MicroRNA-based strategy to mitigate the risk of gain-of-function influenza studies

Ryan A. Langlois, Randy A. Albrecht, Brian Kimble, Troy Sutton, Jillian S. Shapiro, Courtney Finch, Matthew Angel, Mark A. Chua, Ana Silvia Gonzalez-Reiche, Kemin Xu, Daniel Perez, Adolfo García-Sastre, Benjamin R. Tenoever

Research output: Contribution to journalArticlepeer-review

73 Scopus citations


Recent gain-of-function studies in influenza A virus H5N1 strains revealed that as few as three-amino-acid changes in the hemagglutinin protein confer the capacity for viral transmission between ferrets. As transmission between ferrets is considered a surrogate indicator of transmissibility between humans, these studies raised concerns about the risks of gain-of-function influenza A virus research. Here we present an approach to strengthen the biosafety of gain-of-function influenza experiments. We exploit species-specific endogenous small RNAs to restrict influenza A virus tropism. In particular, we found that the microRNA miR-192 was expressed in primary human respiratory tract epithelial cells as well as in mouse lungs but absent from the ferret respiratory tract. Incorporation of miR-192 target sites into influenza A virus did not prevent influenza replication and transmissibility in ferrets, but did attenuate influenza pathogenicity in mice. This molecular biocontainment approach should be applicable beyond influenza A virus to minimize the risk of experiments involving other pathogenic viruses.

Original languageEnglish (US)
Pages (from-to)844-847
Number of pages4
JournalNature Biotechnology
Issue number9
StatePublished - Sep 2013
Externally publishedYes

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Applied Microbiology and Biotechnology
  • Molecular Medicine
  • Biomedical Engineering


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