In a controversial study in late 2011, Yoshihiro Kawaoka and Ron Fouchier altered the H5N1 viral genome and engineered a strain of the deadly virus capable of airborne spread between ferrets. The study sparked a debate about gain-of-function research with H5N1, with some experts raising concerns about the risks of accidental release and bioterrorism. What followed was a year-long voluntary moratorium on work with the H5N1 avian flu strain, lifted only earlier this year.
Now researchers at the Icahn School of Medicine at Mount Sinai, reporting in Nature Biotechnology, have developed a new âkill switch' security measure that could ensure safe research on the deadly gain-of-function influenza strains.
The research, led by Benjamin tenOever and Adolfo Garcia-Sastre, exploited the use of tiny non-coding microRNAs (miRNA) as âon-off' post-transcriptional regulators of gene expression. tenOever and Garcia-Sastre found that a specific miRNA, known as miR-192, was expressed in the lung cells of humans but not in those of ferrets. The team then altered the influenza A viral genome to incorporate a binding site for miR-192. As such, if the influenza A virus were to escape from the lab and enter the lung cells of a human, miR-192 would shut it down.
The team also showed the miRNA strategy worked with other influenza A viruses and believe it could theoretically work with any pathogenic virus. “It is clear that we can apply this technology to any virus,” said Dr. tenOever. “The only requirements are that we need a miRNA that is present in humans, but not in the model system where we want to study the virus, such as in ferrets. We also need a viral genome that permits insertion of miRNA target sites.”
The molecular biocontainment approach could prevent accidental spread of gain-of-function viruses and thus alleviate concerns associated with controversial gain-of-function influenza A research. Dr. tenOever said: "The question last year was whether the risk of altered bird flu escaping laboratories justified the science aimed at understanding the transmission of these viruses. With our method, the possibility of human transmission is no longer a concern."
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