days and increased overall survival rates of mice infected with the influenza A virus. Liposomally encapsulated PB2-as inhibited viral growth in lung tissues and reduced pulmonary consolidations. Liposomally encapsulated PB2-as could be an effective therapeutic agent against influenza A virus.
authors.affiliation: Rational Drug Design Laboratories, Makutsawa-Machi, Fukushima, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Mizuta
authors.forename: M
authors.initials: M
authors.lastname: Fujiwara
authors.forename: T
authors.initials: T
authors.lastname: Hatta
authors.forename: T
authors.initials: T
authors.lastname: Abe
authors.forename: N
authors.initials: N
authors.lastname: Miyano-Kurosaki
authors.forename: S
authors.initials: S
authors.lastname: Shigeta
authors.forename: T
authors.initials: T
authors.lastname: Yokota
authors.forename: H
authors.initials: H
authors.lastname: Takaku
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use; D001483:Base Sequence; D018387:Codon, Initiator; D017931:DNA Primers; D012321:DNA-Directed RNA Polymerases / Q000235:genetics*; D009980:Influenza A virus / Q000201:enzymology* / Q000302:isolation & purification; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D009929:Organ Size; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000821:virology; D012254:Ribavirin / Q000627:therapeutic use; D015996:Survival Rate; D013873:Thionucleotides / Q000627:therapeutic use*
chemical_list: D000998:Antiviral Agents; D018387:Codon, Initiator; D017931:DNA Primers; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; D012254:Ribavirin; D012321:DNA-Directed RNA Polymerases