Therapeutic and prophylactic applications of alphavirus vectors

Alphavirus vectors are high-level, transient expression vectors for therapeutic and prophylactic use. These positive-stranded RNA vectors, derived from Semliki Forest virus, Sindbis virus and Venezuelan equine encephalitis virus, multiply and are expressed in the cytoplasm of most vertebrate cells,...

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Bibliographic Details
Published in:Expert reviews in molecular medicine 2008-11, Vol.10, p.e33-e33, Article e33
Main Authors: Atkins, Gregory J, Fleeton, Marina N, Sheahan, Brian J
Format: Article
Language:English
Subjects:
Animals
Central Nervous System Diseases - drug therapy
Genes
Genetic Vectors
Genome, Viral
Mice
Molecular biology
Neoplasms - drug therapy
Neoplasms - prevention & control
Proteins
Ribonucleic acid
RNA
Semliki forest virus - genetics
Semliki forest virus - pathogenicity
Vaccines, Synthetic - administration & dosage
Virus Replication
Viruses
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Summary:Alphavirus vectors are high-level, transient expression vectors for therapeutic and prophylactic use. These positive-stranded RNA vectors, derived from Semliki Forest virus, Sindbis virus and Venezuelan equine encephalitis virus, multiply and are expressed in the cytoplasm of most vertebrate cells, including human cells. Part of the genome encoding the structural protein genes, which is amplified during a normal infection, is replaced by a transgene. Three types of vector have been developed: virus-like particles, layered DNA-RNA vectors and replication-competent vectors. Virus-like particles contain replicon RNA that is defective since it contains a cloned gene in place of the structural protein genes, and thus are able to undergo only one cycle of expression. They are produced by transfection of vector RNA, and helper RNAs encoding the structural proteins. Layered DNA-RNA vectors express the Semliki Forest virus replicon from a cDNA copy via a cytomegalovirus promoter. Replication-competent vectors contain a transgene in addition to the structural protein genes. Alphavirus vectors are used for three main applications: vaccine construction, therapy of central nervous system disease, and cancer therapy.
ISSN:1462-3994
1462-3994
DOI:10.1017/S1462399408000859