Antisense oligonucleotides directed against the viral RNA polymerase gene enhance survival of mice infected with influenza A.
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.
Mizuta
T
T
Rational Drug Design Laboratories, Makutsawa-Machi, Fukushima, Japan.
Fujiwara
M
M
Hatta
T
T
Abe
T
T
Miyano-Kurosaki
N
N
Shigeta
S
S
Yokota
T
T
Takaku
H
H
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*
D000998:Antiviral Agents; D018387:Codon, Initiator; D017931:DNA Primers; D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; D012254:Ribavirin; D012321:DNA-Directed RNA Polymerases