Inhibition of influenza virus replication in cultured cells by RNA-cleaving DNA enzyme.
Influenza virus replication has been effectively inhibited by antisense phosphothioate oligonucleotides targeting the AUG initiation codon of PB2 mRNA. We designed RNA-cleaving DNA enzymes from 10-23 catalytic motif to target PB2-AUG initiation codon and measured their RNA-cleaving activity in vitro. Although the RNA-cleaving activity was not optimal under physiological conditions, DNA enzymes inhibited viral replication in cultured cells more effectively than antisense phosphothioate oligonucleotides. Our data indicated that DNA enzymes could be useful for the control of viral infection.
Toyoda
T
T
Department of Virology, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka 830-0011, Japan. ttoyoda@supernig.nig.ac.jp
Imamura
Y
Y
Takaku
H
H
Kashiwagi
T
T
Hara
K
K
Iwahashi
J
J
Ohtsu
Y
Y
Tsumura
N
N
Kato
H
H
Hamada
N
N
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002384:Catalysis / Q000187:drug effects; D002460:Cell Line; D018387:Codon, Initiator / Q000235:genetics; D021881:DNA, Catalytic; D004277:DNA, Single-Stranded / Q000235:genetics / Q000378:metabolism*; D004285:Dogs; D006863:Hydrogen-Ion Concentration; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000378:metabolism; D009975:Orthomyxoviridae / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase; D012492:Salts / Q000494:pharmacology; D013379:Substrate Specificity; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics; D014779:Virus Replication
D018387:Codon, Initiator; D021881:DNA, Catalytic; D004277:DNA, Single-Stranded; D020319:Oligodeoxyribonucleotides, Antisense; C057027:PB2 protein, Influenzavirus A; D012333:RNA, Messenger; D012367:RNA, Viral; C402582:RNA-cleaving DNA 10-23; D012492:Salts; D014764:Viral Proteins; D012324:RNA-Dependent RNA Polymerase