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A new modified DNA enzyme that targets influenza virus A mRNA inhibits viral infection in cultured cells
Author(s) -
Takahashi Hitoshi,
Hamazaki Hiroyuki,
Habu Yuichiro,
Hayashi Mieko,
Abe Takayuki,
Miyano-Kurosaki Naoko,
Takaku Hiroshi
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(04)00073-0
Subject(s) - dna , nuclease , enzyme , deoxyribozyme , oligonucleotide , virus , biology , microbiology and biotechnology , influenza a virus , virology , rna , chemistry , biochemistry , gene
DNA enzymes are RNA‐cleaving single‐stranded DNA molecules. We designed DNA enzymes targeting the PB2 mRNA translation initiation (AUG) region of the influenza A virus (A/PR/8/34). The modified DNA enzymes have one or two N3′‐P5′ phosphoramidate bonds at both the 3′‐ and 5′‐termini of the oligonucleotides, which significantly enhanced their nuclease resistance. These modified DNA enzymes had the same cleavage activity as the unmodified DNA enzymes, determined by kinetic analyses, and reduced influenza A virus replication by more than 99%, determined by plaque formation. These DNA enzymes are highly specific; their protective effect was not observed in influenza B virus (B/Ibaraki)‐infected Madin–Darby canine kidney cells.