DNA such as plasmids or naked DNA, and other vectors, such as viral vectors and other poxviruses, have been used for the insertion into and expression from foreign genes. The basic technique of inserting foreign genes into live infectious poxvirus involves recombination between pox DNA sequences and homologous sequences present in donor plasmid and homologous sequences present in the rescuing pox-virus. A critical objective in vector development is to create so-called "attenuated vectors" for enhanced safety, so that the vector may be employed in an immunological or vaccine composition. It would, therefore, be an improvement over the state of the art to provide enhanced vectors such as vectors having enhanced transcription and/or expression which are attenuated, especially since attenuation may raise expression levels and/or persistence. Recent studies by researchers at Arizona State University have resulted in certain mutated poxviruses in which genes that code for certain inhibitors have been substituted for the poxvirus E3L or K3L genes. Such is the case in this present invention in which one or both of these genes have been replaced with a homologue of another virus. These mutated viruses have been found to replicate normally in cells but have exhibited decreased pathogenesis. These viruses replicate to high titers in nasal tissues, but have a decreased propensity to spread to the lungs and brain with dramatically decreased virulence. These vectors can be used to protect against subsequent infection with vaccinia virus, and thus have utility in vaccination against various diseases. This virus has been shown to inhibit the PKR enzyme making it extremely useful as a vaccine against smallpox and other diseases. It is also highly sensitive to treatment with interferon suggesting it will preferentially replicate in cancer cells.
|Original language||English (US)|
|State||Published - May 9 2002|