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Therapeutic and prophylactic applications of alphavirus vectors

Published online by Cambridge University Press:  11 November 2008

Gregory J. Atkins ,
Marina N. Fleeton  and
Brian J. Sheahan
Gregory J. Atkins*
Affiliation:
Virus Group, Department of Microbiology, School of Genetics and Microbiology, Trinity College, Dublin 2, Ireland.
Marina N. Fleeton
Affiliation:
Virus Group, Department of Microbiology, School of Genetics and Microbiology, Trinity College, Dublin 2, Ireland.
Brian J. Sheahan
Affiliation:
Veterinary Sciences Centre, UCD School of Agriculture, Food Science and Veterinary Medicine, University College Dublin, Dublin 4, Ireland.
*
*Corresponding author: Gregory J. Atkins, Virus Group, Department of Microbiology, School of Genetics and Microbiology, Trinity College, Dublin 2, Ireland. Tel: +353 1 8961415; Fax: +353 1 6799294; E-mail: gatkins@tcd.ie
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Abstract

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.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 10 , October 2008 , e33
Copyright
Copyright © Cambridge University Press 2008

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References

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Further reading, resources and contacts

Lui, T.C. and Kirn, D. (2008) Gene therapy progress and prospects cancer: oncolytic viruses. Gene Therapy 15, 877-884Google Scholar
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