Technologies
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WARF: P140264US02

Mutations That Improve Genetic Stability of Influenza Virus for Vaccination, Gene Therapy & More


INVENTORS -

Yoshihiro Kawaoka, Satoshi Fukuyama, Shinji Watanabe

The Wisconsin Alumni Research Foundation (WARF) is seeking commercial partners interested in developing novel mutations and methods of using them to enhance the stability of recombinant influenza virus, making it better suited for use in research, vaccines and gene therapy.
OVERVIEWThe influenza virus is a highly contagious respiratory pathogen that causes annual epidemics and occasional pandemics. Although many studies have looked at how a host responds to infection with the virus, the mechanisms of influenza virus-induced pathology are not yet fully understood. To analyze the immune response in vivo, viruses that express a fluorescent reporter protein have been created, but such viruses are significantly attenuated and the reporter gene is not stably maintained.

Influenza viruses also show strong potential as vaccine and gene delivery vectors. However, the influenza virus genome is so small that even relatively modest (~1 kb) fragments of foreign genes are unstable.
THE INVENTIONUW–Madison researchers have identified mutations in influenza virus gene segments that increase the stability and/or replication of the virus, particularly virus that contains a heterologous gene sequence. The mutations are found in the PA, PB1, PB2, NS and HA segments.

Recombinant influenza virus with one or more stabilizing mutations may be used as a vector for vaccines or gene delivery. In addition, the mutations allow influenza virus to stably maintain fluorescent reporter genes, making it possible to visualize the in vivo.
APPLICATIONS
  • Gene therapy
  • Vaccines
  • Research on influenza virus infection
KEY BENEFITS
  • Enhances stability and/or replication of influenza virus
  • Enables additional uses for recombinant influenza virus
  • Should be effective for influenza virus with any combination of hemagglutinin (HA) and neuraminidase (NA)
STAGE OF DEVELOPMENTStability, replication and virulence of influenza virus containing one or more of the mutations have been demonstrated in vitro and in vivo by intranasal inoculation in murine lung models.
ADDITIONAL INFORMATION
For More Information About the Inventors
Publications
  • Hanson H., Imai M., Hatta M., McBride R., Imai H., Taft A., Zhong G., Watanabe T., Suzuki Y., Neumann G., Paulson J. C. and Kawaoka Y. 2016. Identification of Stabilizing Mutations in an H5 Hemagglutinin Influenza Virus Protein. J. Virol. 90, 2981-2992.
Contact Information
For current licensing status, please contact Jennifer Gottwald at jennifer@warf.org or 608-960-9854.
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UW–Madison has the integrative capabilities to complete many key components of the drug development cycle, from discovery through clinical trials. As one of the top research universities in the world, and one of the two best-funded universities for research in the country, UW–Madison offers state-of-the-art facilities unmatched by most public universities.

These include the Small Molecule Screening Facility at the UW Comprehensive Cancer Center; the Zeeh Pharmaceutical Experiment Station, which provides consulting and laboratory services for developing formulations and studying solubility, stability and more; the Waisman Clinical Biomanufacturing Facility; the Wisconsin Institute for Medical Research, which provides UW–Madison with a complete translational research facility; and the innovative, interdisciplinary Wisconsin Institutes for Discovery, home to the private, nonprofit Morgridge Institute for Research and its public twin, WID, part of the university's graduate school. The highly qualified experts at these facilities are ready to work with you to create a library of candidates for drug development.