Alphavirus vectors: applications for DNA vaccine production and gene expression.
Replication-deficient alphavirus vectors have been developed for efficient high-level transgene expression. The broad host range of alphaviruses has allowed infection of a wide variety of mammalian cell lines and primary cultures. Particularly, G protein-coupled receptors have been expressed at high levels and subjected to binding and functional studies. Expression in suspension cultures has greatly facilitated production of large quantities of recombinant proteins for structural studies. Injection of recombinant alphavirus vectors into rodent brain resulted in local reporter gene expression. Highly neuron-specific expression was obtained in hippocampal slice cultures in vivo. Additionally, preliminary studies in animal models suggest that alphavirus vectors can be attractive candidates for gene therapy applications. Traditionally alphavirus vectors, either attenuated strains or replication-deficient particles, have been used to elicit efficient immune responses in animals. Recently, the application of alphaviruses has been extended to naked nucleic acids. Injection of DNA as well as RNA vectors has demonstrated efficient antigen production. In many cases, protection against lethal challenges has been obtained after immunization with alphavirus particles or nucleic acid vectors. Alphavirus vectors can therefore be considered as potentially promising vectors for vaccine production.
F. Hoffmann-La Roche, Research Laboratories, Basel, Switzerland. Kenneth.Lundstrom@roche.com
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D000524:Alphavirus / Q000235:genetics / Q000276:immunology; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D015316:Genetic Therapy; D005822:Genetic Vectors; D051379:Mice; D011994:Recombinant Proteins / Q000096:biosynthesis; D019444:Vaccines, DNA / Q000276:immunology; D014614:Vaccines, Synthetic
D000956:Antigens, Viral; D011994:Recombinant Proteins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic