title: Nucleic acid-mediated cleavage of M1 gene of influenza A virus is significantly augmented by antisense molecules targeted to hybridize close to the cleavage site.
abstract: Influenza A virus genome segment 7 encodes protein M1, which is the matrix protein playing crucial role in the virus life cycle. Any antiviral strategy that aims at reducing, in particular, the expression of this genome segment should, in principle, reduce the infectivity of the virus. We developed a specific antiviral approach at the molecular level and designed several novel 10-23 DNAzymes (Dz) and hammerhead ribozymes (Rz), specifically targeted to cleave at the conserved domains of the influenza virus M1 RNA. We sought to use antisense molecules with the hope that it will facilitate the ribozyme-mediated cleavage. We observed that the Mg(2+)-dependent sequence-specific cleavage of M1 RNA was achieved by both the Dz and Rz in a dose-dependent manner. This combination of catalytic Dz and Rz with antisense molecules, in principle, resulted in more effective gene suppression, inhibited the whole virus replication in host cell, and thus could be exploited for therapeutic purposes.
authors: Department of Respiratory Virology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi 110007, India.
authors: B
authors: B
authors: Kumar
authors: Madhu
authors: M
authors: Khanna
authors: P
authors: P
authors: Kumar
authors: V
authors: V
authors: Sood
authors: R
authors: R
authors: Vyas
authors: A C
authors: AC
authors: Banerjea
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D003001:Cloning, Molecular; D053837:DNA Cleavage / Q000187:drug effects*; D021881:DNA, Catalytic / Q000737:chemistry / Q000235:genetics; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000235:genetics; D004285:Dogs; D005434:Flow Cytometry; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D005814:Genes, Viral / Q000235:genetics*; D009980:Influenza A virus / Q000235:genetics*; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization / Q000187:drug effects*; D009696:Nucleic Acids / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D016337:RNA, Catalytic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014763:Viral Matrix Proteins / Q000378:metabolism*
chemical_list: D021881:DNA, Catalytic; D004277:DNA, Single-Stranded; C488936:M1 protein, Influenza A virus; D009696:Nucleic Acids; D016376:Oligonucleotides, Antisense; D016337:RNA, Catalytic; D012333:RNA, Messenger; C402582:RNA-cleaving DNA 10-23; D014763:Viral Matrix Proteins; C427204:hammerhead ribozyme