Article
Inhibitory effect of small interfering RNA specific for a novel candidate target in PB1 gene of influenza A virus.
State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Xuanwu District, Beijing, PR China.
Journal of Drug Targeting (impact factor:
2.7).
01/2009;
17(2):133-9.
DOI:10.1080/10611860802473048
Source: PubMed
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Citations (0)
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Article: A novel ribozyme-based prophylaxis inhibits influenza A virus replication and protects from severe disease.
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ABSTRACT: Influenza A virus seasonal outbreaks and occasional pandemics represent a global health threat. The high genetic instability of this virus permits rapid escape from the host immune system and emergence of resistance to antivirals. There is thus an urgent need to develop novel approaches for efficient treatment of newly emerging strains. Based on a sequence alignment of representatives from every subtype known to infect humans, we identified nucleic acid regions that are conserved amongst these influenza A populations. We then engineered SOFA-HDV-Ribozymes as therapeutic tools recognizing these conserved regions to catalytically cleave the corresponding viral mRNA targets. The most promising ribozymes were chosen based on an initial in silico screening, and their efficacy was assessed using in vitro cleavage assays. Further characterization of their antiviral effect in cell culture and in mice led to the gradual identification of prophylactic SOFA-HDV-Ribozyme combinations, providing proof-of-principle for the potential of this novel strategy to develop antivirals against genetically highly variable viruses.PLoS ONE 01/2011; 6(11):e27327. · 4.09 Impact Factor
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Keywords
additional therapeutic target
antiviral effect
different methods
influenza virus infection
major concerns
marked decrease
new therapeutic options
overlapping gene
PB1-F2 gene
RNA
shared region
siRNA
urgent development
vaccines necessitates
virus infection
virus-associated cell apoptosis