Alphavirus-Based Vectors

Alphavirus vectors have been developed for transient gene expression. The most common approach has been to generate replication-deficient vectors based on Semliki Forest virus, Sindbis virus, or Venezuelan equine encephalitis virus. All these alphavirus vectors have demonstrated efficient transduction of neurons in primary cultures, slices and in vivo. Wild-type vectors are cytotoxic resulting in host cell death. Mutant vectors have showed reduced toxicity and prolonged host cell survival. Engineering of temperature-sensitive mutants has allowed controlled expression and targeting to interneurons and astrocytes. Alphaviruses have been used in addition to neurobiology in drug discovery, structural biology, vaccine development, and cancer therapy.