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In vivo inhibition of influenza A virus replication by RNA interference targeting the PB2 subunit via intratracheal delivery.

In vivo inhibition of influenza A virus replication by RNA interference targeting the PB2 subunit via intratracheal delivery.
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Huang DT, Lu CY, Shao PL, Chang LY, Wang JY, Chang YH, Lai MJ, Chi YH, Huang LM,


Huang DT, Lu CY, Shao PL, Chang LY, Wang JY, Chang YH, Lai MJ, Chi YH, Huang LM, (click to view)

Huang DT, Lu CY, Shao PL, Chang LY, Wang JY, Chang YH, Lai MJ, Chi YH, Huang LM,

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PloS one 2017 04 0512(4) e0174523 doi 10.1371/journal.pone.0174523
Abstract
BACKGROUND
Influenza virus infection is a major threat to human health. Small interfering RNA (siRNA) is a promising approach for the prevention and treatment of viral infections. In this study, we constructed a series of DNA vector-based short hairpin RNAs (shRNAs) that target various genes of the influenza A virus using the polymerase III U6-RNA promoter to prevent influenza virus infection in vitro and in a mouse model.

RESULTS
Three sets of DNA vector-based shRNA, two targeting genes encoding the polymerase acidic protein (PA) and one targeting polymerase basic protein 2 (PB2), efficiently inhibited the replication of influenza virus A/WSN/33(H1N1) in vitro. We also successfully prevented influenza virus A/WSN/33(H1N1) infection in a C57BL/6 mouse model by intratracheal delivery of anti-PB2 shRNA.

CONCLUSIONS
Our findings suggest that the PB2-targeting shRNA plasmid showed potential for use as an RNAi-based therapeutic for influenza virus infection.

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