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Nat Biotechnol. 2009 Jun;27(6):572-6. doi: 10.1038/nbt.1542. Epub 2009 May 31.

MicroRNA-mediated species-specific attenuation of influenza A virus.

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  • 1Microbiology Graduate School Training Program, Mount Sinai School of Medicine, New York, New York, USA.

Abstract

Influenza A virus leads to yearly epidemics and sporadic pandemics. Present prophylactic strategies focus on egg-grown, live, attenuated influenza vaccines (LAIVs), in which attenuation is generated by conferring temperature sensitivity onto the virus. Here we describe an alternative approach to attenuating influenza A virus based on microRNA-mediated gene silencing. By incorporating nonavian microRNA response elements (MREs) into the open-reading frame of the viral nucleoprotein, we generate reassortant LAIVs for H1N1 and H5N1 that are attenuated in mice but not in eggs. MRE-based LAIVs show a greater than two-log reduction in mortality compared with control viruses lacking MREs and elicit a diverse antibody response. This approach might be combined with existing LAIVs to increase attenuation and improve vaccine safety.

PMID:
19483680
[PubMed - indexed for MEDLINE]
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