Alphavirus vectors as tools in neuroscience and gene therapy

•Alphavirus-based expression can be utilized for RNA replicons, layered DNA/RNA expression vectors and recombinant virus particles.•Recombinant alphavirus particles provide highly efficient gene delivery to a broad range of host cells, primary neurons and Sindbis virus has demonstrated natural tumor targeting in vivo.•Semliki Forest virus has been evaluated for experimental autoimmune encephalomyelitis in a model for multiple sclerosis.•Protection against challenges with lethal doses of tumor cells have been observed after vaccination with alphavirus vectors expressing tumor antigens in animal models.•Alphavirus-based delivery of immunostimulatory, anti-cancer genes and micro-RNA sequences has demonstrated tumor regression and prolonged survival rates in animal models. Vectors in mammals.

Alphavirus-based vectors have been engineered for in vitro and in vivo expression of heterelogous genes. The rapid and easy generation of replication-deficient recombinant particles and the broad range of host cell infection have made alphaviruses attractive vehicles for applications in neuroscience and gene therapy. Efficient delivery to primary neurons and hippocampal slices has allowed localization studies of gene expression and electrophysiological recordings of ion channels. Alphavirus vectors have also been applied for in vivo delivery to rodent brain. Due to the strong local transient expression provided by alphavirus vectors a number of immunization and gene therapy approaches have demonstrated both therapeutic and prophylactic efficacy in various animal models.