Poxviruses Containing Novel Genes for PKR Inhibitors in place of E3L as Vaccine and Gene Therapy Vectors

Bertram Jacobs (Inventor)

Research output: Patent

Abstract

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 gene. These mutrated virus 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 and have decreased neurovirulence. These vectors can be used to protect against subsequent infection with vaccinia virus, and thus have utility in vaccination against various diseases.
Original languageEnglish (US)
StatePublished - Jan 2 2001

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Poxviridae
Active Immunotherapy
Genetic Therapy
Sequence Homology
Viruses
Genes
Plasmids
Vaccinia virus
DNA
Nose
Genetic Recombination
Vaccination
Vaccines
Research Personnel
Safety
Gene Expression
Lung
Brain
Infection

Cite this

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N2 - 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 gene. These mutrated virus 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 and have decreased neurovirulence. These vectors can be used to protect against subsequent infection with vaccinia virus, and thus have utility in vaccination against various diseases.

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