Antisense therapy of influenza

Antisense oligonucleotides targeting the RNA binding region of the NP gene inhibit replication of highly pathogenic avian influenza virus H5N1

“…AS ODNs inhibit the influenza virus by interfering with viral gene expression in a sequence-specific manner. Previous studies of AS ODNs focused on the PA, PB1, NP and PB2 of the H1N1 influenza virus, and targeted the AUG initiation codon of viral genes [13,17,24].…”

“…They are potentially useful therapeutic agents for the treatment of viral diseases [13]. AS ODNs are effective against the influenza virus in vitro and in vivo by targeting the PA, PB2, NS1 and PB1 genes; these target sites are mainly focused on the conserved AUG initiation codon of the influenza virus [14][15][16][17]. There are no current studies of AS ODNs on the NP gene of H5N1 avian influenza.…”

Morpholino oligomers targeting the PB1 and NP genes enhance the survival of mice infected with highly pathogenic influenza A H7N7 virus

“…The currently available influenza drugs provide only partial therapeutic or prophylactic protection, and viral drug-resistance is a worsening problem (de Jong et al, 2005;Kiso et al, 2004;Le et al, 2005;Ludwig et al, 2003;McKimm-Breschkin, 2000). A variety of nucleic-acid based approaches have been reported as promising against influenza A virus (Abe et al, 2001;Ge et al, 2003Ge et al, , 2004aMcKimm-Breschkin, 2000;Plehn-Dujowich & Altman, 1998;Tado et al, 2001;Takahashi et al, 2004;Tompkins et al, 2004) and it appears that sequence-specific intervention in the influenza virus life cycle represents a promising avenue for drug development. Here, we show that PPMO targeting viral polymerase genes provide a useful strategy to inhibit highly pathogenic influenza virus infection in vivo.…”

Small RNAs targeting the 5′ end of the viral polymerase gene segments specifically interfere with influenza type A virus replication

“…The recent dissection of the RNA processing and control has opened up the frontiers to innovative concept of antiviral therapy based on nucleic acid RNA interference (DeVincenzo, 2012;Spurgers et al, 2008) cleotides as potential antivirals have already been used by different research groups for many pathogenic respiratory viruses (Spurgers et al, 2008;DeVincenzo, 2012), including the influenza virus (Wong et al, 2010). In this context, antivirals based on antisense oligonucleotides, small RNA interfering molecules and microRNAs (miRNA) targeting different sequences of influenza virus genome have been reported (Li et al, 2011;Kumar et al, 2013;Ge et al, 2006;Kwok et al, 2009;Abe et al, 2001;Duan et al, 2008). Influenza virus genomic segments encoding for the viral polymerase subunits (PA, PB1 and PB2), have been described to play a pivotal role in the hierarchy of segment interactions,during the packaging of viral genome into the newly assembled particles (Palese and Shaw, 2007;Hutchinson et al, 2010).…”